The present findings that ET-1 is up-regulated in PASMCs from FpnC326Yfl/fl SMMHC-CreERT2+ mice, in the serum of healthy volunteers following acute hypoxia exposure, and in the supernatants of PASMCs from PAH patients are all consistent with this long-recognized role. This evidence concerns the gene MYH11 and pulmonary arterial hypertension.