Single‐cell sequencing of mouse heart cellular heterogeneity in hypercholesterolemia reveals the mechanism of myocardial damage

Single-cell sequencing of mouse heart cellular heterogeneity in hypercholesterolemia reveals the mechanism of myocardial damageTo the Editor, Cardiovascular diseases are a leading cause of death worldwide, accounting for approximately one-third of all deaths. 1 As a major risk factor for cardiovascular disease, hypercholesterolemia causes direct myocardial damage.Previous studies have shown that hypercholesterolemia may cause myocardial reactive oxidative stress and mitochondrial dysfunction, ultimately resulting in myocardial damage.2,3 Nevertheless, there is still limited information on the specific molecular mechanisms that underlie this condition.Inflammation is a key process in cardiovascular diseases associated with hypercholesterolemia, such as atherosclerosis, and includes the activation of T lymphocytes.4 Single-cell RNA sequencing is an essential research method for detecting the cellular changes and molecular processes of the heart.5 Currently, single-cell sequencing studies in hypercholesterolemia have mainly focused on the changes in inflammatory cell subtypes in atherosclerotic plaques, 6 and the changes in the cellular composition in the heart remain unknown.Therefore, we used single-cell sequencing to detect all heart cells in the early and late stages of disease to explore the molecular mechanism of myocardial damage.First, we utilized Apoe -/-mice fed a high-cholesterol diet to establish a hypercholesterolemia model.In the process, the mouse serum lipoprotein index of TC and LDL increased significantly, and HE and ORO staining indicated that lipid levels increased (Figure S1A-E).Then, we identified 12 cell clusters of heart tissues according to the marker genes via single-cell sequencing (Figure 1A-D).When ordering these clusters according to abundance, the most abundant cell population was fibroblasts.Inflammatory cells, such as myeloid cells, B cells and T cells, increased in the disease group (Figure 1E).Next, cardiomyocytes were identified based on the cardiomyocyte marker genes Ttn and Tnnt2 (Figure 1D).

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