A Single-Cell Analysis Reveals Macrophage Heterogeneity Driving Plaque Vulnerability in Coronary and Carotid Arteries

AIM: Acute coronary syndrome (ACS) and ischemic stroke are major life-threatening conditions caused by atherosclerosis. Although the mechanisms of atherosclerosis appear to be broadly similar across different vascular beds, growing evidence suggests that there are morphological and histological differences between coronary and carotid atherosclerosis. To identify disease-specific therapeutic strategies, we aimed to compare ACS and chronic coronary syndrome (CCS) in coronary artery disease, and symptomatic and asymptomatic carotid artery disease. METHODS: We analyzed our own single-cell RNA sequencing dataset for coronary artery disease (GSE184073) and a publicly available dataset for carotid artery disease (GSE253903). Myeloid cells were extracted from these datasets and comparative analyses were performed using metabolic profiling and an RNA velocity analysis. RESULTS: foamy macrophages expressing MMP19. CONCLUSIONS: inflammatory macrophages in carotid and coronary artery diseases, which is associated with plaque vulnerability. Notably, the distinct activation of the glycolytic pathway in a separate macrophage subset suggests that tailored therapeutic strategies may be necessary to effectively address plaque vulnerability in each vascular bed.