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Cellular composition of human early and advanced coronary atherosclerotic lesions

Sharysh, D.; Markov, A.; Grigoryeva, E. S.; Savelieva, O. E.; Sleptcov, A. A.; Zarubin, A. A.; Nazarenko, M. S.

2021-10-07 cardiovascular medicine
10.1101/2021.10.07.21264647 medRxiv
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ObjectiveHere, we identify and quantify leukocytes, macrophages, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) with contractile and macrophage-like phenotypes by flow cytometry to compare human early and advanced coronary atherosclerotic plaques. Approach and ResultsSixteen coronary atherosclerotic lesions of 6 patients (3 women, 3 men, age 82 {+/-} 9 years), including one case of restenosis after coronary stenting, were collected at autopsy. The cause of death of all patients was acute myocardial infarction. The lesions were categorized into early (EALs, n = 5) and advanced (AALs, n = 11) atherosclerotic stages. We analyzed a cell suspension stained with antibodies against CD45, CD68, CD31, and SMA (ACTA2). We noted a decrease in the number of CD45+ cells and an increase in the CD45+CD68+ subpopulation of leukocytes from EALs to AALs. Numbers of CD45-SMA+CD68+ cells positively correlated with the CD45+CD68+ macrophage number (r = 0.81; {rho} = 0.64; p < 0.05) and the histological type of an atherosclerotic lesion (r = 0.81; {rho} = 0.87; p < 0.05). As an interesting case, we analyzed cellular composition of the stented coronary artery and revealed significantly greater numbers of macrophages, SMA+CD68+ VSMCs, and ECs in comparison with nonstented plaques. ConclusionsHuman early and advanced coronary atherosclerotic lesions differ in their counts of leukocytes and leukocyte subpopulations. For the first time, SMA+CD68+ VSMCs were identified in early atherosclerotic stages of coronary arteries. Additionally, the restenotic coronary lesion contains mostly cells and is enriched in ECs, macrophages, and SMA+CD68+ VSMCs in particular.

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