The Landscape of Single Cells in Atherosclerotic Plaques

Abstract

Atherosclerosis, the underlying driver of major cardiovascular events such as myocardial infarc tion and stroke, is marked by chronic inflammation and lipid accumulation within arterial walls, leading to the formation of plaque lesions. Despite its global burden, many cellular mechanisms underpinning plaque ini tiation, progression, and destabilization remain incompletely understood. Notably, immune-mediated trans formations of vascular smooth muscle cells (SMCs), endothelial cells (ECs), and fibroblasts during plaque development are areas of intense investigation. Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of tissue complexity by revealing cell-type heterogeneity at unparalleled resolution. In our study, we utilize a comprehensive scRNA-seq reference atlas that spans over 250,000 cells derived from carotid, coronary, and femoral artery samples. The atlas provides hierarchical annotations at two levels of granularity: Level 1 defines 13 broad cell classes, while Level 2 refines these into more specific subtypes. Using this atlas as a reference, we apply cell2location-based spot deconvolution on 10x Genomics Visium spatial transcriptomics data from coronary artery plaques. This integration allows us to map the spatial organization of these diverse cell types in early versus advanced lesions. Our results reveal that while both immune and structural cells are present across all stages, immune populations are enriched in advanced lesions, highlighting the pivotal role of inflammation in disease progression.