In aggregate with our findings showing increased TGF-β1 secretion by PAH PAVSMC, these data demonstrate that Smad2 and 3 are down-regulated in human PAH PAVSMC compared to controls and suggest autocrine mechanism of Smad2 and Smad3 down-regulation due to prolonged TGF-β1 exposure. The gene discussed is SMAD3; the disease is pulmonary arterial hypertension.