Statins modulate endothelial transcriptional profile by inhibiting EZH2

Statins protect against the development of atherosclerosis via cholesterol-dependent and –independent mechanisms. Understanding the molecular mechanisms mediating simvastatin induced atheroprotective effects is critical for designing anti-atherosclerotic agents. Here, we showed that simvastatin decreases the expression of the Polycomb methyltransferase EZH2 in endothelial cells. To better understand the influence of the simvastatin-induced EZH2 downregulation on endothelial transcriptome, we performed RNA-sequencing study to evaluate differential gene expression after overexpression of EZH2 in the presence of simvastatin treatment. We found simvastatin treatment altered a subset of genes that can be rescued with EZH2 overexpression. Therefore, simvastatin treated endothelial cells display an atheroprotective phenotype by downregulating EZH2.