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 αSMA (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−αSMA+CD68+ cells positively correlated with the CD45+CD68+ macrophage number (r = 0.81; ρ = 0.64; p < 0.05) and the histological type of an atherosclerotic lesion (r = 0.81; ρ = 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, αSMA+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, αSMA+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 αSMA+CD68+ VSMCs in particular.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
RSC #17-75-10146: biomaterial collection and storage, tissue disaggregation RFBR #20-315-90076: flow cytometry and statistical analysis
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Local Biomedical Ethics Committee of the Research Institute of Medical Genetics, Tomsk National Research Medical Center gave ethical approval for this work (protocol No. 158).
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Data Availability
All the data have been presented in the manuscript
Abbreviations
- VSMCs
- Vascular smooth muscle cells
- ECS
- Endothelial cells
- DCs
- Dendritic cells
- ScRNA-Seq
- Single-cell RNA sequencing
- EAL
- Early atherosclerotic lesion
- AAL
- Advanced atherosclerotic lesion