Genome-Wide Search Links Senescence-Associated Secretory Proteins With Susceptibility for Coronary Artery Disease in Mouse and Human.

This article investigates how senescence-associated secretory phenotype (SASP) proteins derived from vascular cells contribute to coronary artery disease (CAD) susceptibility, focusing on the role of Cystatin C (CST3). Integrating gene expression and genome-wide association data, the study identifies CST3 as a SASP protein upregulated in senescent vascular endothelial and smooth muscle cells, aged arteries, and early atherosclerosis. Functional assays demonstrate that CST3 enhances monocyte–endothelial cell adhesion, a key event in atherosclerosis initiation. Additionally, two ligand–receptor pairs, COL4A1-ITGA1 and LPL-LRP1, are identified as important signaling pathways linked to cell adhesion, inflammation, extracellular matrix organization, and lipid metabolism in vascular aging and CAD. These findings suggest that vascular cell-derived SASP proteins, particularly CST3 and the identified ligand–receptor interactions, play significant roles in the pathogenesis of CAD.