Among these triggers, hypoxia and the actions of its master transcription factors of hypoxia, HIF-1α and HIF-2α, are well-recognized insults in multiple PH subtypes, including pulmonary arterial hypertension (PAH, WHO Group 1) (Bonnet et al, 2006; Fijalkowska et al, 2010; Farha et al, 2011; Marsboom et al, 2012) as well as PH associated with hypoxic lung diseases (WHO Group 3) (as reviewed by Tuder et al, 2013). This evidence concerns the gene EPAS1 and pulmonary arterial hypertension.