This activation influences key signaling pathways, including the mTOR-p70S6K, JNK, and TGF-β/Smad3, effectively reducing ISO-induced myocardial hypertrophy and fibrosis rat heart failure in vitro and in vivo models, and confirmed the targeting of 2-APQC in SIRT3 knockout mice. This evidence concerns the gene SMAD3 and heart failure.