SIRT1 and atherosclerosis: Mounting evidence has demonstrated that intracellular activation of SIRT1 protects against atherosclerosis.30–33 Indeed, overexpression of Sirt1 in endothelial cells of ApoE−/− mice fed on a high-fat diet promotes endothelium-dependent vasodilation and protects against atherosclerosis by increasing eNOS activity.34 Small molecule activators of intracellular SIRT1 reduced total cholesterol35 and especially plasma LDL-C levels.17 However, these studies provided limited mechanistic insight into the effects of SIRT1 on cholesterol metabolism and atherosclerosis.