SMAD3 and Myocardial fibrosis: SIRT2 deficiency exacerbates angiotensin II-induced myocardial fibrosis.102 SIRT3 can activate GSK3β through K15 deacetylation, which in turn phosphorylates SMAD3 and leads to its degradation, thereby preventing TGF β-induced fibrosis.103 In contrast, SIRT4 depletion attenuated angiotensin II-induced myocardial fibrosis.104 Shen et al.105 found that SIRT6 levels were significantly reduced in phenylephrine-induced neonatal rat cardiomyocytes, which was associated with increased acetyltransferase P300 levels and cardiomyocyte hypertrophy.