Cellular composition of human early and advanced coronary atherosclerotic lesions

Abstract

Objective: Here, 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 Results: Sixteen 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 aSMA (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-aSMA+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 the cellular composition of the stented coronary artery and revealed significantly greater numbers of macrophages, aSMA+CD68+ VSMCs, and ECs in comparison with nonstented plaques. Conclusions: Human early and advanced coronary atherosclerotic lesions differ in their counts of leukocytes and leukocyte subpopulations. For the first time, aSMA+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 aSMA+CD68+ VSMCs in particular.