The 9p21.3 Coronary Artery Disease Risk Locus Drives Vascular Smooth Muscle Cells to an Osteochondrogenic State

Our study provides new insights into the mechanism of the 9p21.3 risk locus and defines its previously undescribed role in driving a disease-prone transcriptional and functional state in VSMCs concordant with an osteochondrogenic-like state. Our data suggest that the 9p21.3 risk haplotype likely promotes arterial calcification, through altered expression of <i>ANRIL</i>, in a cell type-specific and cell-autonomous manner, providing insight into potential risk assessment and treatment for carriers.