SMAD3 and pulmonary arterial hypertension: In agreement with recently published studies, showing that Smad3 is down-regulated in PAVSMC in advanced PAH [32], we found that human PAH PAVSMC have marked reduction of active P-Ser465/467 Smad2 and P-Ser423/425 Smad3 compared to controls, as seen in Figure 2A–C.