No retraction, correction or concern found when last checked on Oct 22, 2026.

Oxidative stress and the cardiovascular effects of air pollution

Mark R. Miller

Free Radical Biology and Medicine · 2020 · Review · CC BY

doi:10.1016/j.freeradbiomed.2020.01.004 (opens in a new tab)

Abstract

Cardiovascular causes have been estimated to be responsible for more than two thirds of the considerable mortality attributed to air pollution. There is now a substantial body of research demonstrating that exposure to air pollution has many detrimental effects throughout the cardiovascular system. Multiple biological mechanisms are responsible, however, oxidative stress is a prominent observation at many levels of the cardiovascular impairment induced by pollutant exposure. This review provides an overview of the evidence that oxidative stress is a key pathway for the different cardiovascular actions of air pollution.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 22, 2026. Paragraph numbers are ours, so an answer can point at one.

Abbreviations

1American Heart Association

2aryl hydrocarbon receptors

3blood brain barrier

4black carbon

5concentrated ambient particles

6carotid intima media thickness

7carbon monoxide

8carbon dioxide

9diesel exhaust

10diesel exhaust particulate

11electrocardiogram

12endothelin-1

13high density lipoprotein

14heart rate variability

15intercellular adhesion molecule-1

16low density lipoprotein

17lectin-like oxidized low density lipoprotein receptor

18N-acetylcysteine

19nicotinamide adenine dinucleotide phosphate oxidase

20N-methyl-d-aspartate

21nitric oxide

22nitrogen dioxide

23nitric oxide synthase

24ozone

258-oxo-2′-deoxyguanosine

26oxidized low density lipoprotein

27poly-aromatic hydrocarbons

28particulate matter

29particulate matter with a diameter <10 μm

30particulate matter with a diameter <2.5 μm

31sulphur dioxide

32superoxide dismutase

33vascular cell adhesion molecule-1

34von Willebrand factor

Introduction

35Air pollution has far-reaching consequences on biodiversity, and its impact on human health has moved this issue to the top ranks of the political agenda at an international level. Air pollution is the number one environmental risk factor for mortality and the fifth greatest risk factor for all-cause mortality, overall. Recently, it has been revealed that air pollution has effects throughout the body, however, its effects on the cardiovascular system, in particular, carry a disproportionate burden both in terms of morbidity and mortality. Indeed, due to high prevalence of cardiovascular disease globally and the intrinsic fatality of many cardiovascular conditions, more than two thirds of the mortality attributed to air pollution arise from cardiovascular causes, in particular ischaemic heart disease and cerebrovascular disease. Additionally, cardiovascular complications are likely to play important contributing roles to the action of air pollution in the progression of diseases in other organs.

36Great progress has been made in establishing the mechanisms underlying the cardiovascular effects of air pollution. It has become clear that oxidative stress plays a key role in the cardiovascular effects of many air pollutants. This topic was reviewed in detail in 2012, with the 2010–2016 data expertly reviewed in Kelly & Fussell 2017. This review is an amalgamation of previous evidence, together with more recent data (January 2016 to October 2019). By structuring the evidence into different facets of the cardiovascular pathophysiology, the intention is that this review will provide a comprehensive overview of role of oxidative stress in the cardiovascular effects of air pollution.

Air pollution

37Air pollution includes a vast range of substances derived from many different sources and chemical reactions within the atmosphere. A brief overview is given here, and readers are referred to accompanying papers in this special issue for further details. Airborne pollutants can arise from both natural sources (e.g. forest fires, volcanic eruptions, aerosolised soil and dusts, pollen and moulds) and anthropogenic sources (e.g. industry, power plants, traffic, household heating, cooking, construction, mechanical wear, agriculture, etc.). ‘Ambient’ air pollution refers to outdoor air pollution, and has received the greatest attention historically, although indoor sources of air pollution are gaining traction, especially in terms of the burden of disease in developing nations. The bulk of research into ambient air pollution tends to centre on urban air pollution due to, among other reasons, the high density of urban populations, greater levels of traffic-derived emissions and increasing urbanisation of societies worldwide.

38Urban pollution is a complex cocktail of chemicals. Gases such as sulphur dioxide (SO2), carbon dioxide (CO2), carbon monoxide (CO), ozone (O3) and nitrogen dioxide (NO2) are present in varying amounts. Gaseous pollutants have the potential to cause short- and long-term health effects, possibly in an additive manner to particulates. Many of these gases have oxidative properties, and induction of oxidative stress (together with inflammation) is a likely mechanism by which they can affect human health. Semi-volatile species such as benzene, naphthalene, formaldehyde, polyaromatic hydrocarbons (PAHs) exist as liquid droplets, but can also transition between gaseous and particulate phases of air pollution. Additionally, there are numerous sources of minute airborne particulate matter (PM). PM is categorised according to particle size. Coarse particles (PM10) are particles with a diameter of 10 μm or less, fine particles (PM2.5) have a diameter of 2.5 μm or less, and ultrafine particles (or “nanoparticles”) have a diameter of 100 nm or less (although precise definitions of these categories can be distinct in different disciplines). PM is monitored and regulated in the environment through stationary monitoring networks that measure PM10 and (slightly less frequently) PM2.5. It is not practically possible to widely measure ultrafine PM using monitoring networks in the environment at present. Elemental and organic carbon form a significant part of urban PM (especially that derived from combustion) but non-carbon constituents such as various mineral dusts, sea salt, ammonium, nitrates, sulfates, and others, are also present. The composition of particles is one of the key physiochemical properties determining the biological response to inhaled PM. Organic carbon species (PAHs, nitro-PAHs, alkanes, alkenes, alkyl-benzenes, quinones, etc.) and redox-active transition metals are frequently implicated in the health effects of urban PM, and the availability of these chemicals on the surface of PM influences the biological response to these particles.

39Particle size is also an important factor for the health effects of PM. Size is a determinant of the degree of penetration into the lung and ability (or inability) of biological clearance mechanisms to remove inhaled PM. Importantly, the size also has an immediate effect on the relative surface area of the PM, with small particles having a significantly greater surface area than the equivalent mass of a larger particle of the same material (although this is complicated somewhat by particle agglomeration in the air and in biological fluids). Accordingly, health associations are often greater and/or more consistent for PM2.5 than PM10. There is a general assumption that ultrafine particles could pose a greater risk to health due to their larger relative reactive surface area, and their ability to penetrate deep into the alveoli of the lungs and into the bloodstream. Vehicle exhaust is a prominent sources of ultrafine particles in urban PM, and diesel exhaust (DE) is of particular interest due to the greater proportion of ultrafine PM compared with gasoline/petrol engine emissions, as well as the tendency to be associated with high levels of co-pollutants such as NO2.

40Many of the above pollutants and their constituents have some capacity to induce health effects. However, in relation to the cardiovascular system, epidemiological associations tend to be more consistent for the particulate components. For this reason, this review will largely focus on the cardiovascular actions of PM and especially that of vehicle-derived emissions as prominent sources of ultrafine PM.

Air pollution and cardiovascular disease: overview of epidemiological evidence

41The cardiovascular effects of air pollution came to prominence in the early 1990s. In 1993, Dockery and colleagues examined the relationship between PM2.5 and hospital admissions/deaths from cardiovascular disease in six North American cities with broadly similar demographics. They found a strikingly linear relationship between levels of PM2.5 and cardiovascular morbidity and mortality (Fig. 1a). An adjusted mortality-rate ratio of 1.37 (95%CI: 1.11–1.68) was found for cardiopulmonary mortality between the least (11 μg/m3 PM2.5) and most (30 μg/m3 PM2.5) polluted cities. A later study by the group expanded this data to include 51 metropolitan areas throughout the USA. It was estimated that a decrease of 10 μg/m3 PM2.5 would increase average life expectancy by approximately 7 months. Furthermore, a 2007 study of more than 65,000 women in the USA demonstrated a 24% increase in risk of a cardiovascular event and an alarming 76% increase in the risk of death from cardiovascular disease. Lastly, a seminal study by Kunzli et al. showed a relationship between exposure to PM2.5 across Los Angeles, USA, and atherosclerosis (a chronic disease of the vasculature that underlies coronary artery disease and many other cardiovascular conditions). A difference of 10 μg/m3 PM2.5 was associated with a 4–6% increase in carotid-intima thickness (CIMT); a measure of atherosclerosis in the arteries of the neck that is predictive of disease in other vascular beds (Fig. 1b).

42Air pollution is associated with mortality and cardiovascular events (e.g. a heart attack or a stroke) in both the long- and short-term. Utilising data from three large US cohorts (359–500 thousand participants), Pope et al. demonstrated that long-term exposure to air pollution (1–4 years) was associated with an 8–18% increase in cardiovascular mortality per 30 μg/m3 PM2.5. An 8 year follow-up of ~5000 individuals found almost a doubling of the risk of cardiovascular mortality in individuals living in close proximity to a major road. In the short-term, increases in cardiovascular mortality and coronary events have been associated with ambient PM on the same and preceding day. The coronary effects of traffic-derived pollution may occur even earlier, as individuals presenting with myocardial infarction were more likely to have been in traffic 1–2 h beforehand.

43The dose-response relationship between PM and cardiovascular mortality still requires investigation, especially at low and high doses. Current evidence suggests that there is a linear relationship between moderate levels of PM and mortality, followed by a plateau in mortality rates at higher levels (“supralinear”). Importantly, relatively low levels of air pollution can promote cardiovascular disease long-term. Notably, these associations hold true for levels of PM2.5 that are currently below international guidelines (e.g. World Health Organisation; annual PM2.5 <10 μg/m3).

44The volume of epidemiological evidence stretches far beyond mortality and broad metrics of morbidity. Indeed, air pollution has been shown to be associated with most cardiovascular conditions, including coronary artery disease, cardiac arrhythmia and arrest, acute myocardial infarction, heart failure, cerebrovascular disease, peripheral arterial disease and venous thromboembolism. Comprehensive reviews of the mechanistic evidence for these associations have concluded that there is a strong case for causality between air pollution and a wide range of cardiovascular endpoints. This conclusion is concisely summarised in the seminal American Heart Associations (AHA) systematic reviews in 2004 and 2010: “evidence is consistent with a causal relationship between PM2.5 exposure and cardiovascular morbidity and mortality”. The weight of evidence has only been bolstered in the prevailing years. A 2015 expert position paper concluded that “There is now abundant evidence that air pollution contributes to the risk of cardiovascular disease and associated mortality, underpinned by credible evidence of multiple mechanisms that may drive this association”, stressing that “Air pollution should be viewed as one of several major modifiable risk factors in the prevention and management of cardiovascular disease”.

Oxidative stress in the cardiovascular effects of air pollution

45Oxidative stress has been cemented as a key pathway underlying the cardiovascular effects of air pollution. Both epidemiological studies and controlled exposure studies in human subjects have provided strong evidence for oxidative pathways and these foundations have been built upon by a network of mechanistic studies in animals and cellular models (expertly summarised in Ref.). The 2010 AHA statement concluded that “At a molecular level, oxidative stress as a critically important cause and consequence of PM-mediated cardiovascular effects has a sound experimental basis”. This review aims to be a comprehensive review of the role of oxidative stress in the cardiovascular effects of air pollution (for further information on the wider effects of PM-induced oxidative stress see Refs.). Studies have been identified that contain both an association between air pollution and cardiovascular function, and mechanistic evidence for oxidative stress (e.g. assessment of the oxidative potential of a pollutant, measurement of a biomarker of oxidative stress, identification of a source of free radicals, exploration of genetic polymorphisms conferring altered susceptibility to oxidative stress, or prevention/reversal with antioxidant compounds). The sheer volume of literature on this topic prohibits detailed critical analysis of individual assays, study designs and inconsistences. Nonetheless, all evidence in this overview is derived from peer-reviewed journals and expert book chapters. Furthermore, by structuring the review by different facets of cardiovascular system, it is clear that oxidative stress is a common, and important, mechanism in many of the different processes linking air pollution to cardiovascular mortality.

Vascular tone/endothelial dysfunction

46The tone of blood vessels is crucial to the distribution of blood around the body, and plays a key role in both the maintenance of homeostasis and the response to stimuli. Endothelial cells are the thin layer of cells that line the inner surface of blood vessels. The endothelium acts as an interface between the blood and vascular wall, both physically and through the synthesis and release of a range of active mediators. Endothelial dysfunction plays a key early role in vascular impairment and disease. Subsequently, the excessive contractility and loss of vasodilator responses caused by endothelial dysfunction are hallmarks of chronic cardiovascular disease.

47Epidemiology. In 2005 O'Neill et al. demonstrated that PM2.5 exposure was associated with a decreased in vasodilator response in the brachial artery of diabetic individuals. Subsequent evidence implicated oxidative stress as a potential mechanism. The reduction in brachial artery diameter to PM2.5 and black carbon (BC; used as an indicator for combustion-derived PM) in elderly individuals was associated with increased in plasma endothelin-1 (ET-1; a potent vasoconstrictor molecule) and oxidative stress (thiobarbituric reactive substances). Similar observations were made for the reduction in microvascular function in middle-aged and elderly individuals, that demonstrated that smaller arteries (which play a substantial role in blood pressure regulation, with high blood pressure ("hypertension") being a prominent risk factor of cardiovascular disease) were also narrowed by PM. Accordingly, PM exposure has been regularly associated with small, but significant, elevations in blood pressure. The hypertensive effect of air pollution is likely to be multifactorial in terms of both the contributing biological mechanisms and different air pollutants. A role for oxidative stress has been postulated by the nature of the pattern of vascular impairment induced by PM (Fig. 2). The oxygen free radical superoxide scavenges nitric oxide (NO), a key endothelial-cell derived mediator that controls vasodilatation of blood vessels. PM2.5 exposure was associated with impairment of both flow-mediated dilatation (endothelium-dependent) and vasodilation to nitroglycerin (an endothelium-independent NO-releasing vasodilator). This pattern of impairment (inhibition of vasodilators acting through NO) is suggestive of oxidative stress. A role for both oxidative stress and inflammation is supported by observations that the attenuation of flow-mediated dilatation in response to PM2.5 was greater in individuals with glutathione-S-transferase M1 polymorphisms, and associated with increases in myeloperoxidase. Similarly, healthy volunteers taken on a 1.5-h drive along a busy roadway showed diminished reactive hyperemia responses (a measure of endothelial-mediated vasodilatation) and reduced levels of plasma nitrite (a surrogate for endothelial NO). This effect was not apparent when cabin filters were used to lower particulate levels in the vehicle.

48Various blood and urine markers of oxidative stress are upregulated in participants with greater levels of PM exposure (e.g. Refs.). Additionally, personal monitoring of pollutants has been used to show that cumulative indoor and outdoor exposure to ultrafine particles is associated with oxidation of DNA in the blood. Traffic-related pollutants, specifically, appear to closely linked to circulating biomarkers of oxidative stress. Exposure to PM decreased endothelial-mediated dilatation in the microvasculature of elderly individuals in Los Angeles, USA. The degree of impairment was greatest for PM with characteristics of traffic-derived PM (black carbon and NO2) and was correlated with the oxidative potential of the PM in vitro.

49There is evidence that polymorphisms in antioxidant enzymes lead to a greater hypertensive response to pollutant exposure in comparison to those with the standard genetic alleles. In contrast, other studies have not found the associations between PM and vascular function/blood pressure to be accompanied by oxidative stress biomarkers or genetic status of antioxidant enzymes.

50There is a growing body of evidence linking air pollution to metabolic syndrome and diabetes; diseases that are frequently associated with cardiovascular complications, including microvascular dysfunction. While the associations between air pollution and diabetes are not discussed in detail in the current review, it is worthwhile noting that increases in both insulin resistance and biomarkers of oxidative stress were associated with air pollution exposure in children. Finally, ultrafine particles altered levels of endothelial progenitor cells (that are likely to be involved in the repair of endothelial damage) and leukocyte free radical production in non-smokers in Copenhagen.

51Controlled Exposure Studies. Controlled exposure studies in healthy volunteers have been vital in exploring the biological mechanisms of specific pollutants without many of the confounding variables of epidemiological studies. Controlled exposures to dilute diesel exhaust (DE) induced a compensatory increase in levels of antioxidants to the lung lining fluid as a response to the oxidative insult to the lungs, setting the scene for use of this approach to study the cardiovascular effects of pollutants. A 2-h inhalation of concentrated ambient particles (CAPs; ~150 μg PM/m3) and ozone (120 ppb) from the city of Toronto induced vasoconstriction of brachial arteries. A potential involvement of a systemic oxidative response was suggested by the greater levels of oxidation of the DNA of blood monocyte following controlled exposure to roadside ultrafine PM. A program of work by led by Newby and Mills utilised controlled exposures to identify the mechanisms by which exposure to DE impaired cardiovascular function. Their first study demonstrated that a 1-h exposure of DE (~300 μg PM/m3) caused a potent attenuation of vasodilator responses in the forearm. By utilising a series of different vasodilator infusions, they demonstrated that DE caused inhibition of endothelium-dependent vasodilatation (to acetycholine, bradykinin) and endothelium-independent NO donor drugs (to sodium nitroprusside), but not vasodilators that act independently of the NO pathway (verapamil) (see Fig. 2). This pattern of inhibition strongly supports a role for oxidative stress, as opposed to another means of vascular dysfunction such as non-specific damage to endothelial cells or de-regulation of vascular smooth muscle contractility (although other mechanisms such as down-regulation of the NO target enzyme, guanylate cyclase, could also be involved). This profile of vascular impairment was consistently observed in subsequent studies by these researchers. Inhalation of DE altered both antioxidant genes and genes regulating vascular homeostasis (e.g. vascular endothelial growth factor) in peripheral blood monocytes. Loss of endothelial NO-signalling contributed to the increased sensitivity to circulating ET-1 following acute exposure to DE. Controlled exposure to DE also impaired skin microvascular responses to endothelium-dependent vasodilators, but not an exogenous NO donor drug. Although the response to the NO donor drug was not altered, blood serum from volunteers induced the release of superoxide in cultured endothelial cells, the extent of which was related to the total dose of the volunteer received.

52Supplementation with antioxidant-rich fish oils have been found to limit the extent of endothelial dysfunction in response to controlled exposure to CAPs. Conversely, another study found that N-acetylcysteine (NAC), a compound with antioxidant properties (albeit it can also affect cell signalling through means unrelated for oxidative stress), promoted vasoconstriction to DE rather than prevented it. The reasons for this unexpected finding were not immediately apparent although could involve changes in vasoconstrictive eicosanoids or alterations in expression of basal antioxidants. The particulate components seem to drive the acute vascular effects of DE, and not gases such as NO2 or O3. In this regard, a recent study found that controlled exposure to higher concentrations of ozone increased blood levels ET-1, but actually decreased blood levels of nitrotyrosine (a marker of the reaction product of NO and superoxide).

53Animal models. Rodent models have been beneficial in exploring the mechanisms underlying the increased vasoconstriction/impaired vasodilation. The mechanistic evidence gathered by these studies provides strong evidence that oxidative stress may play a significant contributing role in mediating the impairments. Inhalation of DE in rats led to impaired endothelium-dependent relaxation in coronary arteries, an effect that could be reversed with superoxide scavengers. Two weeks exposure of rats to PM2.5 (albeit at high concentrations of 600 μg/m3) impaired pulmonary artery vasodilator function and decreased eNOS expression, in line with a compensatory increase in vascular superoxide dismutase (SOD; an enzyme which converts superoxide into oxygen and hydrogen peroxide). Interestingly, nitric oxide synthase (NOS; the enzymatic source of NO) inhibitors, or additional of NOS co-factors, prevented the impairment, suggesting that NOS uncoupling (causing generation of superoxide from NOS instead of NO) was an important mechanism. In support of this, sub-chronic exposure to PM2.5 led to depletion of the co-factors needed for the NO-generation from endothelial NOS. Other cellular sources of oxidative stress have been implicated. A role for nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) has been implicated in vascular impairment and elevated blood pressure induced by PM2.5 and diesel exhaust particulate (DEP). Exposure of rats to residual oil-fly ash caused rapid attenuation of relaxation responses in the microvasculature and adherence of myeloperoxidase-containing leukocytes to the vessel wall, suggesting that leukocytes enzymatically contributed to free radicals linked to the endothelial dysfunction.

54Oxidative stress also appears to play a role in the effects of PM exposure on circulating endothelial progenitor cells. Indeed, Haberzettl and colleagues demonstrated that CAPs inhalation in mice led to a plethora of mechanistic links between endothelial progenitor cells, vascular insulin resistance, inflammation and oxidative stress, building on the evidence that air pollution is associated with both cardiovascular disease and metabolic disease. The same group demonstrated that nine days inhalation of CAPs depleted circulating endothelial progenitor cells and led to an impaired angiogenic response (the growth of new blood vessels) in a mouse model of hind limb ischaemia. Mice overexpressing extracellular superoxide dismutase in the lung were protected against this effect, suggesting pulmonary oxidative stress has downstream consequences on the vasculature.

55In vitro experiments. Similarly to in vivo studies, isolated blood vessels directly treated with DEP also exhibit impaired endothelial-dependent vasodilatation and NO-mediated vasodilation, but not relaxations caused by NO-independent vasodilators. These findings provide support for the contention that if these particles reach the systemic circulation (by translocation from the lung into the pulmonary blood vessels) they could directly impair vascular function through oxidative stress without the need for prior interaction with the lung or inflammatory cells. Scavengers of oxygen free radicals and inhibitors of enzymatic sources of free radicals can prevent the direct vascular impairment induced by DEP (see Ref.). Albeit, the direct effect of PM on endothelial cells may be modest in comparison to that produced when the particles first interact with inflammatory cells.

56Direct exposure of isolated brain capillaries to DEP increased oxidative stress and inflammation; findings that may have implications for blood brain barrier integrity following inhalation of pollutants. Direct treatment of cultured endothelial cells with PM, DEP or motorcycle exhaust particles has also been shown to induce oxidative stress, alter endothelial cell signalling, upregulate adhesion molecules, down-regulate endothelial NOS and, ultimately, promote apoptosis. Finally, NAC has been shown to attenuate several effects of PM (e.g. inflammation and downregulation of NOS) in endothelial cells.

Atherosclerosis

57Endothelial dysfunction is an early initiating event in the vascular disease atherosclerosis. Loss of endothelial function and expression of adhesion molecules attracts and tethers circulating inflammatory cells to the vascular wall. Additionally, loss of NO and changes to endothelial cell phenotype encourage the oxidation of circulating lipids (e.g. low density lipoprotein (LDL) to oxidized LDL (oxLDL)) that are preferentially retained by inflammatory cells that begin to penetrate the damaged endothelial layer. The accumulation of both of inflammatory cells and lipids induces the formation of a fatty plaque in major arteries that grow into the lumen to impede blood flow. Erosion or rupture of advanced plaques is the trigger for thrombosis (a blood clot) that may occlude arteries causing a cardiovascular event such as a heart attack or stroke.

58Epidemiology. Individuals with greater exposure to PM (e.g. based on pollution monitoring data close to residential address, or distance of the residence from a major road) exhibit greater degrees of atherosclerosis, as assessed by a number of methods such as arterial wall thickness, coronary calcification (a marker of advanced plaques) and reduction of lumen diameter in the retinal microvasculature (which can be used as a non-invasive indicator of early atherosclerosis with prognostic value for cardiovascular outcomes). Exposure to ambient PM or BC has been associated with greater levels of inflammatory biomarkers and reduced antioxidant activity in the blood of elderly individuals with coronary artery disease. The narrowing of retinal blood vessels was associated with PM exposure, paralleled by increases in circulating levels of micro-RNA implicated with oxidative stress. Associations have been observed for CIMT and the oxidative capacity of PM10 collected in the year preceding the CIMT measurements.

59Occupational exposure to vehicle emissions (e.g. bus drivers and garagemen) led to greater levels of several markers of systemic oxidative stress in comparison to comparative controls. These included urinary 8-oxo-2′-deoxyguanosine (8-OH-dG; a marker of oxidative modification of DNA) and 15-isoprostanes, blood levels of protein carbonyls and nitrotyrosine, and lower levels of antioxidants in plasma. These observations were correlated to a number of pollutants, including PM10, PM2.5 and PAHs. There was no striking relationship with blood levels of LDL or high density lipoprotein (HDL), although the study did not measure oxLDL specifically. Nonetheless, a similar study found greater levels of oxLDL and decreased levels of antioxidants in the blood of taxi drivers. Furthermore, exposure to traffic-related air pollution in Shanghai, China, was associated with elevated levels of LDL. The effects on LDL were accompanied by increased blood pressure, indicators of insulin resistance and decreased antioxidant capacity. An interesting study by Wu et al. recruited students in Beijing before and after moving to a university campus with higher pollution levels. Increased exposure to PM2.5, especially PM rich in metals, led to higher oxLDL in the blood.

60The adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are involved in the attraction and tethering of leukocytes to the blood vessel wall, thus have a role in both early and on-going atherosclerosis. Exposure to PM2.5 increased levels of soluble VCAM-1 and ICAM-1 in the blood, an effect that was greater in individuals that are null for glutathione-S-transferase M1. Antioxidant-rich fish oils have been shown to reduce levels of the circulating vasoconstrictor ET-1 that are associated with PM2.5 exposure. Finally, extracellular vesicles carrying microRNA represent an emerging mechanism by which the pro-oxidative and pro-atherosclerotic effect of PM could be disseminated around the body.

61Controlled exposures in humans. The acute nature of controlled exposure studies in human subjects does not lend itself to studying the chronic development of atherosclerosis. However, it should be borne in mind that controlled exposure studies have been shown to have acute cardiovascular effects that will promote the development of vascular disease (see other sections of this review). Two controlled exposure studies were identified that specifically implicate oxidative stress in the atherosclerotic effects of air pollution. Controlled exposure of healthy subjects to DE increased plasma-soluble lectin-like oxidized low density lipoprotein receptor (LOX-1) levels, which would be expected to mediate, at least in part, the accumulation of lipids within the vascular wall. High density lipoprotein (HDL) acts to inhibit the oxidation of LDL, thus having a preventative action on the development of atherosclerosis. Controlled exposure to PM2.5, but not ozone, was shown to reduce the antioxidant activity of HDL in individuals with lower baseline HDL activity.

62Animal and in vitro models. Due to the long-term development of atherosclerosis in humans (over decades) and limited means to non-invasively measure atherosclerosis clinically, the availability of rodent models of atherosclerosis has been a boon for studying the mechanisms underlying atherosclerosis. The apolipoliprotein-E knockout and LDL receptor knockout mice have been especially useful in this regard, as advanced atherosclerotic plaques can develop in these mice in a few weeks if they are fed a high-cholesterol diet. A number of studies have now shown that exposure to PM or vehicle exhaust particles accelerate the development of atherosclerosis in these mice, both in terms of increasing plaque size and promoting plaque vulnerability to rupture (reviewed in Refs.). Oxidative stress has been implicated as a key mechanism for the pro-atherosclerotic effects of pollutants.

63PM and DE has been shown to oxidise LDL in vitro and in vivo. Furthermore, DEP exhibited synergistic effects with lipids on gene expression in cultured endothelial cells; an effect that was replicated by inhalation of ambient ultrafine PM in hypercholesterolaemic mice. PM-exposed atherosclerotic mice exhibited biomarkers of systemic oxidative stress in blood and urine, as well as alterations in antioxidant systems. Inhalation of vehicle exhaust increased levels of LOX-1 and dysfunctional HDL. The antioxidant and inflammatory pathways, nuclear factor erythroid-2 (Nrf-2) and aryl hydrocarbon receptor (AhR), played an interacting role in the atherosclerotic effects of air pollution. Furthermore, the plaques from PM-exposed mice have greater levels of markers of oxidative stress, demonstrated, for example, by nitrotyrosine staining (Fig. 3). Eight weeks inhalation of PM increased the thickness of coronary arteries in healthy rats, accompanied by upregulation of angiotensin pathways and decreases in hemogenase-1 levels. The role of gaseous versus particulate components of vehicle exhaust may have different effects on markers of oxidative stress and plaque composition.

64No research was found investigating the ability of antioxidant compounds to prevent the pro-atherosclerotic effects of pollutants. However, the antioxidant properties of selenium supplementation, was found to reduce both oxidative stress and VCAM-1 levels in healthy rats exposed to PM, which would be expected to influence the early stages of atherosclerosis.

Arrhythmia and heart rate variability

65Heart rate variability (HRV) is a set of parameters derived from detailed analysis of heart rhythm from electrocardiogram (ECG) recordings. These parameters are indicative of the modulation of the electrical activity of the heart, in particular, its regulation by the autonomic nervous system. For most HRV parameters, a reduction is would confer a greater risk of developing cardiovascular conditions (at a population level). The availability of low-cost non-invasive monitors to assess HRV has been readily employed to address the cardiac effects of air pollution, increasingly so in panel studies simultaneously measuring personal air pollution in real-time.

66Epidemiology. Although there is inconsistency between parameters and studies, overall, exposure to PM is associated with reduction in HRV (see Refs.). In students in Taipei, Taiwan, both PM10 and PM2.5 were associated with decreases in several HRV parameters, as well as increases in blood 8-OH-dG and C-reactive protein. Personal monitoring devices were also used to show associations between PM2.5 and HRV indices in Boston, USA, the effects of which were linked to urinary levels of 8-OH-dG. A series of US studies by Schwartz and colleagues demonstrated associations between PM2.5/traffic exposure and several HRV parameters. In many cases, alterations in HRV associated with PM2.5 were modified by genetic differences in antioxidant systems. Similar genetic susceptibility in antioxidant genes influenced associations between PM2.5 and corrected Q-T interval. In the interests of balance, others have failed to demonstrate clear links between air pollutants, HRV and oxidative biomarkers.

67Two groups have explored HRV during interventions to reduce exposure to air pollutants. Langrish et al. demonstrated that wearing an efficient facemask beneficially altered selected HRV parameters in patients with ischaemic heart disease walking alongside city-centre roads in Beijing, in comparison to performing the same walk without a mask. Laboratory analysis showed that the Beijing PM had a substantial capacity to generate superoxide free radicals. Also in Beijing, Lee and colleagues made measurements of HRV in residents during the 2008 Olympic Games when stringent measures were taken to reduce air pollution. While reduction of air pollution was shown to reduce levels of urinary markers of oxidative stress, HRV changes were inconclusive. The lack of clarity, however, could be explained by pollutant-specific effects as, while PM was reduced considerably, there were higher levels of ozone during this time. Dietary antioxidant supplementation, omega-3 fish oils in particular, was shown to limit the effects of air pollution on HRV in elderly individuals. Reductions in oxidative stress were also partially to account for the beneficial effects of statins in preventing the effects of PM2.5 on high-frequency HRV parameters.

68Controlled exposures in humans. A role for oxidative stress in the action of PM on HRV has been supported by controlled exposure studies. Acute exposure to ultrafine CAPs altered HRV and cardiac repolarization in patients with metabolic syndrome who were null for the glutathione S-transferase M1 allele, but not a comparative group from the general population. Controlled exposure to street air in Copenhagen was associated with reductions in HRV, although there were no consistent changes in various oxidative biomarkers. In contrast, Tong et al. found that exposure to CAPs reduced HRV in healthy volunteers, and this could be prevented by 4 weeks of oral omega-3 fatty acid supplements.

69Animal models. Several studies have addressed the cardiac effects of pollutants in rodents, demonstrating that PM can alter HRV via autonomic imbalance and alterations in baroreceptor sensitivity. Additionally, infusion of isoprenaline (isoproterenol) was used to promote arrhythmias, in rodent models. Five hours inhalation of CAPs in rats led to changes in ECG that were accompanied by increase in oxidative stress in cardiac tissue (although it should be noted that the assays used - chemiluminescence, thiobarbituric acid reactive substances – can also be increased by alteration in intermediary metabolism rather than oxidative stress). These effects could be prevented by inhibition of the renin-angiotensin system or pulmonary sensory receptors. The complex interplay between the oxidative stress and the autonomic system is highlighted by a study that demonstrated HRV changes to urban PM can be prevented by NAC, while the cardiac oxidative stress induced by the PM can be inhibited by blockade of the autonomic nervous system with beta-blockers. Pulmonary instillation of DEP to rats, prior to coronary artery ligation, increased the incidence of cardiac arrhythmia and the extent of myocardial infarction to the ischaemia induced by ligation. In this model, DEP-induced ischaemia induced greater levels of superoxide radical generation in the perfused heart. PM2.5 exposure to rats also induced changes in HRV and increased cardiac malondialdehyde, the effects of which were modified by co-exposure to ozone. Lastly, the prolongation of cardiac action potential and arrhythmias induced by pulmonary exposure to DEP were prevented by NAC.

Myocardial ischaemia and infarction

70Atherosclerosis of the coronary vasculature is the basis for ischaemic heart disease, where the restriction of blood flow leads to regions of cardiac ischemic that can manifest as angina. Occlusion of major coronary arteries can lead to prolonged ischaemia, resulting in death of the downstream myocardial cells resulting in myocardial infarction; fibrosis or death of regions of the heart leading to loss of cardiac function and obstruction to cardiac electrical conductance.

71Epidemiology. Exposure to traffic has been shown to increase the incidence of acute myocardial infarction in the subsequent hours. Additionally, hospital presentations/admissions for myocardial infarction were greater for those dwelling in areas of high air pollution. Long-term exacerbation of atherosclerosis and rupture of plaques will make a substantial contribution to the associations between myocardial infarction and exposure to air pollution. However, it is likely that many different cardiovascular effects of air pollution will act in concert to increase the susceptibility to cardiovascular events.

72Oxidative stress (raised levels of blood malondiadehyde) was found in patients with acute coronary events linked to black carbon exposure. Pekkanen et al. measured S-T segment depression (a region of an electrocardiogram representative of ischaemic stress in coronary arteries) in patients with stable coronary artery disease while exercising in the city of Helsinki, Finland. NO2, CO, PM2.5, particle number (used as a surrogate for ultrafine PM), but not coarse PM, were associated with an increased prevalence of S-T segment depression, with a lag of 2 days. The associations were stronger in those not taking beta-blockers, indicating that these effects may be more reflective of autonomic regulation of the heart rather than the coronary arteries, although oxidative stress was not specifically investigated as a mechanism in this study. Susceptibility to coronary events (cardiac mortality, non-fatal myocardial infarction, admission for unstable angina) has also been associated with black carbon exposure (used as a proxy for combustion-derived particles), with greater levels of malondialdehyde on admission to hospital. Furthermore, the oxidative potential of PM2.5 (and, to some degree, ozone co-exposure) related to the risk of myocardial infarction: particulates with the greatest oxidative potential were associated with ~8% increase in hospital admissions. NO2 exposure has been found to be associated with increased risk of acute myocardial infarction. The risk varied with polymorphisms of genes involved in glutathione pathways, although the investigators were not able to identify statistically significant changes in precise genes.

73Controlled exposures in humans. The greater sensitivity of the heart to ischaemic stress was demonstrated using controlled exposures to diesel exhaust. A 2 h exposure to 300 μg/m3 DE in patients with ischemic heart caused a two-fold increase in the extent of S-T segment depression induced in an exercise test (Fig. 4). This observation built on other work from this group showing that acute exposure to DE impaired vascular function through oxidative mechanisms.

74Animal models. Ligation of coronary arteries in rodents can be used to induce myocardial infarction to address the mechanisms responsible. Rats instilled with DEP prior to ligation were more prone to the resultant arrhythmia and likelihood of sudden death. Isolation of the heart afterward showed that the area of infarction was more than twice as large in rats exposed to DE than those that were non-exposed. Perfusion of the coronary blood vessel with a superoxide-sensitive spin-trap reagent demonstrated that there was an increase in free radical formation in the injured hearts of DE exposed mice. The antioxidant vanillic acid reduced the effects of PM10 on cardiac antioxidant levels, and partially improved mitochondrial disturbances after ischaemia reperfusion injury. Similarly, selenium supplementation decreased the oxidative action of PM2.5 in cardiac tissue in rats. Interestingly, 4 weeks inhalation of DE in healthy rats led to a broadly similar profile of cardiac gene expression (one linked with mitochondrial-derived oxidative stress) in healthy rats to that of air-exposed spontaneously hypertensive rats, suggesting DE induced similar cardiac changes to hypertension. Gaseous pollutants can also exert similar effects, with a 1–2 month exposure to ozone increasing ischaemia-reperfusion injury in rats that was characterised by increases in cardiac lipid peroxidation and decreased SOD activity. CO exacerbated myocardial injury and depletion of antioxidants in the heart of a rat model of myocardial infarction. The CO levels used were at the upper ranges of ambient levels in heavily polluted urban cities (30 ppm), spiked with peaks representative of that very close proximity to vehicle exhaust (100 ppm).

75In vitro experiments. Direct addition of DEP to cultured cardiomyocytes reduced contractile function, an effect that could be partially prevented by antioxidants. Similarly, PM2.5 that was known to reduce antioxidant capacity in mice, also caused decreased contractility of cardiomyocytes on direct exposure. Finally, the direct cytotoxicity or apoptotic effect of various PM in cardiomyocytes could be inhibited by compounds with antioxidant properties (e.g. NAC or diemethylthiourea, a scavenger of hydroxyl radicals and hydrogen peroxide). It should be noted that, due to the reaction kinetics of free radicals with antioxidants in comparison to that of other target molecules, the physiological relevance of the use of antioxidants as free radical scavengers in in vitro assays has been questioned.

Cardiac remodelling and heart failure

76Heart failure is the term used to describe the loss of the capacity of the heart as a result of long-term stress from coronary artery disease, prolonged high blood pressure, increased sympathetic drive, severe alterations in heart rhythm and damage to the heart from myocardial ischaemia, infarction or congenital defects and viral damage. It is characterised, ultimately, by a substantial loss of cardiac function so that the heart cannot deliver blood to meet the needs of the body. Hypertrophy (a remodelling and thickening of the cardiac wall) is common, whereby the heart attempts to compensate for the burden it is placed under, usually leading to a reduction in the efficiency of cardiac contractility and further pressure on the coronary arteries.

77Epidemiology. Exposure to air pollution has been associated with an increased incidence of heart failure. A meta-analysis of global data found that a number of air pollutants (PM10, PM2.5, SO2, NO2, CO, but not O3) were associated with an increase in relative risk for heart failure. PM2.5was associated with a 2.12% increase in risk per 10 μg/m3, and showed the greater persistence in terms of lag effect - the only pollutant to be associated with a significant effect 2 days later (longer lags were not investigated). Left ventricular mass (i.e. hypertrophy) was been found to be greater in those residing closer to major roads. These effects were magnified in those with polymorphisms for genes linked to inflammation and oxidative stress. Lastly, oxidative capacity of PM2.5 (via the dithiothreitol assay) showed stronger associations with hospital admissions for heart failure than PM2.5 (mass) alone (although it should be noted the dithiothreitol assay is imprecise and has generated conflicting results elsewhere).

78Animal models. PM2.5 exposure is associated with loss of cardiac contractility and increased collagen deposition in healthy rats. This study also demonstrated that the same exposure in rats with myocardial infarction produced a compensatory increase in glutathione in the cardiac tissue. PM2.5 induced pulmonary inflammation and oxidative stress alongside right ventricular hypertrophy in a mouse model of heart failure. An impressively intricate study by Wold et al. investigated the long-term effects of PM in a mouse model of heart failure, and cultured cardiomyocytes. Nine months exposure to PM2.5 (moderate levels of CAPs: ~80 μg/m3) led to an increase in blood pressure of 10 mmHg that was linked to a decreased ventricular contractility and remodelling, without an overall change in coronary flow reserve. Cardiomyocytes transitioned towards a fibrotic phenotype rather than contractile (Fig. 5), and these effects were paralleled by a decrease in plasma total antioxidant capacity. Although the value of the plasma total antioxidant capacity assay is debated, these observations could suggest that oxidative stress was involved in the processes of myocyte transition. PM2.5 exacerbated the effects of angiotensin-induced hypertension, leading to cardiac hypertrophy. These effects were mediated by RhoA/Rho-kinase signalling pathways, which the same group had previously shown to be involved in the hypertensive effects of PM2.5 via oxidative mechanisms. Wang et al. found that inhalation of PM2.5 induced left-ventricular dysfunction in mice. In this experiment, AMP-activated protein kinase (a protein involved in the sensing and regulation of cellular metabolism) was implicated in both the pro-fibrotic response and generation of oxidative stress. Left ventricular function has also been shown to be modified by 1–2 months ozone exposure; effects that were associated with lipid peroxidation in the heart, decreases in SOD activity and increases in cytokines.

Thombosis

79Blood clotting is needed to prevent excessive bleeding on injury. However, coagulation needs to be finely regulated, as excessive clotting increases the risk of cardiovascular conditions caused by thrombotic occlusion of arteries, e.g. at sites of atherosclerotic plaque rupture/erosion or through lodging of emboli (blood-borne thrombus) in smaller downstream arteries.

80Epidemiology. Thrombotic occlusion of arteries is the predominant cause of heart attacks and strokes. Several epidemiological studies have shown that air pollution, and especially PM exposure, is linked to atherothrombosis, thrombotic stroke and thromboembolism. A plethora of blood markers of pro-thrombotic pathways have been linked to PM exposure, including fibrinogen, tissue factor, von Willebrand factor (vWF), P-selectin and decreases in activity of fibrinolytic pathways the mediate clot breakdown (Fig. 6). Associations between several air pollutants and P-selectin have been shown to be accompanied by decreases in antioxidant levels in red blood cells. In students in Taipei, Taiwan, both PM10 and PM2.5 increased in blood 8-OH-dG, alongside increases in fibrinogen, C-reactive protein and the fibrinolytic inhibitor, plasminogen activator inhibitor-1. In contrast, personal measurement of PM2.5 in Copenhagen, Denmark, was associated with greater levels of oxidation of haemoglobin and plasma lipids, although there was no correlation between PM2.5 and blood fibrinogen levels. Also, while the use of various assays of oxidative potential of PM was found to have value for predicting pulmonary inflammation, there was only limited value in predicting biomarkers of coagulation.

81The composition of PM from five locations in the Netherlands has been explored in relation to thrombotic biomarkers. While PM composition did have an influence on biomarker levels, there was a less consistent relationship with the oxidative potential of the PM. A review of human studies concluded that the metallic components of PM are involved in its propensity to induce pro-thrombotic and oxidative biomarkers. Polyunsaturated fatty acids from fish oil have been shown to reduce blood fibrinogen associated with exposure to PM2.5.

82Controlled exposures in humans. Controlled inhalation of dilute DE in healthy volunteers increased blood coagulability in an ex vivo model of thrombosis to a damaged arterial wall in physiologically representative conditions. Activation of platelets and platelet-monocyte binding were proposed as the driving mechanism for the increased coagulability, however, the authors speculate a role for oxidative stress and inflammation in the activation of platelets and vascular dysfunction observed in a parallel study with showing increased thrombosis to DE. A separate group of researchers demonstrated that DE alters the expression of several antioxidant pathways in peripheral blood monocytes, supporting a role for systemic oxidative stress in the cardiovascular actions of DE. Another gene profiling study found that inhalation of DE was associated with changes in pathways of both coagulation and oxidative stress/inflammation, including Nrf-2 pathways and inducible forms of NOS. Additionally, controlled exposures to CAPs increased blood plasminogen and markers of acute phase response in individuals with genetic deficiencies in various antioxidant systems. In contrast, a study of young healthy individuals asked to spend 5-h at locations with varying PM levels did not find an association between vWF and the in vitro oxidative potential of the different PM.

83Animal models. Pulmonary exposure to PM and DE have also been shown to upregulate vWF and tissue factor, and downregulate fibrinolytic pathways, in rodent models. These changes were associated with alterations in haemoxygenase-1 and LOX-1 pathways. Pulmonary instillation of urban PM or DEP has been shown to accelerate thrombosis at sites of large vessel injury. In contrast, Nemmar and colleagues found an increase in tail bleeding time (potentially indicating a decrease in thrombogenecity) following pulmonary instillation of DEP. The authors speculate that this could be due to decreases in circulating platelet numbers in response to DEP. Nonetheless, a follow-up study found that DEP instillation increased thrombosis in cerebral arterioles after photochemical injury. The changes were accompanied by reduction in antioxidant activity, and could be reversed by compounds with antioxidant properties. The pro-thrombotic effect of DEP in arterioles of a diabetic mouse model were linked to a combined action of increased platelet activation, decreased fibrinolytic activity, systemic inflammation and oxidative stress. Lastly, redox-active transition metals in PM from Mexico City were linked to prothrombotic and anti-fibrinolytic effects in the rat lung. The surface chemistry of the insoluble particulate, rather than the aqueous soluble compounds that can leach from the PM, played a greater contribution to these effects.

84In vitro experiments. Direct addition of PM to whole blood has been used to test to the pro-thrombotic potential of particles. The concentrations used in these experiments are likely to be beyond that expected to reach the circulation after inhalation in the real world. Nonetheless, broad insights into the relative potencies of different PM and potential mechanisms may be garnered. Soluble extracts of oil-fly ash containing PM were able to directly promote thrombosis, the extent of which was dependent on metal content of the PM. These effects could be reduced by complexing iron, suggesting that Fenton-derived hydroxyl free radicals could be a potential mechanism. A similar observation has been shown for a US urban PM standard reference material. Free-radical generating capacity of PM was linked to the prothrombotic phenotype of endothelial cells in an in vitro model of endothelial-fibrin-clot binding. Direct administration of DEP increased blood coagulation in vitro, which could be prevented with the antioxidant/anti-inflammatory agent, emodin. Treatment of cultured endothelial cells with ultrafine PM from Chapel Hill, USA, promoted the ability of these cells to generate active thrombin from a substrate, an effect that was reversed by SOD and catalase, or diphenyleneiodonium (a flavoprotein inhibitor that may act through inhibition of NAD(P)H-oxidase).

Stroke

85Stroke is caused by ischaemia in the brain that results in sensorimotor impairments and potentially damage to the brain or dementia. Stroke can be categorised by the cause of the ischaemia; ischaemic stroke caused by atherothrombotic occlusion with the arteries within the brain or those leading to the brain (e.g. the carotid arteries), or haemorrhagic stroke caused by rupture of the cerebral blood vessels and bleeding out into the brain. In either case, ischaemia triggers a cascade of pathophysiological changes in the cells of the affected area, and oxidative stress is a key feature of both the ischaemia and damage caused by sudden reperfusion of the tissues should it occur.

86Epidemiology. There is a wealth of epidemiological evidence showing the exposure to air pollution is associated with increased hospital admission for stroke in different regions of the world. Associations for PM tend to be more consistent than those for gaseous co-pollutants (Fig. 7) and are observed at levels of air pollution below many guideline levels. However, the role of oxidative stress in these associations has received little attention in epidemiological studies. Although direct evidence is lacking, it has been postulated that free radical generation from PM promotes stroke through increased inflammation and blood coagulability, which accords with the stronger associations between air pollution and ischaemic stroke rather than haemorrhagic stroke. While not necessarily stroke per se, a Swiss study investigated air pollution and oxidative stress in blood samples from non-smoking patients collected within 17 years prior to their diagnosis with cerebrovascular disease. In this study, PM2.5 and NO2 were all associated with methylation of genes linked to oxidative stress and inflammation.

87Animal models. While it is challenging to fully reproduce the causes and consequences of stroke, in vivo and in vitro models have provided evidence to suggest that air pollution would exacerbate stroke, with oxidative stress being an anticipated mechanism. Roadside ultrafine PM, with a known ability to generate free radicals in vitro, was shown to alter glutamate signalling and cytokine release in the brain following inhalation in rats. Upregulation of haemoxygenase expression was observed in the brain after instillation of PM10 in mice. The effects of PM on the brain have been associated with levels of transition metals in PM, potentially suggesting a role for metal-derived free radical generation. Oil-combustion PM was shown to cause marginally greater changes in oxidative stress markers in the lungs and heart of stroke-prone hypertensive rats, in comparison to either healthy or hypertensive rats that are not prone to stroke. Oxidative stress was proposed to play a contributing role in disruption of the blood brain barrier after inhalation of vehicle exhausts. Indeed, photochemical induction of thrombosis in cerebral microvessels was exacerbated by pulmonary exposure to DEP; an effect that could be prevented by co-administration of an antioxidant cysteine pro-drug.

88In vitro experiments. Cells within the central nervous system are considered to have a lower reserve of antioxidants in comparison to many other cell types. Cultured neuronal cells and microglial (the macrophage-like cell of the nervous system) have been used to show that PM can induce oxidative stress and cytotoxicity. Free radical generation from roadside PM regulated N-methyl-d-aspartate (NMDA) channels (implicated in hypoxic neuronal damage) in cultured neuronal and glial cells. Similar observations have been found for the direct action of DEP on dopamine signalling in PC-12 cells (used as a model for neural differentiation). Additionally, periods of ischaemia can be induced in cultured brain slices leading to molecular changes that have representative features of the response to cerebral ischaemic in vivo. Application of these tissue preparations with various types of PM can induce cellular-molecular changes characteristic of the response to stroke (e.g. alterations in NMDA channel activity, dopaminergic and glutamatergic disruption). In many cases, such effects are associated with inflammation and oxidative stress (see Ref.).

89Primary cultures of microvascular cells can be used to model cerebral arteries. Generation of reactive oxygen species are a prominent mechanism by which DEP can impair the function of endothelial cells that line the inner surface of such arteries. These cells represent a potential early target in the disease processes underlying cerebrovascular disease. Direct exposure of DEP to isolated brain capillaries increased oxidative stress and inflammation, and may alter blood brain barrier permeability. While there is debate as to whether inhaled particles can access the brain in sufficient numbers, and penetrate throughout cerebral tissue, these in vitro findings offer a means by which inhalation of (the smallest ultrafine) particles could confer increased susceptibility to the consequences of a stroke.

Conclusions

90Awareness of health effects of air pollution is increasing globally, and has now become a priority issue on the environmental, health and political agenda. This awareness has been bolstered by global data revealing the staggering magnitude of the health effects of pollution; culminating in annual mortality rates in excess of several million people. Additionally, over the last three decades, a formidable body of scientific evidence on the underlying biology has grown to support a case for causality in the health effects of air pollution. A crucial stimulus for action has been the wider recognition that the effects of air pollution are not confined to the lung, but instead have effects in what appears to be every organ of the body. The cardiovascular effects of pollution are increasingly gaining mainstream recognition. Given the high incidence of cardiovascular disease worldwide, and the high mortality rates that accompany it, the effects of pollution on the cardiovascular system will remain of key importance. Furthermore, now there is robust human evidence that inhaled nanoparticles may enter the bloodstream, the circulation is not only a means to deliver translocated particles throughout the body, but also the direct action of pollutants on the cardiovascular function could contribute to the effects of air pollution on different organs of the body (e.g. through hypertension, impaired perfusion of organs, alterations in vascular growth, etc.).

91Substantial progress has been made in determining the biological mechanisms for the cardiovascular effects of air pollution. A host of interacting mechanisms has been revealed, however, oxidative stress represents a key mechanism for the pathophysiological actions of pollution on the different facets of the cardiovascular system (Fig. 8). It is notable that oxidative stress emerges as a mechanism in the cardiovascular actions of pollutants using different research approaches; across epidemiological studies, controlled exposures in man, animal models and in vitro preparations. Clearly there are inconsistencies in evidence and, even before publication bias, studies will inevitably favour positive results over negative findings (and it should be acknowledged that this is also true to a degree in the present review too). Nonetheless, the sheer scale of the high-quality research, with complementary findings across multiple endpoints and study types, would argue that oxidative stress is a crucial mechanism underlying the link between air pollution and cardiovascular disease. Whether or not oxidative stress is the key initiating event, or only a contributing factor, is challenging to address, however, its presence will undoubtedly exacerbate disease. The close interplay between oxidative stress and inflammation represents a likely means by which the actions of air pollution can be amplified to produce pathophysiological effects in multiple organs. Furthermore, given the clear pro-oxidative effects of many pollutants, and capacity for oxidative stress to impair multiple aspects of cardiovascular function, oxidative stress is likely to play a key mediating role, as opposed to simply being an epiphenomenon of the later stages of disease.

92Reducing of the sources of pollution should be the key strategy to alleviate the burden of air pollution on health. However, given the challenges faced in lowering anthropogenic pollution in the face of increasing urbanisation, and the inevitably sluggish progress in implementing political and lifestyle changes, there is a place for interventions that can protect against pollution in the intervening time. Medicines should not be a first-line strategy to prevent the effects of pollution, however, this does not mean that such interventions should be dismissed entirely, especially for those that may be at greater risk (e.g. the young, elderly, those with pre-existing cardiorespiratory disease, and those that have an unavoidable high exposure to pollutants). The consistency of the evidence for a role of oxidative stress in the actions of air pollution raises the potential for the use of antioxidant compounds to ameliorate the actions of exposure to pollutants. This is especially the case given that dietary changes can be a simple means to increase antioxidant intake. While vitamin supplements have largely fallen out of favour given the disappointing large-scale trials with cardiovascular endpoints, it should not be forgotten that these supplements are readily-available, low cost and largely innocuous, and there is substantial scientific evidence supporting their potential to lessen aspects of disease. Indeed, this review highlights several preclinical studies (see also work by Nemmar et al. e.g. Ref.), as well as a few small panel studies whereby antioxidants can prevent the cardiovascular effects of air pollution. Of note, a recent study of over half a million subjects in the USA demonstrated that a Mediterranean diet rich in antioxidants (higher proportion of fruit and vegetables, olive oil, oily fish and moderate consumption of alcohol (e.g. antioxidant-rich red wine)) led to a reduction in the rates of cardiovascular mortality (from ischaemic heart disease, cardiac arrest and stroke) associated with PM2.5 and NO2 exposure. Polyunsaturated fatty acids from fish oil have also been shown to increase antioxidant enzyme levels and decrease peroxidised lipid/lipoproteins in the blood, as well as ameliorate the effects of PM2.5 on HRV, blood fibrinogen, plasma inflammatory markers and endothelin-1. Similar positive effects of fish oils have been found for endothelial dysfunction caused by controlled exposure to PM2.5. Further large scale studies in human volunteers are needed to ascertain if this approach has merit as an adjunct to strategies to reduce pollutants.

93In conclusion, oxidative stress is a key mechanism by which exposure to air pollution causes cardiovascular morbidity and mortality. Strategies that reduce air pollutants would be expected to reduce the burden of cardiovascular disease, and potentially other associated health conditions driven by oxidative pathways.

Declaration of competing interest

94The author has no conflicts of interest to declare.

References 261

1.
Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015 · 2017
Corrected
2.
Schraufnagel D.E., Balmes J.R., Cowl C.T., De Matteis S., Jung S.H., Mortimer K., Perez-Padilla R., Rice M.B., Riojas-Rodriguez H., Sood A., Thurston G.D., To T., Vanker A., Wuebbles D.J. Air pollution and noncommunicable diseases: a review by the forum of international respiratory societies' environmental committee, Part 1: the damaging effects of air pollution. Chest. 2019;155:409-416.
Not in our library10.1016/j.chest.2018.10.042 (opens in a new tab)
3.
Schraufnagel D.E., Balmes J.R., Cowl C.T., De Matteis S., Jung S.H., Mortimer K., Perez-Padilla R., Rice M.B., Riojas-Rodriguez H., Sood A., Thurston G.D., To T., Vanker A., Wuebbles D.J. Air pollution and noncommunicable diseases: a review by the forum of international respiratory societies' environmental committee, Part 2: air pollution and organ systems. Chest. 2019;155:417-426.
Not in our library10.1016/j.chest.2018.10.041 (opens in a new tab)
4.
Lelieveld J., Klingmuller K., Pozzer A., Poschl U., Fnais M., Daiber A., Munzel T. Cardiovascular disease burden from ambient air pollution in Europe reassessed using novel hazard ratio functions. Eur. Heart J. 2019;40:1590-1596.
Not in our library10.1093/eurheartj/ehz135 (opens in a new tab)
5.
Miller M.R., Newby D.E. Air pollution and cardiovascular disease: car sick. Cardiovasc. Res. Oct 2019.
Not in our library10.1093/cvr/cvz228 (opens in a new tab)
6.
Raftis J.B., Miller M.R. Nanoparticle translocation and multi-organ toxicity: a particularly small problem. Nano Today. 2019;26:8-12.
Not in our library10.1016/j.nantod.2019.03.010 (opens in a new tab)
7.
Miller M.R., Shaw C.A., Langrish J.P. From particles to patients: oxidative stress and the cardiovascular effects of air pollution. Future Cardiol. 2012;8:577-602.
Not in our library10.2217/fca.12.43 (opens in a new tab)
8.
Kelly F.J., Fussell J.C. Role of oxidative stress in cardiovascular disease outcomes following exposure to ambient air pollution. Free Radic. Biol. Med. 2017;110:345-367.
Not in our library10.1016/j.freeradbiomed.2017.06.019 (opens in a new tab)
9.
Brook R.D., Rajagopalan S., Pope C.A., Brook J.R., Bhatnagar A., Diez-Roux A.V., Holguin F., Hong Y., Luepker R.V., Mittleman M.A., Peters A., Siscovick D., Smith S.C., Whitsel L., Kaufman J.D. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation. 2010;121:2331-2378.
Not in our library10.1161/cir.0b013e3181dbece1 (opens in a new tab)
10.
Auerbach A., Hernandez M.L. The effect of environmental oxidative stress on airway inflammation. Curr. Opin. Allergy Clin. Immunol. 2012;12:133-139.
Not in our library10.1097/aci.0b013e32835113d6 (opens in a new tab)
11.
Liu C., Zhang Y., Weschler C.J. The impact of mass transfer limitations on size distributions of particle associated SVOCs in outdoor and indoor environments. Sci. Total Environ. 2014;497–498:401-411.
Not in our library10.1016/j.scitotenv.2014.07.095 (opens in a new tab)
12.
Lighty J.S., Veranth J.M., Sarofim A.F. Combustion aerosols: factors governing their size and composition and implications to human health. J. Air Waste Manag. Assoc. 2000;50:1565-1622.
Not in our library10.1080/10473289.2000.10464197 (opens in a new tab)
13.
Cassee F.R., Heroux M.E., Gerlofs-Nijland M.E., Kelly F.J. Particulate matter beyond mass: recent health evidence on the role of fractions, chemical constituents and sources of emission. Inhal. Toxicol. 2013;25:802-812.
Not in our library10.3109/08958378.2013.850127 (opens in a new tab)
14.
Schwarze P.E., Ovrevik J., Hetland R.B., Becher R., Cassee F.R., Lag M., Lovik M., Dybing E., Refsnes M. Importance of size and composition of particles for effects on cells in vitro. Inhal. Toxicol. 2007;19(Suppl 1):17-22.
Not in our library10.1080/08958370701490445 (opens in a new tab)
15.
Ghio A.J., Carraway M.S., Madden M.C. Composition of air pollution particles and oxidative stress in cells, tissues, and living systems. J. Toxicol. Environ. Health B Crit. Rev. 2012;15:1-21.
Not in our library10.1080/10937404.2012.632359 (opens in a new tab)
16.
Cui X., Zhou T., Shen Y., Rong Y., Zhang Z., Liu Y., Xiao L., Zhou Y., Li W., Chen W. Different biological effects of PM2.5 from coal combustion, gasoline exhaust and urban ambient air relate to the PAH/metal compositions. Environ. Toxicol. Pharmacol. 2019;69:120-128.
Not in our library10.1016/j.etap.2019.04.006 (opens in a new tab)
17.
O'Driscoll C.A., Owens L.A., Gallo M.E., Hoffmann E.J., Afrazi A., Han M., Fechner J.H., Schauer J.J., Bradfield C.A., Mezrich J.D. Differential effects of diesel exhaust particles on T cell differentiation and autoimmune disease. Part. Fibre Toxicol. 2018;15:35.
Not in our library10.1186/s12989-018-0271-3 (opens in a new tab)
18.
Gerlofs-Nijland M.E., Rummelhard M., Boere A.J., Leseman D.L., Duffin R., Schins R.P., Borm P.J., Sillanpaa M., Salonen R.O., Cassee F.R. Particle induced toxicity in relation to transition metal and polycyclic aromatic hydrocarbon contents. Environ. Sci. Technol. 2009;43:4729-4736.
Not in our library10.1021/es803176k (opens in a new tab)
19.
Donaldson K., Stone V. Current hypotheses on the mechanisms of toxicity of ultrafine particles. Ann. Ist. Super Sanita. 2003;39:405-410.
Not in our library
20.
Potential Role of Ultrafine Particles in Associations between Airborne Particle Mass and Cardiovascular Health · 2005
No notice
21.
Liu C., Chen R., Sera F., Vicedo-Cabrera A.M., Guo Y., Tong S., Coelho M., Saldiva P.H.N., Lavigne E., Matus P., Valdes Ortega N., Osorio Garcia S., Pascal M., Stafoggia M., Scortichini M., Hashizume M., Honda Y., Hurtado-Diaz M., Cruz J., Nunes B., Teixeira J.P., Kim H., Tobias A., Iniguez C., Forsberg B., Astrom C., Ragettli M.S., Guo Y.L., Chen B.Y., Bell M.L., Wright C.Y., Scovronick N., Garland R.M., Milojevic A., Kysely J., Urban A., Orru H., Indermitte E., Jaakkola J.J.K., Ryti N.R.I., Katsouyanni K., Analitis A., Zanobetti A., Schwartz J., Chen J., Wu T., Cohen A., Gasparrini A., Kan H. Ambient particulate air pollution and daily mortality in 652 cities. N. Engl. J. Med. 2019;381:705-715.
Not in our library10.1056/nejmoa1817364 (opens in a new tab)
22.
Ohlwein S., Kappeler R., Kutlar Joss M., Kunzli N., Hoffmann B. Health effects of ultrafine particles: a systematic literature review update of epidemiological evidence. Int. J. Public Health. 2019;64:547-559.
Not in our library10.1007/s00038-019-01202-7 (opens in a new tab)
23.
Miller M.R., Raftis J.B., Langrish J.P., McLean S.G., Samutrtai P., Connell S.P., Wilson S., Vesey A.T., Fokkens P.H.B., Boere A.J.F., Krystek P., Campbell C.J., Hadoke P.W.F., Donaldson K., Cassee F.R., Newby D.E., Duffin R., Mills N.L. Inhaled nanoparticles accumulate at sites of vascular disease. ACS Nano. 2017;11:4542-4552.
Not in our library10.1021/acsnano.6b08551 (opens in a new tab)
24.
Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms · 2016
No notice
25.
Geller M.D., Ntziachristos L., Mamakos A., Samaras Z., Schmitz D.A., Froines J.R., Sioutas C. Physicochemical and redox characteristics of particulate matter (PM) emitted from gasoline and diesel passenger cars. Atmos. Environ. 2006;40:6988-7004.
Not in our library
26.
Munzel T., Gori T., Al-Kindi S., Deanfield J., Lelieveld J., Daiber A., Rajagopalan S. Effects of gaseous and solid constituents of air pollution on endothelial function. Eur. Heart J. 2018;39:3543-3550.
Not in our library10.1093/eurheartj/ehy481 (opens in a new tab)
27.
Dockery D.W., Pope C.A., Xu X., Spengler J.D., Ware J.H., Fay M.E., Ferris B.G., Speizer F.E. An association between air pollution and mortality in six U.S. cities. N. Engl. J. Med. 1993;329:1753-1759.
Not in our library10.1056/nejm199312093292401 (opens in a new tab)
28.
Pope C.A., Ezzati M., Dockery D.W. Fine-particulate air pollution and life expectancy in the United States. N. Engl. J. Med. 2009;360:376-386.
Not in our library10.1056/nejmsa0805646 (opens in a new tab)
29.
Miller K.A., Siscovick D.S., Sheppard L., Shepherd K., Sullivan J.H., Anderson G.L., Kaufman J.D. Long-term exposure to air pollution and incidence of cardiovascular events in women. N. Engl. J. Med. 2007;356:447-458.
Not in our library10.1056/nejmoa054409 (opens in a new tab)
30.
Ambient Air Pollution and Atherosclerosis in Los Angeles · 2004
No notice
31.
Pope C.A., Burnett R.T., Thurston G.D., Thun M.J., Calle E.E., Krewski D., Godleski J.J. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation. 2004;109:71-77.
Not in our library10.1161/01.cir.0000108927.80044.7f (opens in a new tab)
32.
Hoek G., Brunekreef B., Goldbohm S., Fischer P., van den Brandt P.A. Association between mortality and indicators of traffic-related air pollution in The Netherlands: a cohort study. Lancet. 2002;360:1203-1209.
Not in our library10.1016/s0140-6736(02)11280-3 (opens in a new tab)
33.
The temporal pattern of respiratory and heart disease mortality in response to air pollution. · 2003
No notice
34.
Dominici F., McDermott A., Daniels M., Zeger S.L., Samet J.M. Revised analyses of the national morbidity, mortality, and air pollution study: mortality among residents of 90 cities. J. Toxicol. Environ. Health. 2005;68:1071-1092.
Not in our library10.1080/15287390590935932 (opens in a new tab)
35.
Pope C.A., Muhlestein J.B., May H.T., Renlund D.G., Anderson J.L., Horne B.D. Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution. Circulation. 2006;114:2443-2448.
Not in our library10.1161/circulationaha.106.636977 (opens in a new tab)
36.
Peters A., Dockery D.W., Muller J.E., Mittleman M.A. Increased particulate air pollution and the triggering of myocardial infarction. Circulation. 2001;103:2810-2815.
Not in our library10.1161/01.cir.103.23.2810 (opens in a new tab)
37.
Peters A., von Klot S., Mittleman M.A., Meisinger C., Hormann A., Kuch B., Wichmann H.E. Triggering of acute myocardial infarction by different means of transportation. Eur. J. Prev. Cardiol. 2013;20:750-758.
Not in our library10.1177/2047487312446672 (opens in a new tab)
38.
Bhaskaran K., Hajat S., Armstrong B., Haines A., Herrett E., Wilkinson P., Smeeth L. The effects of hourly differences in air pollution on the risk of myocardial infarction: case crossover analysis of the MINAP database. Bmj. 2011;343.
Not in our library10.1136/bmj.d5531 (opens in a new tab)
39.
Vodonos A., Awad Y.A., Schwartz J. The concentration-response between long-term PM2.5 exposure and mortality; A meta-regression approach. Environ. Res. 2018;166:677-689.
Not in our library10.1016/j.envres.2018.06.021 (opens in a new tab)
40.
Papadogeorgou G., Kioumourtzoglou M.A., Braun D., Zanobetti A. Low levels of air pollution and health: effect estimates, methodological challenges, and future directions. Curr. Environ. Health Rep. 2019;6:105-115.
Not in our library10.1007/s40572-019-00235-7 (opens in a new tab)
41.
Pappin A.J., Christidis T., Pinault L.L., Crouse D.L., Brook J.R., Erickson A., Hystad P., Li C., Martin R.V., Meng J., Weichenthal S., van Donkelaar A., Tjepkema M., Brauer M., Burnett R.T. Examining the shape of the association between low levels of fine particulate matter and mortality across three cycles of the Canadian census health and environment cohort. Environ. Health Perspect. 2019;127.
Not in our library10.1289/ehp5204 (opens in a new tab)
42.
Beelen R., Raaschou-Nielsen O., Stafoggia M., Andersen Z.J., Weinmayr G., Hoffmann B., Wolf K., Samoli E., Fischer P., Nieuwenhuijsen M., Vineis P., Xun W.W., Katsouyanni K., Dimakopoulou K., Oudin A., Forsberg B., Modig L., Havulinna A.S., Lanki T., Turunen A., Oftedal B., Nystad W., Nafstad P., De Faire U., Pedersen N.L., Ostenson C.G., Fratiglioni L., Penell J., Korek M., Pershagen G., Eriksen K.T., Overvad K., Ellermann T., Eeftens M., Peeters P.H., Meliefste K., Wang M., Bueno-de-Mesquita B., Sugiri D., Kramer U., Heinrich J., de Hoogh K., Key T., Peters A., Hampel R., Concin H., Nagel G., Ineichen A., Schaffner E., Probst-Hensch N., Kunzli N., Schindler C., Schikowski T., Adam M., Phuleria H., Vilier A., Clavel-Chapelon F., Declercq C., Grioni S., Krogh V., Tsai M.Y., Ricceri F., Sacerdote C., Galassi C., Migliore E., Ranzi A., Cesaroni G., Badaloni C., Forastiere F., Tamayo I., Amiano P., Dorronsoro M., Katsoulis M., Trichopoulou A., Brunekreef B., Hoek G. Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project. Lancet. 2014;383:785-795.
Not in our library10.1016/s0140-6736(13)62158-3 (opens in a new tab)
43.
Wan G., Rajagopalan S., Sun Q., Zhang K. Real-world exposure of airborne particulate matter triggers oxidative stress in an animal model. Int. J. Physiol. Pathophysiol. Pharmacol. 2010;2:64-68.
Not in our library
44.
Chen H., Goldberg M.S., Burnett R.T., Jerrett M., Wheeler A.J., Villeneuve P.J. Long-term exposure to traffic-related air pollution and cardiovascular mortality. Epidemiology. 2013;24:35-43.
Not in our library10.1097/ede.0b013e318276c005 (opens in a new tab)
45.
Cesaroni G., Forastiere F., Stafoggia M., Andersen Z.J., Badaloni C., Beelen R., Caracciolo B., de Faire U., Erbel R., Eriksen K.T., Fratiglioni L., Galassi C., Hampel R., Heier M., Hennig F., Hilding A., Hoffmann B., Houthuijs D., Jockel K.H., Korek M., Lanki T., Leander K., Magnusson P.K., Migliore E., Ostenson C.G., Overvad K., Pedersen N.L., J J.P., Penell J., Pershagen G., Pyko A., Raaschou-Nielsen O., Ranzi A., Ricceri F., Sacerdote C., Salomaa V., Swart W., Turunen A.W., Vineis P., Weinmayr G., Wolf K., de Hoogh K., Hoek G., Brunekreef B., Peters A. Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project. Bmj. 2014;348:f7412.
Not in our library10.1136/bmj.f7412 (opens in a new tab)
46.
Raza A., Bellander T., Bero-Bedada G., Dahlquist M., Hollenberg J., Jonsson M., Lind T., Rosenqvist M., Svensson L., Ljungman P.L. Short-term effects of air pollution on out-of-hospital cardiac arrest in Stockholm. Eur. Heart J. 2014;35:861-868.
Not in our library10.1093/eurheartj/eht489 (opens in a new tab)
47.
Watkins A., Danilewitz M., Kusha M., Masse S., Urch B., Quadros K., Spears D., Farid T., Nanthakumar K. Air pollution and arrhythmic risk: the smog is yet to clear. Can. J. Cardiol. 2013;29:734-741.
Not in our library10.1016/j.cjca.2012.09.005 (opens in a new tab)
48.
Exposure to ambient air pollution and the incidence of congestive heart failure and acute myocardial infarction: A population-based study of 5.1 million Canadian adults living in Ontario · 2019
Not checked
49.
Malik A.O., Jones P.G., Chan P.S., Peri-Okonny P.A., Hejjaji V., Spertus J.A. Association of long-term exposure to particulate matter and ozone with health status and mortality in patients after myocardial infarction. Circ. Cardiovasc. Qual. Outcomes. 2019;12.
Not in our library10.1161/circoutcomes.119.005598 (opens in a new tab)
50.
Hoek G., Brunekreef B., Fischer P., van Wijnen J. The association between air pollution and heart failure, arrhythmia, embolism, thrombosis, and other cardiovascular causes of death in a time series study. Epidemiology. 2001;12:355-357.
Not in our library10.1097/00001648-200105000-00017 (opens in a new tab)
51.
Atkinson R.W., Carey I.M., Kent A.J., van Staa T.P., Anderson H.R., Cook D.G. Long-term exposure to outdoor air pollution and incidence of cardiovascular diseases. Epidemiology. 2013;24:44-53.
Not in our library10.1097/ede.0b013e318276ccb8 (opens in a new tab)
52.
Shah A.S., Langrish J.P., Nair H., McAllister D.A., Hunter A.L., Donaldson K., Newby D.E., Mills N.L. Global association of air pollution and heart failure: a systematic review and meta-analysis. Lancet. 2013;382:1039-1048.
Not in our library10.1016/s0140-6736(13)60898-3 (opens in a new tab)
53.
Low R.B., Bielory L., Qureshi A.I., Dunn V., Stuhlmiller D.F., Dickey D.A. The relation of stroke admissions to recent weather, airborne allergens, air pollution, seasons, upper respiratory infections, and asthma incidence, September 11, 2001, and day of the week. Stroke. 2006;37:951-957.
Not in our library10.1161/01.str.0000214681.94680.66 (opens in a new tab)
54.
Shah A.S., Lee K.K., McAllister D.A., Hunter A., Nair H., Whiteley W., Langrish J.P., Newby D.E., Mills N.L. Short term exposure to air pollution and stroke: systematic review and meta-analysis. Bmj. 2015;350.
Not in our library10.1136/bmj.h1295 (opens in a new tab)
55.
Long-Term Exposure to Ambient Air Pollution and Incidence of Cerebrovascular Events: Results from 11 European Cohorts within the ESCAPE Project · 2014
No notice
56.
Miller M.R., Shah A.S.V., Bondy S.C., Campbell A. Ambient particles and cerebrovascular disease. Inflammation, Aging and Oxidative Stress. 2016;133-160.
Not in our library
57.
Lee K.K., Miller M.R., Shah A.S.V. Air pollution and stroke. J. Stroke. 2018;20:2-11.
Not in our library10.5853/jos.2017.02894 (opens in a new tab)
58.
Hoffmann B., Moebus S., Kroger K., Stang A., Mohlenkamp S., Dragano N., Schmermund A., Memmesheimer M., Erbel R., Jockel K.H. Residential exposure to urban air pollution, ankle-brachial index, and peripheral arterial disease. Epidemiology. 2009;20:280-288.
Not in our library10.1097/ede.0b013e3181961ac2 (opens in a new tab)
59.
Peng R.D., Chang H.H., Bell M.L., McDermott A., Zeger S.L., Samet J.M., Dominici F. Coarse particulate matter air pollution and hospital admissions for cardiovascular and respiratory diseases among Medicare patients. J. Am. Med. Assoc. 2008;299:2172-2179.
Not in our library10.1001/jama.299.18.2172 (opens in a new tab)
60.
Baccarelli A., Martinelli I., Pegoraro V., Melly S., Grillo P., Zanobetti A., Hou L., Bertazzi P.A., Mannucci P.M., Schwartz J. Living near major traffic roads and risk of deep vein thrombosis. Circulation. 2009;119:3118-3124.
Not in our library10.1161/circulationaha.108.836163 (opens in a new tab)
61.
Franchini M., Guida A., Tufano A., Coppola A. Air pollution, vascular disease and thrombosis: linking clinical data and pathogenic mechanisms. J. Thromb. Haemost. 2012;10:2438-2451.
Not in our library10.1111/jth.12006 (opens in a new tab)
62.
COMEAP. Effects of long-term exposure to ambient air pollution on cardiovascular morbidity: mechanistic evidence. 2018.
Not in our library
63.
Brook R.D., Franklin B., Cascio W., Hong Y., Howard G., Lipsett M., Luepker R., Mittleman M., Samet J., Smith S.C., Tager P I. Expert panel on, A. Prevention science of the American heart, air pollution and cardiovascular disease: a statement for healthcare professionals from the expert panel on population and prevention science of the American heart association. Circulation. 2004;109:2655-2671.
Not in our library10.1161/01.cir.0000128587.30041.c8 (opens in a new tab)
64.
Newby D.E., Mannucci P.M., Tell G.S., Baccarelli A.A., Brook R.D., Donaldson K., Forastiere F., Franchini M., Franco O.H., Graham I., Hoek G., Hoffmann B., Hoylaerts M.F., Kunzli N., Mills N., Pekkanen J., Peters A., Piepoli M.F., Rajagopalan S., Storey R.F., Esc Working Group on Thrombosis E.A.f.C.P., Rehabilitation, Association E.S.C.H.F. Expert position paper on air pollution and cardiovascular disease. Eur. Heart J. 2015;36:83-93b.
Not in our library10.1093/eurheartj/ehu458 (opens in a new tab)
65.
Wilson S.J., Miller M.R., Newby D.E. Effects of diesel exhaust on cardiovascular function and oxidative stress. Antioxidants Redox Signal. 2018;28:819-836.
Not in our library10.1089/ars.2017.7174 (opens in a new tab)
66.
Kelly F.J., Fussell J.C. Linking ambient particulate matter pollution effects with oxidative biology and immune responses. Ann. N. Y. Acad. Sci. 2015;1340:84-94.
Not in our library10.1111/nyas.12720 (opens in a new tab)
67.
Moller P., Jacobsen N.R., Folkmann J.K., Danielsen P.H., Mikkelsen L., Hemmingsen J.G., Vesterdal L.K., Forchhammer L., Wallin H., Loft S. Role of oxidative damage in toxicity of particulates. Free Radic. Res. 2010;44:1-46.
Not in our library10.3109/10715760903300691 (opens in a new tab)
68.
PM2.5, oxidant defence and cardiorespiratory health: a review · 2013
No notice
69.
O'Neill M.S., Veves A., Zanobetti A., Sarnat J.A., Gold D.R., Economides P.A., Horton E.S., Schwartz J. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation. 2005;111:2913-2920.
Not in our library10.1161/circulationaha.104.517110 (opens in a new tab)
70.
Liu L., Ruddy T., Dalipaj M., Poon R., Szyszkowicz M., You H., Dales R.E., Wheeler A.J. Effects of indoor, outdoor, and personal exposure to particulate air pollution on cardiovascular physiology and systemic mediators in seniors. J. Occup. Environ. Med. 2009;51:1088-1098.
Not in our library10.1097/jom.0b013e3181b35144 (opens in a new tab)
71.
Wilker E.H., Ljungman P.L., Rice M.B., Kloog I., Schwartz J., Gold D.R., Koutrakis P., Vita J.A., Mitchell G.F., Vasan R.S., Benjamin E.J., Hamburg N.M., Mittleman M.A. Relation of long-term exposure to air pollution to brachial artery flow-mediated dilation and reactive hyperemia. Am. J. Cardiol. 2014;113:2057-2063.
Not in our library10.1016/j.amjcard.2014.03.048 (opens in a new tab)
72.
Brook R.D., Rajagopalan S. Particulate matter, air pollution, and blood pressure. J. Am. Soc. Hypertens. 2009;3:332-350.
Not in our library10.1016/j.jash.2009.08.005 (opens in a new tab)
73.
Liang R., Zhang B., Zhao X., Ruan Y., Lian H., Fan Z. Effect of exposure to PM2.5 on blood pressure: a systematic review and meta-analysis. J. Hypertens. 2014;32:2130-2140.
Not in our library10.1097/hjh.0000000000000342 (opens in a new tab)
74.
Yang B.Y., Qian Z., Howard S.W., Vaughn M.G., Fan S.J., Liu K.K., Dong G.H. Global association between ambient air pollution and blood pressure: a systematic review and meta-analysis. Environ. Pollut. 2018;235:576-588.
Not in our library10.1016/j.envpol.2018.01.001 (opens in a new tab)
75.
Munzel T., Sorensen M., Gori T., Schmidt F.P., Rao X., Brook J., Chen L.C., Brook R.D., Rajagopalan S. Environmental stressors and cardio-metabolic disease: part I-epidemiologic evidence supporting a role for noise and air pollution and effects of mitigation strategies. Eur. Heart J. 2017;38:550-556.
Not in our library10.1093/eurheartj/ehw269 (opens in a new tab)
76.
Zanobetti A., Canner M.J., Stone P.H., Schwartz J., Sher D., Eagan-Bengston E., Gates K.A., Hartley L.H., Suh H., Gold D.R. Ambient pollution and blood pressure in cardiac rehabilitation patients. Circulation. 2004;110:2184-2189.
Not in our library10.1161/01.cir.0000143831.33243.d8 (opens in a new tab)
77.
Giorgini P., Di Giosia P., Grassi D., Rubenfire M., Brook R.D., Ferri C. Air pollution exposure and blood pressure: an updated review of the literature. Curr. Pharmaceut. Des. 2016;22:28-51.
Not in our library10.2174/1381612822666151109111712 (opens in a new tab)
78.
Schneider A., Neas L., Herbst M.C., Case M., Williams R.W., Cascio W., Hinderliter A., Holguin F., Buse J.B., Dungan K., Styner M., Peters A., Devlin R.B. Endothelial dysfunction: associations with exposure to ambient fine particles in diabetic individuals. Environ. Health Perspect. 2008;116:1666-1674.
Not in our library10.1289/ehp.11666 (opens in a new tab)
79.
Pettit A.P., Kipen H., Laumbach R., Ohman-Strickland P., Kelly-McNeill K., Cepeda C., Fan Z.H., Amorosa L., Lubitz S., Schneider S., Gow A. Disrupted nitric oxide metabolism from type II diabetes and acute exposure to particulate air pollution. PLoS One. 2015;10.
Not in our library10.1371/journal.pone.0144250 (opens in a new tab)
80.
Chuang K.J., Chan C.C., Su T.C., Lee C.T., Tang C.S. The effect of urban air pollution on inflammation, oxidative stress, coagulation, and autonomic dysfunction in young adults. Am. J. Respir. Crit. Care Med. 2007;176:370-376.
Not in our library10.1164/rccm.200611-1627oc (opens in a new tab)
81.
Shigenaga M.K., Ames B.N. Assays for 8-hydroxy-2'-deoxyguanosine: a biomarker of in vivo oxidative DNA damage. Free Radic. Biol. Med. 1991;10:211-216.
Not in our library10.1016/0891-5849(91)90078-h (opens in a new tab)
82.
Ren C., Fang S., Wright R.O., Suh H., Schwartz J. Urinary 8-hydroxy-2'-deoxyguanosine as a biomarker of oxidative DNA damage induced by ambient pollution in the Normative Aging Study. Occup. Environ. Med. 2011;68:562-569.
Not in our library10.1136/oem.2010.056358 (opens in a new tab)
83.
Bagryantseva Y., Novotna B., Rossner P., Chvatalova I., Milcova A., Svecova V., Lnenickova Z., Solansky I., Sram R.J. Oxidative damage to biological macromolecules in Prague bus drivers and garagemen: impact of air pollution and genetic polymorphisms. Toxicol. Lett. 2010;199:60-68.
Not in our library10.1016/j.toxlet.2010.08.007 (opens in a new tab)
84.
Rossner P., Rossnerova A., Sram R.J. Oxidative stress and chromosomal aberrations in an environmentally exposed population. Mutat. Res. 2011;707:34-41.
Not in our library10.1016/j.mrfmmm.2010.12.005 (opens in a new tab)
85.
Personal PM2.5 exposure and markers of oxidative stress in blood. · 2003
No notice
86.
Circulating Biomarkers of Inflammation, Antioxidant Activity, and Platelet Activation Are Associated with Primary Combustion Aerosols in Subjects with Coronary Artery Disease · 2008
No notice
87.
Air Pollution Exposures and Circulating Biomarkers of Effect in a Susceptible Population: Clues to Potential Causal Component mixtures and mechanisms · 2009
No notice
88.
Baccarelli A., Zanobetti A., Martinelli I., Grillo P., Hou L., Lanzani G., Mannucci P.M., Bertazzi P.A., Schwartz J. Air pollution, smoking, and plasma homocysteine. Environ. Health Perspect. 2007;115:176-181.
Not in our library10.1289/ehp.9517 (opens in a new tab)
89.
Baccarelli A., Wright R.O., Bollati V., Tarantini L., Litonjua A.A., Suh H.H., Zanobetti A., Sparrow D., Vokonas P.S., Schwartz J. Rapid DNA methylation changes after exposure to traffic particles. Am. J. Respir. Crit. Care Med. 2009;179:572-578.
Not in our library10.1164/rccm.200807-1097oc (opens in a new tab)
90.
Park S.K., O'Neill M.S., Vokonas P.S., Sparrow D., Spiro A., Tucker K.L., Suh H., Hu H., Schwartz J. Traffic-related particles are associated with elevated homocysteine: the VA normative aging study. Am. J. Respir. Crit. Care Med. 2008;178:283-289.
Not in our library10.1164/rccm.200708-1286oc (opens in a new tab)
91.
Oxidative Damage to DNA and Lipids as Biomarkers of Exposure to Air Pollution · 2010
No notice
92.
Ren C., Park S.K., Vokonas P.S., Sparrow D., Wilker E., Baccarelli A., Suh H.H., Tucker K.L., Wright R.O., Schwartz J. Air pollution and homocysteine: more evidence that oxidative stress-related genes modify effects of particulate air pollution. Epidemiology. 2010;21:198-206.
Not in our library10.1097/ede.0b013e3181cc8bfc (opens in a new tab)
93.
Personal Exposure to Ultrafine Particles and Oxidative DNA Damage · 2005
No notice
94.
Zhang X., Staimer N., Tjoa T., Gillen D.L., Schauer J.J., Shafer M.M., Hasheminassab S., Pakbin P., Longhurst J., Sioutas C., Delfino R.J. Associations between microvascular function and short-term exposure to traffic-related air pollution and particulate matter oxidative potential. Environ. Health. 2016;15:81.
Not in our library10.1186/s12940-016-0157-5 (opens in a new tab)
95.
Kim K.N., Kim J.H., Jung K., Hong Y.C. Associations of air pollution exposure with blood pressure and heart rate variability are modified by oxidative stress genes: a repeated-measures panel among elderly urban residents. Environ. Health. 2016;15:47.
Not in our library10.1186/s12940-016-0130-3 (opens in a new tab)
96.
Wang M., Utell M.J., Schneider A., Zareba W., Frampton M.W., Oakes D., Hopke P.K., Wiltshire J., Kane C., Peters A., Breitner S., Chalupa D., Rich D.Q. Does total antioxidant capacity modify adverse cardiac responses associated with ambient ultrafine, accumulation mode, and fine particles in patients undergoing cardiac rehabilitation? Environ. Res. 2016;149:15-22.
Not in our library10.1016/j.envres.2016.04.031 (opens in a new tab)
97.
Brauner E.V., Forchhammer L., Moller P., Barregard L., Gunnarsen L., Afshari A., Wahlin P., Glasius M., Dragsted L.O., Basu S., Raaschou-Nielsen O., Loft S. Indoor particles affect vascular function in the aged: an air filtration-based intervention study. Am. J. Respir. Crit. Care Med. 2008;177:419-425.
Not in our library10.1164/rccm.200704-632oc (opens in a new tab)
98.
Mordukhovich I., Wilker E., Suh H., Wright R., Sparrow D., Vokonas P.S., Schwartz J. Black carbon exposure, oxidative stress genes, and blood pressure in a repeated-measures study. Environ. Health Perspect. 2009;117:1767-1772.
Not in our library10.1289/ehp.0900591 (opens in a new tab)
99.
Rao X., Patel P., Puett R., Rajagopalan S. Air pollution as a risk factor for type 2 diabetes. Toxicol. Sci. 2015;143:231-241.
Not in our library10.1093/toxsci/kfu250 (opens in a new tab)
100.
Yang B.Y., Fan S., Thiering E., Seissler J., Nowak D., Dong G.H., Heinrich J. Ambient air pollution and diabetes: a systematic review and meta-analysis. Environ. Res. 2019;180.
Not in our library10.1016/j.envres.2019.108817 (opens in a new tab)
101.
Kelishadi R., Mirghaffari N., Poursafa P., Gidding S.S. Lifestyle and environmental factors associated with inflammation, oxidative stress and insulin resistance in children. Atherosclerosis. 2009;203:311-319.
Not in our library10.1016/j.atherosclerosis.2008.06.022 (opens in a new tab)
102.
Jantzen K., Moller P., Karottki D.G., Olsen Y., Beko G., Clausen G., Hersoug L.G., Loft S. Exposure to ultrafine particles, intracellular production of reactive oxygen species in leukocytes and altered levels of endothelial progenitor cells. Toxicology. 2016;359–360:11-18.
Not in our library10.1016/j.tox.2016.06.007 (opens in a new tab)
103.
Behndig A.F., Mudway I.S., Brown J.L., Stenfors N., Helleday R., Duggan S.T., Wilson S.J., Boman C., Cassee F.R., Frew A.J., Kelly F.J., Sandstrom T., Blomberg A. Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans. Eur. Respir. J. 2006;27:359-365.
Not in our library10.1183/09031936.06.00136904 (opens in a new tab)
104.
Mudway I.S., Stenfors N., Duggan S.T., Roxborough H., Zielinski H., Marklund S.L., Blomberg A., Frew A.J., Sandstrom T., Kelly F.J. An in vitro and in vivo investigation of the effects of diesel exhaust on human airway lining fluid antioxidants. Arch. Biochem. Biophys. 2004;423:200-212.
Not in our library10.1016/j.abb.2003.12.018 (opens in a new tab)
105.
Brook R.D., Brook J.R., Urch B., Vincent R., Rajagopalan S., Silverman F. Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circulation. 2002;105:1534-1536.
Not in our library10.1161/01.cir.0000013838.94747.64 (opens in a new tab)
106.
Exposure to Ultrafine Particles from Ambient Air and Oxidative Stress–Induced DNA Damage · 2007
No notice
107.
Mills N.L., Tornqvist H., Robinson S.D., Gonzalez M., Darnley K., MacNee W., Boon N.A., Donaldson K., Blomberg A., Sandstrom T., Newby D.E. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005;112:3930-3936.
Not in our library10.1161/circulationaha.105.588962 (opens in a new tab)
108.
Tornqvist H., Mills N.L., Gonzalez M., Miller M.R., Robinson S.D., Megson I.L., Macnee W., Donaldson K., Soderberg S., Newby D.E., Sandstrom T., Blomberg A. Persistent endothelial dysfunction in humans after diesel exhaust inhalation. Am. J. Respir. Crit. Care Med. 2007;176:395-400.
Not in our library10.1164/rccm.200606-872oc (opens in a new tab)
109.
Barath S., Mills N.L., Lundback M., Tornqvist H., Lucking A.J., Langrish J.P., Soderberg S., Boman C., Westerholm R., Londahl J., Donaldson K., Mudway I.S., Sandstrom T., Newby D.E., Blomberg A. Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions, Part. Fibre Toxicol. 2010;7:19.
Not in our library10.1186/1743-8977-7-19 (opens in a new tab)
110.
Mills N.L., Miller M.R., Lucking A.J., Beveridge J., Flint L., Boere A.J., Fokkens P.H., Boon N.A., Sandstrom T., Blomberg A., Duffin R., Donaldson K., Hadoke P.W., Cassee F.R., Newby D.E. Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation. Eur. Heart J. 2011;32:2660-2671.
Not in our library10.1093/eurheartj/ehr195 (opens in a new tab)
111.
Peretz A., Peck E.C., Bammler T.K., Beyer R.P., Sullivan J.H., Trenga C.A., Srinouanprachnah S., Farin F.M., Kaufman J.D. Diesel exhaust inhalation and assessment of peripheral blood mononuclear cell gene transcription effects: an exploratory study of healthy human volunteers. Inhal. Toxicol. 2007;19:1107-1119.
Not in our library10.1080/08958370701665384 (opens in a new tab)
112.
Langrish J.P., Lundback M., Mills N.L., Johnston N.R., Webb D.J., Sandstrom T., Blomberg A., Newby D.E. Contribution of endothelin 1 to the vascular effects of diesel exhaust inhalation in humans. Hypertension. 2009;54:910-915.
Not in our library10.1161/hypertensionaha.109.135947 (opens in a new tab)
113.
Wauters A., Dreyfuss C., Pochet S., Hendrick P., Berkenboom G., van de Borne P., Argacha J.F. Acute exposure to diesel exhaust impairs nitric oxide-mediated endothelial vasomotor function by increasing endothelial oxidative stress. Hypertension. 2013;62:352-358.
Not in our library10.1161/hypertensionaha.111.00991 (opens in a new tab)
114.
Tong H., Rappold A.G., Caughey M., Hinderliter A.L., Bassett M., Montilla T., Case M.W., Berntsen J., Bromberg P.A., Cascio W.E., Diaz-Sanchez D., Devlin R.B., Samet J.M. Dietary supplementation with olive oil or fish oil and vascular effects of concentrated ambient particulate matter exposure in human volunteers. Environ. Health Perspect. 2015;123:1173-1179.
Not in our library10.1289/ehp.1408988 (opens in a new tab)
115.
Sack C.S., Jansen K.L., Cosselman K.E., Trenga C.A., Stapleton P.L., Allen J., Peretz A., Olives C., Kaufman J.D. Pretreatment with antioxidants augments the acute arterial vasoconstriction caused by diesel exhaust inhalation. Am. J. Respir. Crit. Care Med. 2016;193:1000-1007.
Not in our library10.1164/rccm.201506-1247oc (opens in a new tab)
116.
Lucking A.J., Lundback M., Barath S.L., Mills N.L., Sidhu M.K., Langrish J.P., Boon N.A., Pourazar J., Badimon J.J., Gerlofs-Nijland M.E., Cassee F.R., Boman C., Donaldson K., Sandstrom T., Newby D.E., Blomberg A. Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men. Circulation. 2011;123:1721-1728.
Not in our library10.1161/circulationaha.110.987263 (opens in a new tab)
117.
Langrish J.P., Lundback M., Barath S., Soderberg S., Mills N.L., Newby D.E., Sandstrom T., Blomberg A. Exposure to nitrogen dioxide is not associated with vascular dysfunction in man. Inhal. Toxicol. 2010;22:192-198.
Not in our library10.3109/08958370903144105 (opens in a new tab)
118.
Barath S., Langrish J.P., Lundback M., Bosson J.A., Goudie C., Newby D.E., Sandstrom T., Mills N.L., Blomberg A. Short-term exposure to ozone does not impair vascular function or affect heart rate variability in healthy young men. Toxicol. Sci. 2013;135:292-299.
Not in our library10.1093/toxsci/kft157 (opens in a new tab)
119.
Ozone effects on blood biomarkers of systemic inflammation, oxidative stress, endothelial function, and thrombosis: The Multicenter Ozone Study in oldEr Subjects (MOSES). · 2019
Not checked
120.
Moller P., Mikkelsen L., Vesterdal L.K., Folkmann J.K., Forchhammer L., Roursgaard M., Danielsen P.H., Loft S. Hazard identification of particulate matter on vasomotor dysfunction and progression of atherosclerosis. Crit. Rev. Toxicol. 2011;41:339-368.
Not in our library10.3109/10408444.2010.533152 (opens in a new tab)
121.
Cherng T.W., Paffett M.L., Jackson-Weaver O., Campen M.J., Walker B.R., Kanagy N.L. Mechanisms of diesel-induced endothelial nitric oxide synthase dysfunction in coronary arterioles. Environ. Health Perspect. 2011;119:98-103.
Not in our library10.1289/ehp.1002286 (opens in a new tab)
122.
Davel A.P., Lemos M., Pastro L.M., Pedro S.C., de Andre P.A., Hebeda C., Farsky S.H., Saldiva P.H., Rossoni L.V. Endothelial dysfunction in the pulmonary artery induced by concentrated fine particulate matter exposure is associated with local but not systemic inflammation. Toxicology. 2012;295:39-46.
Not in our library10.1016/j.tox.2012.02.004 (opens in a new tab)
123.
Sun Q., Yue P., Ying Z., Cardounel A.J., Brook R.D., Devlin R., Hwang J.S., Zweier J.L., Chen L.C., Rajagopalan S. Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK. Arterioscler. Thromb. Vasc. Biol. 2008;28:1760-1766.
Not in our library10.1161/atvbaha.108.166967 (opens in a new tab)
124.
Ying Z., Kampfrath T., Thurston G., Farrar B., Lippmann M., Wang A., Sun Q., Chen L.C., Rajagopalan S. Ambient particulates alter vascular function through induction of reactive oxygen and nitrogen species. Toxicol. Sci. 2009;111:80-88.
Not in our library10.1093/toxsci/kfp004 (opens in a new tab)
125.
Xu X., Yavar Z., Verdin M., Ying Z., Mihai G., Kampfrath T., Wang A., Zhong M., Lippmann M., Chen L.C., Rajagopalan S., Sun Q. Effect of early particulate air pollution exposure on obesity in mice: role of p47phox. Arterioscler. Thromb. Vasc. Biol. 2010;30:2518-2527.
Not in our library10.1161/atvbaha.110.215350 (opens in a new tab)
126.
Labranche N., El Khattabi C., Dewachter L., Dreyfuss C., Fontaine J., van de Borne P., Berkenboom G., Pochet S. Vascular oxidative stress induced by diesel exhaust microparticles: synergism with hypertension. J. Cardiovasc. Pharmacol. 2012;60:530-537.
Not in our library10.1097/fjc.0b013e318270f1a8 (opens in a new tab)
127.
Kampfrath T., Maiseyeu A., Ying Z., Shah Z., Deiuliis J.A., Xu X., Kherada N., Brook R.D., Reddy K.M., Padture N.P., Parthasarathy S., Chen L.C., Moffatt-Bruce S., Sun Q., Morawietz H., Rajagopalan S. Chronic fine particulate matter exposure induces systemic vascular dysfunction via NADPH oxidase and TLR4 pathways. Circ. Res. 2011;108:716-726.
Not in our library10.1161/circresaha.110.237560 (opens in a new tab)
128.
Systemic Microvascular Dysfunction and Inflammation after Pulmonary Particulate Matter Exposure · 2005
No notice
129.
Cui Y., Sun Q., Liu Z. Ambient particulate matter exposure and cardiovascular diseases: a focus on progenitor and stem cells. J. Cell Mol. Med. 2016;20:782-793.
Not in our library10.1111/jcmm.12822 (opens in a new tab)
130.
Haberzettl P., McCracken J.P., Bhatnagar A., Conklin D.J. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis. Am. J. Physiol. Heart Circ. Physiol. 2016;310:H1423-H1438.
Not in our library10.1152/ajpheart.00369.2015 (opens in a new tab)
131.
Haberzettl P., Conklin D.J., Abplanalp W.T., Bhatnagar A., O'Toole T.E. Inhalation of fine particulate matter impairs endothelial progenitor cell function via pulmonary oxidative stress. Arterioscler. Thromb. Vasc. Biol. 2018;38:131-142.
Not in our library10.1161/atvbaha.117.309971 (opens in a new tab)
132.
Miller M.R., Borthwick S.J., Shaw C.A., McLean S.G., McClure D., Mills N.L., Duffin R., Donaldson K., Megson I.L., Hadoke P.W., Newby D.E. Direct impairment of vascular function by diesel exhaust particulate through reduced bioavailability of endothelium-derived nitric oxide induced by superoxide free radicals. Environ. Health Perspect. 2009;117:611-616.
Not in our library10.1289/ehp.0800235 (opens in a new tab)
133.
Shaw C.A., Robertson S., Miller M.R., Duffin R., Tabor C.M., Donaldson K., Newby D.E., Hadoke P.W. Diesel exhaust particulate--exposed macrophages cause marked endothelial cell activation. Am. J. Respir. Cell Mol. Biol. 2011;44:840-851.
Not in our library10.1165/rcmb.2010-0011oc (opens in a new tab)
134.
Hartz A.M., Bauer B., Block M.L., Hong J.S., Miller D.S. Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier. FASEB J. 2008;22:2723-2733.
Not in our library10.1096/fj.08-106997 (opens in a new tab)
135.
Du Y., Navab M., Shen M., Hill J., Pakbin P., Sioutas C., Hsiai T.K., Li R. Ambient ultrafine particles reduce endothelial nitric oxide production via S-glutathionylation of eNOS. Biochem. Biophys. Res. Commun. 2013;436:462-466.
Not in our library10.1016/j.bbrc.2013.05.127 (opens in a new tab)
136.
Rui W., Guan L., Zhang F., Zhang W., Ding W. PM2.5-induced oxidative stress increases adhesion molecules expression in human endothelial cells through the ERK/AKT/NF-kappaB-dependent pathway. J. Appl. Toxicol. 2016;36:48-59.
Not in our library10.1002/jat.3143 (opens in a new tab)
137.
Mo Y., Wan R., Chien S., Tollerud D.J., Zhang Q. Activation of endothelial cells after exposure to ambient ultrafine particles: the role of NADPH oxidase. Toxicol. Appl. Pharmacol. 2009;236:183-193.
Not in our library10.1016/j.taap.2009.01.017 (opens in a new tab)
138.
Li R., Ning Z., Cui J., Khalsa B., Ai L., Takabe W., Beebe T., Majumdar R., Sioutas C., Hsiai T. Ultrafine particles from diesel engines induce vascular oxidative stress via JNK activation. Free Radic. Biol. Med. 2009;46:775-782.
Not in our library10.1016/j.freeradbiomed.2008.11.025 (opens in a new tab)
139.
Tseng C.Y., Wang J.S., Chang Y.J., Chang J.F., Chao M.W. Exposure to high-dose diesel exhaust particles induces intracellular oxidative stress and causes endothelial apoptosis in cultured in vitro capillary tube cells. Cardiovasc. Toxicol. 2015;15:345-354.
Not in our library10.1007/s12012-014-9302-y (opens in a new tab)
140.
Lee C.C., Huang S.H., Yang Y.T., Cheng Y.W., Li C.H., Kang J.J. Motorcycle exhaust particles up-regulate expression of vascular adhesion molecule-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, Toxicol. In Vitro. 2012;26:552-560.
Not in our library10.1016/j.tiv.2012.01.021 (opens in a new tab)
141.
Sharma K., Lee H.H., Gong D.S., Park S.H., Yi E., Schini-Kerth V., Oak M.H. Fine air pollution particles induce endothelial senescence via redox-sensitive activation of local angiotensin system. Environ. Pollut. 2019;252(Pt A):317-329.
Not in our library10.1016/j.envpol.2019.05.066 (opens in a new tab)
142.
Tseng C.Y., Chang J.F., Wang J.S., Chang Y.J., Gordon M.K., Chao M.W. Protective effects of N-acetyl cysteine against diesel exhaust particles-induced intracellular ROS generates pro-inflammatory cytokines to mediate the vascular permeability of capillary-like endothelial tubes. PLoS One. 2015;10.
Not in our library10.1371/journal.pone.0131911 (opens in a new tab)
143.
Hoffmann B., Moebus S., Mohlenkamp S., Stang A., Lehmann N., Dragano N., Schmermund A., Memmesheimer M., Mann K., Erbel R., Jockel K.H. Residential exposure to traffic is associated with coronary atherosclerosis. Circulation. 2007;116:489-496.
Not in our library10.1161/circulationaha.107.693622 (opens in a new tab)
144.
Provost E.B., Madhloum N., Int Panis L., De Boever P., Nawrot T.S. Carotid intima-media thickness, a marker of subclinical atherosclerosis, and particulate air pollution exposure: the meta-analytical evidence. PLoS One. 2015;10.
Not in our library10.1371/journal.pone.0127014 (opens in a new tab)
145.
Adar S.D., Klein R., Klein B.E., Szpiro A.A., Cotch M.F., Wong T.Y., O'Neill M.S., Shrager S., Barr R.G., Siscovick D.S., Daviglus M.L., Sampson P.D., Kaufman J.D. Air Pollution and the microvasculature: a cross-sectional assessment of in vivo retinal images in the population-based multi-ethnic study of atherosclerosis (MESA). PLoS Med. 2010;7.
Not in our library10.1371/journal.pmed.1000372 (opens in a new tab)
146.
Kunzli N., Perez L., von Klot S., Baldassarre D., Bauer M., Basagana X., Breton C., Dratva J., Elosua R., de Faire U., Fuks K., de Groot E., Marrugat J., Penell J., Seissler J., Peters A., Hoffmann B. Investigating air pollution and atherosclerosis in humans: concepts and outlook. Prog. Cardiovasc. Dis. 2011;53:334-343.
Not in our library10.1016/j.pcad.2010.12.006 (opens in a new tab)
147.
Louwies T., Vuegen C., Panis L.I., Cox B., Vrijens K., Nawrot T.S., De Boever P. miRNA expression profiles and retinal blood vessel calibers are associated with short-term particulate matter air pollution exposure. Environ. Res. 2016;147:24-31.
Not in our library10.1016/j.envres.2016.01.027 (opens in a new tab)
148.
Tonne C., Yanosky J.D., Beevers S., Wilkinson P., Kelly F.J. PM mass concentration and PM oxidative potential in relation to carotid intima-media thickness. Epidemiology. 2012;23:486-494.
Not in our library10.1097/ede.0b013e31824e613e (opens in a new tab)
149.
Rossner P., Svecova V., Milcova A., Lnenickova Z., Solansky I., Santella R.M., Sram R.J. Oxidative and nitrosative stress markers in bus drivers. Mutat. Res. 2007;617:23-32.
Not in our library10.1016/j.mrfmmm.2006.11.033 (opens in a new tab)
150.
Brucker N., Moro A.M., Charao M.F., Durgante J., Freitas F., Baierle M., Nascimento S., Gauer B., Bulcao R.P., Bubols G.B., Ferrari P.D., Thiesen F.V., Gioda A., Duarte M.M., de Castro I., Saldiva P.H., Garcia S.C. Biomarkers of occupational exposure to air pollution, inflammation and oxidative damage in taxi drivers. Sci. Total Environ. 2013;463–464:884-893.
Not in our library10.1016/j.scitotenv.2013.06.098 (opens in a new tab)
151.
Jiang S., Bo L., Gong C., Du X., Kan H., Xie Y., Song W., Zhao J. Traffic-related air pollution is associated with cardio-metabolic biomarkers in general residents. Int. Arch. Occup. Environ. Health. 2016;89:911-921.
Not in our library10.1007/s00420-016-1129-3 (opens in a new tab)
152.
Wu S., Yang D., Wei H., Wang B., Huang J., Li H., Shima M., Deng F., Guo X. Association of chemical constituents and pollution sources of ambient fine particulate air pollution and biomarkers of oxidative stress associated with atherosclerosis: a panel study among young adults in Beijing, China. Chemosphere. 2015;135:347-353.
Not in our library10.1016/j.chemosphere.2015.04.096 (opens in a new tab)
153.
Madrigano J., Baccarelli A., Wright R.O., Suh H., Sparrow D., Vokonas P.S., Schwartz J. Air pollution, obesity, genes and cellular adhesion molecules. Occup. Environ. Med. 2010;67:312-317.
Not in our library10.1136/oem.2009.046193 (opens in a new tab)
154.
Lin Z., Chen R., Jiang Y., Xia Y., Niu Y., Wang C., Liu C., Chen C., Ge Y., Wang W., Yin G., Cai J., Clement V., Xu X., Chen B., Chen H., Kan H. Cardiovascular benefits of fish-oil supplementation against fine particulate air pollution in China. J. Am. Coll. Cardiol. 2019;73:2076-2085.
Not in our library10.1016/j.jacc.2018.12.093 (opens in a new tab)
155.
Rodosthenous R.S., Coull B.A., Lu Q., Vokonas P.S., Schwartz J.D., Baccarelli A.A. Ambient particulate matter and microRNAs in extracellular vesicles: a pilot study of older individuals, Part. Fibre Toxicol. 2016;13:13.
Not in our library10.1186/s12989-016-0121-0 (opens in a new tab)
156.
Lund A.K., Lucero J., Harman M., Madden M.C., McDonald J.D., Seagrave J.C., Campen M.J. The oxidized low-density lipoprotein receptor mediates vascular effects of inhaled vehicle emissions. Am. J. Respir. Crit. Care Med. 2011;184:82-91.
Not in our library10.1164/rccm.201012-1967oc (opens in a new tab)
157.
Ramanathan G., Yin F., Speck M., Tseng C.H., Brook J.R., Silverman F., Urch B., Brook R.D., Araujo J.A. Effects of urban fine particulate matter and ozone on HDL functionality, Part. Fibre Toxicol. 2016;13:26.
Not in our library10.1186/s12989-016-0139-3 (opens in a new tab)
158.
Ikeda M., Shitashige M., Yamasaki H., Sagai M., Tomita T. Oxidative modification of low density lipoprotein by diesel exhaust particles. Biol. Pharm. Bull. 1995;18:866-871.
Not in our library10.1248/bpb.18.866 (opens in a new tab)
159.
Soares S.R., Carvalho-Oliveira R., Ramos-Sanchez E., Catanozi S., da Silva L.F., Mauad T., Gidlund M., Goto H., Garcia M.L. Air pollution and antibodies against modified lipoproteins are associated with atherosclerosis and vascular remodeling in hyperlipemic mice. Atherosclerosis. 2009;207:368-373.
Not in our library10.1016/j.atherosclerosis.2009.04.041 (opens in a new tab)
160.
Gong K.W., Zhao W., Li N., Barajas B., Kleinman M., Sioutas C., Horvath S., Lusis A.J., Nel A., Araujo J.A. Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells. Genome Biol. 2007;8:R149.
Not in our library10.1186/gb-2007-8-7-r149 (opens in a new tab)
161.
Miller M.R., McLean S.G., Duffin R., Lawal A.O., Araujo J.A., Shaw C.A., Mills N.L., Donaldson K., Newby D.E., Hadoke P.W. Diesel exhaust particulate increases the size and complexity of lesions in atherosclerotic mice, Part. Fibre Toxicol. 2013;10:61.
Not in our library10.1186/1743-8977-10-61 (opens in a new tab)
162.
Bai N., Kido T., Kavanagh T.J., Kaufman J.D., Rosenfeld M.E., van Breemen C., van Eeden S.F. Exposure to diesel exhaust up-regulates iNOS expression in ApoE knockout mice. Toxicol. Appl. Pharmacol. 2011;255:184-192.
Not in our library10.1016/j.taap.2011.06.013 (opens in a new tab)
163.
Lund A.K., Knuckles T.L., Obot Akata C., Shohet R., McDonald J.D., Gigliotti A., Seagrave J.C., Campen M.J. Gasoline exhaust emissions induce vascular remodeling pathways involved in atherosclerosis. Toxicol. Sci. 2007;95:485-494.
Not in our library10.1093/toxsci/kfl145 (opens in a new tab)
164.
Araujo J.A., Barajas B., Kleinman M., Wang X., Bennett B.J., Gong K.W., Navab M., Harkema J., Sioutas C., Lusis A.J., Nel A.E. Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress. Circ. Res. 2008;102:589-596.
Not in our library10.1161/circresaha.107.164970 (opens in a new tab)
165.
Sun Q., Wang A., Jin X., Natanzon A., Duquaine D., Brook R.D., Aguinaldo J.G., Fayad Z.A., Fuster V., Lippmann M., Chen L.C., Rajagopalan S. Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. Jama. 2005;294:3003-3010.
Not in our library10.1001/jama.294.23.3003 (opens in a new tab)
166.
Yin F., Lawal A., Ricks J., Fox J.R., Larson T., Navab M., Fogelman A.M., Rosenfeld M.E., Araujo J.A. Diesel exhaust induces systemic lipid peroxidation and development of dysfunctional pro-oxidant and proinflammatory high-density lipoprotein. Arterioscler. Thromb. Vasc. Biol. 2013;33:1153-1161.
Not in our library10.1161/atvbaha.112.300552 (opens in a new tab)
167.
Kodavanti U.P., Thomas R., Ledbetter A.D., Schladweiler M.C., Shannahan J.H., Wallenborn J.G., Lund A.K., Campen M.J., Butler E.O., Gottipolu R.R., Nyska A., Richards J.E., Andrews D., Jaskot R.H., McKee J., Kotha S.R., Patel R.B., Parinandi N.L. Vascular and cardiac impairments in rats inhaling ozone and diesel exhaust particles. Environ. Health Perspect. 2011;119:312-318.
Not in our library10.1289/ehp.1002386 (opens in a new tab)
168.
Li R., Navab M., Pakbin P., Ning Z., Navab K., Hough G., Morgan T.E., Finch C.E., Araujo J.A., Fogelman A.M., Sioutas C., Hsiai T. Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice. J. Lipid Res. 2013;54:1608-1615.
Not in our library10.1194/jlr.m035014 (opens in a new tab)
169.
Lawal A.O. Air particulate matter induced oxidative stress and inflammation in cardiovascular disease and atherosclerosis: the role of Nrf2 and AhR-mediated pathways. Toxicol. Lett. 2017;270:88-95.
Not in our library10.1016/j.toxlet.2017.01.017 (opens in a new tab)
170.
Bai N., Kido T., Suzuki H., Yang G., Kavanagh T.J., Kaufman J.D., Rosenfeld M.E., van Breemen C., Eeden S.F. Changes in atherosclerotic plaques induced by inhalation of diesel exhaust. Atherosclerosis. 2011;216:299-306.
Not in our library10.1016/j.atherosclerosis.2011.02.019 (opens in a new tab)
171.
Aztatzi-Aguilar O.G., Uribe-Ramirez M., Arias-Montano J.A., Barbier O., De Vizcaya-Ruiz A. Acute and subchronic exposure to air particulate matter induces expression of angiotensin and bradykinin-related genes in the lungs and heart: angiotensin-II type-I receptor as a molecular target of particulate matter exposure. Part. Fibre Toxicol. 2015;12:17.
Not in our library10.1186/s12989-015-0094-4 (opens in a new tab)
172.
Quan C., Sun Q., Lippmann M., Chen L.C. Comparative effects of inhaled diesel exhaust and ambient fine particles on inflammation, atherosclerosis, and vascular dysfunction. Inhal. Toxicol. 2010;22:738-753.
Not in our library10.3109/08958371003728057 (opens in a new tab)
173.
Campen M.J., Lund A.K., Knuckles T.L., Conklin D.J., Bishop B., Young D., Seilkop S., Seagrave J., Reed M.D., McDonald J.D. Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE(-/-) mice. Toxicol. Appl. Pharmacol. 2010;242:310-317.
Not in our library10.1016/j.taap.2009.10.021 (opens in a new tab)
174.
Zeng X., Liu J., Du X., Zhang J., Pan K., Shan W., Xie Y., Song W., Zhao J. The protective effects of selenium supplementation on ambient PM2.5-induced cardiovascular injury in rats. Environ. Sci. Pollut. Res. Int. 2018;25:22153-22162.
Not in our library10.1007/s11356-018-2292-8 (opens in a new tab)
175.
Buteau S., Goldberg M.S. A structured review of panel studies used to investigate associations between ambient air pollution and heart rate variability. Environ. Res. 2016;148:207-247.
Not in our library10.1016/j.envres.2016.03.013 (opens in a new tab)
176.
Lee M.S., Eum K.D., Fang S.C., Rodrigues E.G., Modest G.A., Christiani D.C. Oxidative stress and systemic inflammation as modifiers of cardiac autonomic responses to particulate air pollution. Int. J. Cardiol. 2014;176:166-170.
Not in our library10.1016/j.ijcard.2014.07.012 (opens in a new tab)
177.
Schwartz J., Park S.K., O'Neill M.S., Vokonas P.S., Sparrow D., Weiss S., Kelsey K. Glutathione-S-transferase M1, obesity, statins, and autonomic effects of particles: gene-by-drug-by-environment interaction. Am. J. Respir. Crit. Care Med. 2005;172:1529-1533.
Not in our library10.1164/rccm.200412-1698oc (opens in a new tab)
178.
Particulate Air Pollution, Oxidative Stress Genes, and Heart Rate Variability in an Elderly Cohort · 2007
No notice
179.
Park S.K., O'Neill M.S., Wright R.O., Hu H., Vokonas P.S., Sparrow D., Suh H., Schwartz J. HFE genotype, particulate air pollution, and heart rate variability: a gene-environment interaction. Circulation. 2006;114:2798-2805.
Not in our library10.1161/circulationaha.106.643197 (opens in a new tab)
180.
Baja E.S., Schwartz J.D., Wellenius G.A., Coull B.A., Zanobetti A., Vokonas P.S., Suh H.H. Traffic-related air pollution and QT interval: modification by diabetes, obesity, and oxidative stress gene polymorphisms in the normative aging study. Environ. Health Perspect. 2010;118:840-846.
Not in our library10.1289/ehp.0901396 (opens in a new tab)
181.
Baccarelli A., Cassano P.A., Litonjua A., Park S.K., Suh H., Sparrow D., Vokonas P., Schwartz J. Cardiac autonomic dysfunction: effects from particulate air pollution and protection by dietary methyl nutrients and metabolic polymorphisms. Circulation. 2008;117:1802-1809.
Not in our library10.1161/circulationaha.107.726067 (opens in a new tab)
182.
Mordukhovich I., Kloog I., Coull B., Koutrakis P., Vokonas P., Schwartz J. Association between particulate air pollution and QT interval duration in an elderly cohort. Epidemiology. 2016;27:284-290.
Not in our library10.1097/ede.0000000000000424 (opens in a new tab)
183.
Sarnat J.A., Golan R., Greenwald R., Raysoni A.U., Kewada P., Winquist A., Sarnat S.E., Dana Flanders W., Mirabelli M.C., Zora J.E., Bergin M.H., Yip F. Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters. Environ. Res. 2014;133:66-76.
Not in our library10.1016/j.envres.2014.05.004 (opens in a new tab)
184.
Reducing Personal Exposure to Particulate Air Pollution Improves Cardiovascular Health in Patients with Coronary Heart Disease · 2012
No notice
185.
Zhang J., Zhu T., Kipen H., Wang G., Huang W., Rich D., Zhu P., Wang Y., Lu S.E., Ohman-Strickland P., Diehl S., Hu M., Tong J., Gong J., Thomas D., Committee H.E.I.H.R. Cardiorespiratory biomarker responses in healthy young adults to drastic air quality changes surrounding the 2008 Beijing Olympics. Res. Rep. Health Eff. Inst. 2013;174:5-174.
Not in our library
186.
Romieu I., Tellez-Rojo M.M., Lazo M., Manzano-Patino A., Cortez-Lugo M., Julien P., Belanger M.C., Hernandez-Avila M., Holguin F. Omega-3 fatty acid prevents heart rate variability reductions associated with particulate matter. Am. J. Respir. Crit. Care Med. 2005;172:1534-1540.
Not in our library10.1164/rccm.200503-372oc (opens in a new tab)
187.
Tong H., Rappold A.G., Diaz-Sanchez D., Steck S.E., Berntsen J., Cascio W.E., Devlin R.B., Samet J.M. Omega-3 fatty acid supplementation appears to attenuate particulate air pollution-induced cardiac effects and lipid changes in healthy middle-aged adults. Environ. Health Perspect. 2012;120:952-957.
Not in our library10.1289/ehp.1104472 (opens in a new tab)
188.
Devlin R.B., Smith C.B., Schmitt M.T., Rappold A.G., Hinderliter A., Graff D., Carraway M.S. Controlled exposure of humans with metabolic syndrome to concentrated ultrafine ambient particulate matter causes cardiovascular effects. Toxicol. Sci. 2014;140:61-72.
Not in our library10.1093/toxsci/kfu063 (opens in a new tab)
189.
Hemmingsen J.G., Rissler J., Lykkesfeldt J., Sallsten G., Kristiansen J., Moller P.P., Loft S. Controlled exposure to particulate matter from urban street air is associated with decreased vasodilation and heart rate variability in overweight and older adults, Part. Fibre Toxicol. 2015;12:6.
Not in our library10.1186/s12989-015-0081-9 (opens in a new tab)
190.
Perez C.M., Hazari M.S., Farraj A.K. Role of autonomic reflex arcs in cardiovascular responses to air pollution exposure. Cardiovasc. Toxicol. 2015;15:69-78.
Not in our library10.1007/s12012-014-9272-0 (opens in a new tab)
191.
Carll A.P., Haykal-Coates N., Winsett D.W., Hazari M.S., Ledbetter A.D., Richards J.H., Cascio W.E., Costa D.L., Farraj A.K. Cardiomyopathy confers susceptibility to particulate matter-induced oxidative stress, vagal dominance, arrhythmia and pulmonary inflammation in heart failure-prone rats. Inhal. Toxicol. 2015;27:100-112.
Not in our library10.3109/08958378.2014.995387 (opens in a new tab)
192.
Carll A.P., Haykal-Coates N., Winsett D.W., Rowan W.H., Hazari M.S., Ledbetter A.D., Nyska A., Cascio W.E., Watkinson W.P., Costa D.L., Farraj A.K. Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy. Inhal. Toxicol. 2010;22:355-368.
Not in our library10.3109/08958370903365692 (opens in a new tab)
193.
Carll A.P., Lust R.M., Hazari M.S., Perez C.M., Krantz Q.T., King C.J., Winsett D.W., Cascio W.E., Costa D.L., Farraj A.K. Diesel exhaust inhalation increases cardiac output, bradyarrhythmias, and parasympathetic tone in aged heart failure-prone rats. Toxicol. Sci. 2013;131:583-595.
Not in our library10.1093/toxsci/kfs295 (opens in a new tab)
194.
Ghelfi E., Wellenius G.A., Lawrence J., Millet E., Gonzalez-Flecha B. Cardiac oxidative stress and dysfunction by fine concentrated ambient particles (CAPs) are mediated by angiotensin-II. Inhal. Toxicol. 2010;22:963-972.
Not in our library10.3109/08958378.2010.503322 (opens in a new tab)
195.
Rhoden C.R., Wellenius G.A., Ghelfi E., Lawrence J., Gonzalez-Flecha B. PM-induced cardiac oxidative stress and dysfunction are mediated by autonomic stimulation. Biochim. Biophys. Acta. 2005;1725:305-313.
Not in our library10.1016/j.bbagen.2005.05.025 (opens in a new tab)
196.
Robertson S., Thomson A.L., Carter R., Stott H.R., Shaw C.A., Hadoke P.W., Newby D.E., Miller M.R., Gray G.A. Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and beta1 adrenoreceptors, Part. Fibre Toxicol. 2014;11:12.
Not in our library10.1186/1743-8977-11-12 (opens in a new tab)
197.
Wang G., Jiang R., Zhao Z., Song W. Effects of ozone and fine particulate matter (PM(2.5)) on rat system inflammation and cardiac function. Toxicol. Lett. 2013;217:23-33.
Not in our library10.1016/j.toxlet.2012.11.009 (opens in a new tab)
198.
Kim J.B., Kim C., Choi E., Park S., Park H., Pak H.N., Lee M.H., Shin D.C., Hwang K.C., Joung B. Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation. Toxicol. Appl. Pharmacol. 2012;259:66-73.
Not in our library10.1016/j.taap.2011.12.007 (opens in a new tab)
199.
Cascio W.E. Proposed pathophysiologic framework to explain some excess cardiovascular death associated with ambient air particle pollution: insights for public health translation. Biochim. Biophys. Acta. 2016;1860:2869-2879.
Not in our library10.1016/j.bbagen.2016.07.016 (opens in a new tab)
200.
Dominguez-Rodriguez A., Rodriguez S., Abreu-Gonzalez P., Avanzas P., Juarez-Prera R.A. Black carbon exposure, oxidative stress markers and major adverse cardiovascular events in patients with acute coronary syndromes. Int. J. Cardiol. 2015;188:47-49.
Not in our library10.1016/j.ijcard.2015.04.023 (opens in a new tab)
201.
Pekkanen J., Peters A., Hoek G., Tiittanen P., Brunekreef B., de Hartog J., Heinrich J., Ibald-Mulli A., Kreyling W.G., Lanki T., Timonen K.L., Vanninen E. Particulate air pollution and risk of ST-segment depression during repeated submaximal exercise tests among subjects with coronary heart disease: the Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air (ULTRA) study. Circulation. 2002;106:933-938.
Not in our library10.1161/01.cir.0000027561.41736.3c (opens in a new tab)
202.
Ambient PM2.5 and risk of emergency room visits for myocardial infarction: impact of regional PM2.5 oxidative potential: a case-crossover study · 2016
No notice
203.
Interaction effects of long-term air pollution exposure and variants in the GSTP1, GSTT1 and GSTCD genes on risk of acute myocardial infarction and hypertension: a case-control study. · 2014
Not checked
204.
Mills N.L., Tornqvist H., Gonzalez M.C., Vink E., Robinson S.D., Soderberg S., Boon N.A., Donaldson K., Sandstrom T., Blomberg A., Newby D.E. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N. Engl. J. Med. 2007;357:1075-1082.
Not in our library10.1056/nejmoa066314 (opens in a new tab)
205.
Dianat M., Radmanesh E., Badavi M., Mard S.A., Goudarzi G. Disturbance effects of PM(1)(0) on iNOS and eNOS mRNA expression levels and antioxidant activity induced by ischemia-reperfusion injury in isolated rat heart: protective role of vanillic acid. Environ. Sci. Pollut. Res. Int. 2016;23:5154-5165.
Not in our library10.1007/s11356-015-5759-x (opens in a new tab)
206.
Gottipolu R.R., Wallenborn J.G., Karoly E.D., Schladweiler M.C., Ledbetter A.D., Krantz T., Linak W.P., Nyska A., Johnson J.A., Thomas R., Richards J.E., Jaskot R.H., Kodavanti U.P. One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats. Environ. Health Perspect. 2009;117:38-46.
Not in our library10.1289/ehp.11647 (opens in a new tab)
207.
Perepu R.S., Garcia C., Dostal D., Sethi R. Enhanced death signaling in ozone-exposed ischemic-reperfused hearts. Mol. Cell. Biochem. 2010;336:55-64.
Not in our library10.1007/s11010-009-0265-4 (opens in a new tab)
208.
Meyer G., Andre L., Tanguy S., Boissiere J., Farah C., Lopez-Lauri F., Gayrard S., Richard S., Boucher F., Cazorla O., Obert P., Reboul C. Simulated urban carbon monoxide air pollution exacerbates rat heart ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 2010;298:H1445-H1453.
Not in our library10.1152/ajpheart.01194.2009 (opens in a new tab)
209.
Gorr M.W., Youtz D.J., Eichenseer C.M., Smith K.E., Nelin T.D., Cormet-Boyaka E., Wold L.E. In vitro particulate matter exposure causes direct and lung-mediated indirect effects on cardiomyocyte function. Am. J. Physiol. Heart Circ. Physiol. 2015;309:H53-H62.
Not in our library10.1152/ajpheart.00162.2015 (opens in a new tab)
210.
Wold L.E., Ying Z., Hutchinson K.R., Velten M., Gorr M.W., Velten C., Youtz D.J., Wang A., Lucchesi P.A., Sun Q., Rajagopalan S. Cardiovascular remodeling in response to long-term exposure to fine particulate matter air pollution. Circ. Heart Fail. 2012;5:452-461.
Not in our library10.1161/circheartfailure.112.966580 (opens in a new tab)
211.
Knuckles T.L., Jaskot R., Richards J.H., Miller C.A., Ledbetter A., McGee J., Linak W.P., Dreher K.L. Biokinetically-based in vitro cardiotoxicity of residual oil fly ash: hazard identification and mechanisms of injury. Cardiovasc. Toxicol. 2013;13:426-437.
Not in our library10.1007/s12012-013-9225-z (opens in a new tab)
212.
Forman H.J., Augusto O., Brigelius-Flohe R., Dennery P.A., Kalyanaraman B., Ischiropoulos H., Mann G.E., Radi R., Roberts L.J., Vina J., Davies K.J. Even free radicals should follow some rules: a guide to free radical research terminology and methodology. Free Radic. Biol. Med. 2015;78:233-235.
Not in our library10.1016/j.freeradbiomed.2014.10.504 (opens in a new tab)
213.
Van Hee V.C., Adar S.D., Szpiro A.A., Barr R.G., Bluemke D.A., Diez Roux A.V., Gill E.A., Sheppard L., Kaufman J.D. Exposure to traffic and left ventricular mass and function: the Multi-Ethnic Study of Atherosclerosis. Am. J. Respir. Crit. Care Med. 2009;179:827-834.
Not in our library10.1164/rccm.200808-1344oc (opens in a new tab)
214.
Van Hee V.C., Adar S.D., Szpiro A.A., Barr R.G., Diez Roux A., Bluemke D.A., Sheppard L., Gill E.A., Bahrami H., Wassel C., Sale M.M., Siscovick D.S., Rotter J.I., Rich S.S., Kaufman J.D. Common genetic variation, residential proximity to traffic exposure, and left ventricular mass: the multi-ethnic study of atherosclerosis. Environ. Health Perspect. 2010;118:962-969.
Not in our library10.1289/ehp.0901535 (opens in a new tab)
215.
Bates J.T., Weber R.J., Abrams J., Verma V., Fang T., Klein M., Strickland M.J., Sarnat S.E., Chang H.H., Mulholland J.A., Tolbert P.E., Russell A.G. Reactive oxygen species generation linked to sources of atmospheric particulate matter and cardiorespiratory effects. Environ. Sci. Technol. 2015;49:13605-13612.
Not in our library10.1021/acs.est.5b02967 (opens in a new tab)
216.
Forman H.J., Finch C.E. A critical review of assays for hazardous components of air pollution. Free Radic. Biol. Med. 2018;117:202-217.
Not in our library10.1016/j.freeradbiomed.2018.01.030 (opens in a new tab)
217.
The role of air pollution in myocardial remodeling. · 2017
Not checked
218.
Yue W., Tong L., Liu X., Weng X., Chen X., Wang D., Dudley S.C., Weir E.K., Ding W., Lu Z., Xu Y., Chen Y. Short term Pm2.5 exposure caused a robust lung inflammation, vascular remodeling, and exacerbated transition from left ventricular failure to right ventricular hypertrophy. Redox Biol. 2019;22.
Not in our library10.1016/j.redox.2019.101161 (opens in a new tab)
219.
Ying Z., Yue P., Xu X., Zhong M., Sun Q., Mikolaj M., Wang A., Brook R.D., Chen L.C., Rajagopalan S. Air pollution and cardiac remodeling: a role for RhoA/Rho-kinase. Am. J. Physiol. 2009;296:H1540-H1550.
Not in our library10.1152/ajpheart.01270.2008 (opens in a new tab)
220.
Wang H., Shen X., Tian G., Shi X., Huang W., Wu Y., Sun L., Peng C., Liu S., Huang Y., Chen X., Zhang F., Chen Y., Ding W., Lu Z. AMPKalpha2 deficiency exacerbates long-term PM2.5 exposure-induced lung injury and cardiac dysfunction. Free Radic. Biol. Med. 2018;121:202-214.
Not in our library10.1016/j.freeradbiomed.2018.05.008 (opens in a new tab)
221.
Perepu R.S., Dostal D.E., Garcia C., Kennedy R.H., Sethi R. Cardiac dysfunction subsequent to chronic ozone exposure in rats. Mol. Cell. Biochem. 2012;360:339-345.
Not in our library10.1007/s11010-011-1073-1 (opens in a new tab)
222.
Ambient air pollution and thrombosis · 2018
No notice
223.
Janssen N.A., Strak M., Yang A., Hellack B., Kelly F.J., Kuhlbusch T.A., Harrison R.M., Brunekreef B., Cassee F.R., Steenhof M., Hoek G. Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers. Occup. Environ. Med. 2015;72:49-56.
Not in our library10.1136/oemed-2014-102303 (opens in a new tab)
224.
Strak M., Hoek G., Godri K.J., Gosens I., Mudway I.S., van Oerle R., Spronk H.M., Cassee F.R., Lebret E., Kelly F.J., Harrison R.M., Brunekreef B., Steenhof M., Janssen N.A. Composition of PM affects acute vascular inflammatory and coagulative markers - the RAPTES project. PLoS One. 2013;8.
Not in our library10.1371/journal.pone.0058944 (opens in a new tab)
225.
Signorelli S.S., Oliveri Conti G., Zanobetti A., Baccarelli A., Fiore M., Ferrante M. Effect of particulate matter-bound metals exposure on prothrombotic biomarkers: a systematic review. Environ. Res. 2019;177.
Not in our library10.1016/j.envres.2019.108573 (opens in a new tab)
226.
Lucking A.J., Lundback M., Mills N.L., Faratian D., Barath S.L., Pourazar J., Cassee F.R., Donaldson K., Boon N.A., Badimon J.J., Sandstrom T., Blomberg A., Newby D.E. Diesel exhaust inhalation increases thrombus formation in man. Eur. Heart J. 2008;29:3043-3051.
Not in our library10.1093/eurheartj/ehn464 (opens in a new tab)
227.
Pettit A.P., Brooks A., Laumbach R., Fiedler N., Wang Q., Strickland P.O., Madura K., Zhang J., Kipen H.M. Alteration of peripheral blood monocyte gene expression in humans following diesel exhaust inhalation. Inhal. Toxicol. 2012;24:172-181.
Not in our library10.3109/08958378.2012.654856 (opens in a new tab)
228.
Chiarella S.E., Soberanes S., Urich D., Morales-Nebreda L., Nigdelioglu R., Green D., Young J.B., Gonzalez A., Rosario C., Misharin A.V., Ghio A.J., Wunderink R.G., Donnelly H.K., Radigan K.A., Perlman H., Chandel N.S., Budinger G.R., Mutlu G.M. beta(2)-Adrenergic agonists augment air pollution-induced IL-6 release and thrombosis. J. Clin. Investig. 2014;124:2935-2946.
Not in our library10.1172/jci75157 (opens in a new tab)
229.
Tabor C.M., Shaw C.A., Robertson S., Miller M.R., Duffin R., Donaldson K., Newby D.E., Hadoke P.W. Platelet activation independent of pulmonary inflammation contributes to diesel exhaust particulate-induced promotion of arterial thrombosis, Part. Fibre Toxicol. 2016;13:6.
Not in our library10.1186/s12989-016-0116-x (opens in a new tab)
230.
Nemmar A., Dhanasekaran S., Yasin J., Ba-Omar H., Fahim M.A., Kazzam E.E., Ali B.H. Evaluation of the direct systemic and cardiopulmonary effects of diesel particles in spontaneously hypertensive rats. Toxicology. 2009;262:50-56.
Not in our library10.1016/j.tox.2009.05.009 (opens in a new tab)
231.
Nemmar A., Al Dhaheri R., Alamiri J., Al Hefeiti S., Al Saedi H., Beegam S., Yuvaraju P., Yasin J., Ali B.H. Diesel exhaust particles induce impairment of vascular and cardiac homeostasis in mice: ameliorative effect of emodin. Cell. Physiol. Biochem. 2015;36:1517-1526.
Not in our library10.1159/000430315 (opens in a new tab)
232.
Nemmar A., Al-Salam S., Dhanasekaran S., Sudhadevi M., Ali B.H. Pulmonary exposure to diesel exhaust particles promotes cerebral microvessel thrombosis: protective effect of a cysteine prodrug l-2-oxothiazolidine-4-carboxylic acid. Toxicology. 2009;263:84-92.
Not in our library10.1016/j.tox.2009.06.017 (opens in a new tab)
233.
Nemmar A., Subramaniyan D., Ali B.H. Protective effect of curcumin on pulmonary and cardiovascular effects induced by repeated exposure to diesel exhaust particles in mice. PLoS One. 2012;7.
Not in our library10.1371/journal.pone.0039554 (opens in a new tab)
234.
Nemmar A., Subramaniyan D., Yasin J., Ali B.H. Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles, Part. Fibre Toxicol. 2013;10:14.
Not in our library10.1186/1743-8977-10-14 (opens in a new tab)
235.
Snow S.J., De Vizcaya-Ruiz A., Osornio-Vargas A., Thomas R.F., Schladweiler M.C., McGee J., Kodavanti U.P. The effect of composition, size, and solubility on acute pulmonary injury in rats following exposure to Mexico city ambient particulate matter samples. J. Toxicol. Environ. Health. 2014;77:1164-1182.
Not in our library10.1080/15287394.2014.917445 (opens in a new tab)
236.
Miller M.R., Raftis J.B., Langrish J.P., McLean S.G., Samutrtai P., Connell S.P., Wilson S., Vesey A.T., Fokkens P.H.B., Boere A.J.F., Krystek P., Campbell C.J., Hadoke P.W.F., Donaldson K., Cassee F.R., Newby D.E., Duffin R., Mills N.L. Correction to “inhaled nanoparticles accumulate at sites of vascular disease”. ACS Nano. 2017;11:10623-10624.
Not in our library10.1021/acsnano.7b06327 (opens in a new tab)
237.
Sangani R.G., Soukup J.M., Ghio A.J. Metals in air pollution particles decrease whole-blood coagulation time. Inhal. Toxicol. 2010;22:621-626.
Not in our library10.3109/08958371003599037 (opens in a new tab)
238.
Metassan S., Charlton A.J., Routledge M.N., Scott D.J., Ariens R.A. Alteration of fibrin clot properties by ultrafine particulate matter. Thromb. Haemost. 2010;103:103-113.
Not in our library10.1160/th09-05-0330 (opens in a new tab)
239.
Pan X., Gong Y.Y., Xu Y., Ariens R.A.S., Routledge M.N. Urban particulate matter induces changes in gene expression in vascular endothelial cells that are associated with altered clot structure in vitro. Thromb. Haemost. 2018;118:266-278.
Not in our library10.1160/th17-05-0362 (opens in a new tab)
240.
Snow S.J., Cheng W., Wolberg A.S., Carraway M.S. Air pollution upregulates endothelial cell procoagulant activity via ultrafine particle-induced oxidant signaling and tissue factor expression. Toxicol. Sci. 2014;140:83-93.
Not in our library10.1093/toxsci/kfu071 (opens in a new tab)
241.
Joubert J., Cumming T.B., McLean A.J. Diversity of risk factors for stroke: the putative roles and mechanisms of depression and air pollution. J. Neurol. Sci. 2007;262:71-76.
Not in our library10.1016/j.jns.2007.06.027 (opens in a new tab)
242.
Wellenius G.A., Burger M.R., Coull B.A., Schwartz J., Suh H.H., Koutrakis P., Schlaug G., Gold D.R., Mittleman M.A. Ambient air pollution and the risk of acute ischemic stroke. Arch. Intern. Med. 2012;172:229-234.
Not in our library10.1001/archinternmed.2011.732 (opens in a new tab)
243.
Hong Y.C., Lee J.T., Kim H., Kwon H.J. Air pollution: a new risk factor in ischemic stroke mortality. Stroke. 2002;33:2165-2169.
Not in our library10.1161/01.str.0000026865.52610.5b (opens in a new tab)
244.
Fiorito G., Vlaanderen J., Polidoro S., Gulliver J., Galassi C., Ranzi A., Krogh V., Grioni S., Agnoli C., Sacerdote C., Panico S., Tsai M.Y., Probst-Hensch N., Hoek G., Herceg Z., Vermeulen R., Ghantous A., Vineis P., Naccarati A., dagger E.X.c. Oxidative stress and inflammation mediate the effect of air pollution on cardio- and cerebrovascular disease: a prospective study in nonsmokers. Environ. Mol. Mutagen. 2018;59:234-246.
Not in our library10.1002/em.22153 (opens in a new tab)
245.
Morgan T.E., Davis D.A., Iwata N., Tanner J.A., Snyder D., Ning Z., Kam W., Hsu Y.T., Winkler J.W., Chen J.C., Petasis N.A., Baudry M., Sioutas C., Finch C.E. Glutamatergic neurons in rodent models respond to nanoscale particulate urban air pollutants in vivo and in vitro. Environ. Health Perspect. 2011;119:1003-1009.
Not in our library
246.
Rizzo A.M., Corsetto P.A., Farina F., Montorfano G., Pani G., Battaglia C., Sancini G., Palestini P. Repeated intratracheal instillation of PM10 induces lipid reshaping in lung parenchyma and in extra-pulmonary tissues. PLoS One. 2014;9.
Not in our library10.1371/journal.pone.0106855 (opens in a new tab)
247.
Lucchini R.G., Dorman D.C., Elder A., Veronesi B. Neurological impacts from inhalation of pollutants and the nose-brain connection. Neurotoxicology (Little Rock). 2012;33(4):838-841.
Not in our library10.1016/j.neuro.2011.12.001 (opens in a new tab)
248.
Ejaz S., Anwar K., Ashraf M. MRI and neuropathological validations of the involvement of air pollutants in cortical selective neuronal loss. Environ. Sci. Pollut. Res. Int. 2014;21:3351-3362.
Not in our library10.1007/s11356-013-2294-5 (opens in a new tab)
249.
Wallenborn J.G., Schladweiler M.C., Nyska A., Johnson J.A., Thomas R., Jaskot R.H., Richards J.H., Ledbetter A.D., Kodavanti U.P. Cardiopulmonary responses of Wistar Kyoto, spontaneously hypertensive, and stroke-prone spontaneously hypertensive rats to particulate matter (PM) exposure. J. Toxicol. Environ. Health. 2007;70:1912-1922.
Not in our library10.1080/15287390701551233 (opens in a new tab)
250.
Translocation and potential neurological effects of fine and ultrafine particles a critical update. · 2006
No notice
251.
Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice · 2013
No notice
252.
Dringen R. Metabolism and functions of glutathione in brain. Prog. Neurobiol. 2000;62:649-671.
Not in our library10.1016/s0301-0082(99)00060-x (opens in a new tab)
253.
Kim Y.D., Lantz-McPeak S.M., Ali S.F., Kleinman M.T., Choi Y.S., Kim H. Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells. Environ. Toxicol. Pharmacol. 2014;37:954-959.
Not in our library10.1016/j.etap.2014.03.008 (opens in a new tab)
254.
Lawal A.O., Zhang M., Dittmar M., Lulla A., Araujo J.A. Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals. Toxicol. Appl. Pharmacol. 2015;284:281-291.
Not in our library10.1016/j.taap.2015.01.010 (opens in a new tab)
255.
Lin Y.L., Chang H.C., Chen T.L., Chang J.H., Chiu W.T., Lin J.W., Chen R.M. Resveratrol protects against oxidized LDL-induced breakage of the blood-brain barrier by lessening disruption of tight junctions and apoptotic insults to mouse cerebrovascular endothelial cells. J. Nutr. 2010;140:2187-2192.
Not in our library10.3945/jn.110.123505 (opens in a new tab)
256.
Nemmar A., Al-Salam S., Beegam S., Yuvaraju P., Ali B.H. Thrombosis and systemic and cardiac oxidative stress and DNA damage induced by pulmonary exposure to diesel exhaust particles and the effect of nootkatone thereon. Am. J. Physiol. Heart Circ. Physiol. 2018;314:H917-H927.
Not in our library10.1152/ajpheart.00313.2017 (opens in a new tab)
257.
Romieu I., Castro-Giner F., Kunzli N., Sunyer J. Air pollution, oxidative stress and dietary supplementation: a review. Eur. Respir. J. 2008;31:179-197.
Not in our library10.1183/09031936.00128106 (opens in a new tab)
258.
Tong H. Dietary and pharmacological intervention to mitigate the cardiopulmonary effects of air pollution toxicity. Biochim. Biophys. Acta. 2016;1860:2891-2898.
Not in our library10.1016/j.bbagen.2016.05.014 (opens in a new tab)
259.
Lim C.C., Hayes R.B., Ahn J., Shao Y., Silverman D.T., Jones R.R., Thurston G.D. Mediterranean diet and the association between air pollution and cardiovascular disease mortality risk. Circulation. 2019;139:1766-1775.
Not in our library10.1161/circulationaha.118.035742 (opens in a new tab)
260.
Romieu I., Garcia-Esteban R., Sunyer J., Rios C., Alcaraz-Zubeldia M., Velasco S.R., Holguin F. The effect of supplementation with omega-3 polyunsaturated fatty acids on markers of oxidative stress in elderly exposed to PM(2.5). Environ. Health Perspect. 2008;116:1237-1242.
Not in our library10.1289/ehp.10578 (opens in a new tab)
261.
Jiang Y., Wang C., Lin Z., Niu Y., Xia Y., Liu C., Chen C., Ge Y., Wang W., Yin G., Cai J., Chen B., Chen R., Kan H. Alleviated systemic oxidative stress effects of combined atmospheric oxidant capacity by fish oil supplementation: a randomized, double-blinded, placebo-controlled trial. Ecotoxicol. Environ. Saf. 2019;184.
Not in our library10.1016/j.ecoenv.2019.109598 (opens in a new tab)

Cited by papers we hold 1

Cardiovascular health impacts of wildfire smoke exposure · 2021
No notice

Questions about this paper

We email you if it is retracted, withdrawn, corrected or flagged.

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.