EDN1 and endothelial dysfunction: 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