Several lines of evidence suggest that decreased eNOS phosphorylation is a molecular mechanism linking aberrant metabolism and vascular dysfunction: (i) eNOS phosphorylation is diminished in diabetes, hypercholesterolemia, and atherosclerosis (40–42), (ii) anti-diabetic drugs including statins and PPAR agonists increase eNOS phosphorylation (37), and (iii) signaling molecules including insulin, IGF-1, and leptin increase eNOS phosphorylation (39). This evidence concerns the gene IGF1 and familial hypercholesterolemia.