The mechanisms include the reactive oxygen species-mediated eNOS uncoupling, loss of eNOS-derived NO bioavailability, hyperglycemia-promoted apoptosis of vascular endothelial cells (ECs) in diabetes, which ultimately leads to impaired endothelium-dependent vessel relaxation, a general biomarker of endothelial dysfunction (11–15). This evidence concerns the gene NOS3 and endothelial dysfunction.