EDN1 and Myocardial fibrosis: Myocardial fibrosis was also elevated in cardiac tissue of SIRT3 knockout mice, as reported in other studies,28,31 and consistent with this, the expression of TGF-β, ATF4, and EDN-1 was inhibited by SIRT3 overexpression in AC16 cells and in neonatal rat cardiomyocytes.