The vascular profile of irreversible shunt-induced PAH in rats was further corroborated in human lung explant tissue from patients with irreversible PAH-CHD vs. controls, confirming markers of senescence (survivin, p16ink4A and p21cip1) in human PAH-CHD tissue, and higher vulnerability to senescence of PAH-CHD tissue derived endothelial cells in response to shear stress. The gene discussed is CDKN2A; the disease is pulmonary arterial hypertension.