Ozaki et al. showed that chronic overexpression of eNOS does not inhibit, but accelerates, atherosclerosis under hypercholesterolemia and that eNOS dysfunction appears to play important roles in the progression of atherosclerosis in apoE-deficient/eNOS-overexpressing mice (apoE-KO/eNOS-Tg mice). This evidence concerns the gene APOE and familial hypercholesterolemia.