EDN1 and pulmonary arterial hypertension: Increased extracellular ligands (e.g., endothelin-1, spermine, PDGF) and up-regulated expression of various GPCRs (e.g., endothelin receptor A, Ca2+-sensing receptors) and TKRs (PDGFR) have been implicated in the development and progression of pulmonary vascular remodeling in patients with PAH 35, 46, 47.