To that end, we investigated the effects and underlying molecular mechanisms exerted by circulating SIRT1 on lipid metabolism, inflammation, and plaque formation in ApoE−/− mice fed on high-cholesterol diet and assessed the translational value of our experimental findings by measuring SIRT1 and PCSK9 in plasma of patients with acute coronary syndrome (ACS), an acute but common complication of ASCVD. This evidence concerns the gene PCSK9 and acute coronary syndrome.