Our data are in contrast to findings by Chang et al. who demonstrated that low-dose simvastatin treatment with 20 mg per day even for the short period of 5–7 days in patients with valvular heart disease was sufficient to induce HDL-mediated phosphorylation of Akt and eNOS at Ser1177 and to inhibit eNOS phosphorylation at the Thr495 site in cultured human umbilical vein endothelial cells, resulting in enhanced NO production. This evidence concerns the gene NOS3 and heart valve disorder.