Deciphering the panvascular immune landscape of atherosclerosis

Abstract Atherosclerosis (AS) is a key pathological process leading to cardiovascular diseases, with its occurrence closely associated with the immune microenvironment, yet there remains a gap in detailed studies that explore these effects across different artery beds. With panvascular perspective, this study goes beyond traditional single‐site analysis to investigate AS plaques in five key arterial regions: the abdominal aorta, infrapopliteal artery, femoral artery, carotid artery, and coronary artery. We performed immune infiltration analysis and differential gene analysis, and obtained key genes for AS diagnosis through multiple feature selection, and performed drug screening targeting these genes. Among these diagnostic genes identified were genes such as CCR1, LPL, which has been shown to play an important role in AS, and genes such as BDNF, whose role in AS is not yet clear. Our findings highlight unique patterns of immune gene expression and immune cell infiltration at each site, providing new insights into the complex nature of AS. By identifying distinct molecular signatures, we uncover potential diagnostic markers and therapeutic targets. We validated these results in single‐cell datasets and noted different patterns of macrophage activation in carotid and coronary arteries. We also investigated the expression patterns of these diagnostic genes in venous sclerosis disease, revealing possible similarities between AS and venous sclerosis in the immune microenvironment. This study highlights the variability of the immune microenvironment of AS at different sites and explores the differences in interactions between immune cells, providing new ideas for the mechanisms of AS from a panvascular perspective.