For example, significant increases in TGF-β1 and P-Smad3 levels have been detected in a rat model of pulmonary hypertension induced by hypoxia [24], and the significant downregulation of BMP/Smad1/5 and upregulation of TGF-β/Smad2/3 after 24 h of hypoxic treatment has been reported in primary cultured rat PASMCs [25]. This evidence concerns the gene SMAD3 and pulmonary hypertension.