Single-cell Technologies in Atherosclerosis: Uncovering Cellular Heterogeneity, Mechanisms, and Therapeutic Opportunities

PURPOSE OF REVIEW: This review highlights recent advances in single-cell analysis technologies and their application in clarifying the cellular and molecular complexity of atherosclerosis, redefining our understanding of vascular biology and immune cell functioning within the atherosclerotic plaque. RECENT FINDINGS: Single-cell RNA sequencing (scRNA-seq), single-cell ATAC-seq, and spatial transcriptomics have revealed an unforeseen diversity of immune and vascular cell states in human and experimental prototypes of atherosclerosis. These techniques have led to the finding of novel macrophage and smooth muscle cell (SMC) phenotypes, distinct endothelial dysfunction signatures, and oligoclonal T cell populations. By integrating transcriptomic, epigenomic, proteomic, and spatial data, researchers have clarified key mechanisms of disease progression and identified cell-specific molecular pathways responsive to targeted therapy. Single-cell methods are changing our understanding of atherosclerosis by determining the heterogeneity, plasticity, and functional states of plaque-resident cells. These understandings contribute for the development of novel biomarkers, precision diagnostics, and targeted immunomodulatory strategies, with the ultimate goal of improving risk stratification and personalized treatment in atherosclerotic cardiovascular disease.