EPAS1 and pulmonary hypertension: Although pulmonary vasodilator therapies are not standard for COPD-PH outside trials, preclinical HIF-2α inhibition (e.g., PT2385, PT2567; genetic reversal of HIF-2–driven remodeling) can attenuate established pulmonary hypertension and reverse vascular changes while identifying the HIF-2α axis as a tractable target in patients with a vascular endotype, awaiting biomarker-guided enrichment and clinical validation [115].