UC San Diego

Coronary artery disease (CAD) remains one of the leading causes of death in the US and represents a mechanistically complex disease. GWAS (Genome Wide Association Studies) have identified SNPs (Single Nucleotide Polymorphisms) within the 9p21 locus as having the greatest correlation with increased susceptibility towards CAD (Samani, Schunkert., 2008). However, the 9p21 locus is a non-coding region, making the mechanism through which these SNPs result in CAD less clear. Vascular smooth muscle cells (VSMCs), which typically function to regulate vascular tone, are known to switch from a contractile to a synthetic phenotype during CAD progression and vascular remodeling. We hypothesize that the 9p21 risk variants result in a more prominent synthetic population compared to the contractile phenotype and that these two phenotypes can be isolated utilizing a shear assay, which sorts cells based on adhesion strength. Specifically, we aim to show that the weakly adherent is comprised of more synthetic cells and the strongly adherent are comprised of more contractile cells by measuring differences in the expression of contractility and proliferation markers.