In the present study, we crossed miR-33-deficient mice (miR-33−/−) with apoE-deficient mice (Apoe−/−) to examine the impact of miR-33 deletion on the progression of atherosclerosis and demonstrated that genetic loss of miR-33 raises circulating HDL-C and decreases atherosclerotic plaque size. This evidence concerns the gene APOE and atherosclerosis.