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Our present study investigates whether hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) attenuated myocardial fibrosis and explores the possible role of SIRT3 on the protective effects. Neonatal rat cardiac fibroblasts were pretreated with NaHS followed by angiotensin II (Ang II) stimulation. SIRT3 was knocked down with siRNA technology. SIRT3 promoter activity and expression, as well as mitochondrial function, were measured. Male wild\u2010type (WT) and SIRT3 knockout (KO) mice were intraperitoneally injected with NaHS followed by transverse aortic constriction (TAC). Myocardium sections were stained with Sirius red. Hydroxyproline content, collagen I and collagen III, <jats:italic>\u03b1<\/jats:italic>\u2010smooth muscle actin (<jats:italic>\u03b1<\/jats:italic>\u2010SMA), and dynamin\u2010related protein 1 (DRP1) expression were measured both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. We found that NaHS enhanced SIRT3 promoter activity and increased SIRT3 mRNA expression. NaHS inhibited cell proliferation and hydroxyproline secretion, decreased collagen I, collagen III, <jats:italic>\u03b1<\/jats:italic>\u2010SMA, and DRP1 expression, alleviated oxidative stress, and improved mitochondrial respiration function and membrane potential in Ang II\u2010stimulated cardiac fibroblasts, which were unavailable after SIRT3 was silenced. <jats:italic>In vivo<\/jats:italic>, NaHS reduced hydroxyproline content, ameliorated perivascular and interstitial collagen deposition, and inhibited collagen I, collagen III, and DRP1 expression in the myocardium of WT mice but not SIRT3 KO mice with TAC. Altogether, NaHS attenuated myocardial fibrosis through oxidative stress inhibition via a SIRT3\u2010dependent manner.<\/jats:p>","DOI":"10.1155\/2021\/9925771","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T20:16:49Z","timestamp":1632514609000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Hydrogen Sulfide Attenuates Angiotensin II\u2010Induced Cardiac Fibroblast Proliferation and Transverse Aortic Constriction\u2010Induced Myocardial Fibrosis through Oxidative Stress Inhibition via Sirtuin 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