Mechanistically, endothelial dysfunction is evident in both PAH and atherosclerosis in the form of impaired endothelium-dependent and -independent vasorelaxation.17, –19 Endothelin (ET)-1 is a potent vasoconstrictor formed by the conversion of Big ET-1 to ET-1 by ET-converting enzymes.20 ET-1 production and secretion can be regulated by inflammatory cytokines,21,22 hypoxia, and glucose,23, –25 and is increased in the vessel wall of experimental models26 and human atherosclerotic lesions26,27 and PAH.28 The gene discussed is EDN1; the disease is atherosclerosis.