These results are in accordance with several studies showing that endothelial dysfunction in pulmonary vasculature, disrupted balance of vasoactive substances (endothelin-1 and NO, among others) and impaired endothelium-dependent pulmonary artery relaxation are observed prior to vascular remodeling or plexiform lesions in humans with PH [50] and animal models [51], [52]. Here, EDN1 is linked to endothelial dysfunction.