Imbalanced signaling by the transforming growth factor-β (TGF-β) superfamily contributes extensively to pathologic vascular remodeling in PAH, with overactive, pro-proliferative SMAD2/3 signaling occurring along with deficient, antiproliferative SMAD1/5/8 signaling (14). Here, SMAD2 is linked to pulmonary arterial hypertension.