In addition to an abnormal vasodilator function, we have demonstrated that patients with hypertension [4], hypercholesterolemia [5], and type 2 diabetes [6] have higher vascular ET-1 activity, likely due to increased ET-1 gene expression triggered by a host of factors including angiotensin 2, insulin, oxidized LDL, and inflammatory cytokines [17]. This evidence concerns the gene INS and familial hypercholesterolemia.