PECAM EMPs regulate apoptosis in pulmonary microvascular endothelial cells in COPD by activating the Akt signaling pathway

Introduction Endothelial microparticles (EMPs) are partly associated with the progress of chronic obstructive pulmonary disease (COPD). We sought to measure the levels of EMPs in COPD patients and in human pulmonary microvascular endothelial cells (HPMECs) exposed to cigarette smoking extract (CSE) to elucidate the potential mechanisms of their action. Methods We obtained prospectively blood EMPs from 30 stable COPD patients and 20 non-COPD volunteers. EMP subpopulations were determined by flow cytometry in platelet-free plasma according to the expression of membrane specific antigens. Cell growth, proliferation, apoptosis and the expression of protein kinase B (Akt) in HPMECs after exposure to PECAM EMPs were assessed. After intervention with an antioxidant (Eukarion-134, EUK-134), apoptosis and the expression of Akt in HPMECs were also measured. Results Unlike those of MCAM EMPs, VE-cadherin, PECAM and E-selectin EMP values were significantly higher in the stable COPD patients than in the non-COPD volunteers (p<0.05). Only PECAM EMPs were higher in HPMECs exposed to CSE (p<0.05). Further, in vitro studies showed that the apoptosis rate and expression of cleaved caspase 3/9 in HPMECs increased in a dose- and time-independent manner with PECAM EMPs. The expression of phospho-Akt (p-Akt) decreased in a time-independent manner with PECAM EMPs (p<0.05). Compared with the control group, the early apoptosis rate of HPMECs was higher, and the expression of p-Akt was lower in both the PECAM EMP group and EUK-134 + PECAM EMP group (p<0.05). The apoptosis rate declined markedly, and the expression of p-Akt was higher in the EUK-134 + PECAM EMP group, compared with the PECAM EMPs group (p<0.05). Conclusions The present results suggest that PECAM EMPs positively regulate apoptosis in HPMECs in COPD, likely by decreasing Akt phosphorylation and can be protected by antioxidants.

Abstract licence: CC BY-ND

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