Mechanistically, oxidative stress-mediated reduction in sirtuin-3 (SIRT3) activity (previously implicated in PAH pathogenesis) increases HIF-1α activity, which could explain the augmentation in glutamine utilization by pulmonary microvascular ECs from BMPR2-mutant PAH mice [57]. The gene discussed is HIF1A; the disease is pulmonary arterial hypertension.