SMAD3 and cardiac hypertrophy: However, STA-5326 does not directly stimulate SIRT3 to treat myocardial hypertrophy.70 Resveratrol can activate SIRT3 and reduce cardiac hypertrophy and fibrosis in mice through the TGF-β/Smad3 pathway.62 However, these compounds are not satisfactory in terms of therapeutic effects or stimulation of SIRT3.