Evidence of the pathogenic importance of disordered O2-sensing pathways in PAH includes the observations that therapeutic overexpression of Kv1.5 (Michelakis et al., 2001; Brevnova et al., 2004; Bonnet et al., 2006) or dominant negative HIF-1α inhibition (Bonnet et al., 2006) restores PASMC membrane polarity and apoptosis in vitro. Dichloroacetate, an inhibitor of PDK that restores oxidative glucose metabolism in PAH PASMC, also restores Kv1.5 expression in animal models of PAH and regresses adverse pulmonary remodeling and improves hemodynamics (Bonnet et al., 2006). This evidence concerns the gene KCNA5 and pulmonary arterial hypertension.