title: Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-β/Smad3 pathway.
abstract: Sirtuins [sirtuin (SIRT)1-SIRT7] mediate the longevity-promoting effects of calorie restriction in yeast, worms, flies, and mice. Additionally, SIRT3 is the only SIRT analog whose increased expression has been shown to be associated with longevity in humans. The polyphenol resveratrol (RSV) is the first compound discovered able to mimic calorie restriction by stimulating SIRTs. In the present study, we report that RSV activated SIRT3 in cardiac fibroblasts both in vivo and in vitro. Moreover, in wild-type mice, RSV prevented cardiac hypertrophy in response to hypertrophic stimuli. However, this protective effect was not observed in SIRT3 knockout mice. Additionally, the activation of SIRT3 by RSV ameliorated collagen deposition and improved cardiac function. In isolated cardiac fibroblasts, pretreatment with RSV suppressed fibroblast-to-myoblast transformation by inhibiting the transforming growth factor-β/Smad3 pathway. Therefore, these data indicate that the activation of SIRT3 by RSV could ameliorate cardiac fibrosis and improve cardiac function via the transforming growth factor-β/Smad3 pathway.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, Shandong, China; and Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Tongshuai
authors.initials: T
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, Shandong, China; and Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Junni
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, Shandong, China; and Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, Shandong, China; and Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Shujian
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, Shandong, China; and Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, Shandong, China; and Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, Shandong, China; and Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, Shandong, China; and Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China bupeili@gmail.com.cn.
authors.forename: Peili
authors.initials: P
authors.lastname: Bu
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism; D000077185:Resveratrol; D056566:Sirtuin 3 / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C525046:Sirt3 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D013267:Stilbenes; D016212:Transforming Growth Factor beta; D003094:Collagen; D056566:Sirtuin 3; D000077185:Resveratrol
keywords: cardiac function; fibrosis; mothers against decapentaplegic homolog 3; resveratrol; sirtuin 3; transforming growth factor-β