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. This evidence concerns the gene PDGFRB and pulmonary arterial hypertension.