Single-cell RNA sequencing (scRNA-seq) and its insights into cellular heterogeneity in atherosclerosis

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cellular diversity in human biology, providing novel insights into disease mechanisms. In cardiovascular disease (CVD), scRNA-seq enables precise mapping of complex cell populations, uncovering unique cell types and states that influence disease progression and suggest new therapeutic targets. In atherosclerosis (AS), scRNA-seq has redefined plaque pathology by identifying distinct cell types, including endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts, macrophages, T cells, and B cells, each with specific roles in plaque stability, inflammation, and disease progression. In our review, we summarized these major cellular populations and their cellular heterogeneity in non-diseased and atherosclerotic aorta, as identified by scRNA-seq in mice and human tissues. We discussed conserved and species-specific subpopulations, their defining markers, and their functional implications in plaque progression. In addition, we integrated findings from scRNA-seq with experimental studies to highlight key molecular targets with therapeutic potential. In the future, these insights offer a refined cellular and molecular framework of atherosclerosis and may help the development of targeted interventions to promote plaque stabilization and reduce cardiovascular risk.