Consistent with disease-related overactivation of SMAD3 in the pulmonary vasculature, perivascular regions of ZSF-Su rat lung were found to contain increased immunostaining for activin A and GDF11 (Supplementary Figure 9), prominent activators of SMAD2/3 signaling previously implicated in PAH (15). This evidence concerns the gene SMAD3 and pulmonary arterial hypertension.