SMAD3 and heart failure: More recently, activated fibroblast-specific deletion of Tgfbr1/2 or Smad3, but not Smad2, was shown to reduce cardiac fibrosis in a model of pressure overload-induced heart failure (transverse aortic constriction, TAC), confirming that TGF-β signaling is a nodal regulator of profibrotic function in the heart [5].