Activation of SIRT1 by Resveratrol Alleviates Pressure Overload-Induced Cardiac Hypertrophy via Suppression of TGF-beta 1 Signaling

Chen, Yong1,2,3; He, Ting4,5; Zhang, Zhongjun4,6; Zhang, Junzhi4,6

2021

10.1159/000518464

PHARMACOLOGY   影响因子和分区

0031-7012

1423-0313

Introduction: Silent information regulator 1 (SIRT1) has been extensively investigated in the cardiovascular system and has been shown to play a pivotal role in mediating cell death/survival, energy production, and oxidative stress. However, the functional role of SIRT1 in pressure overload-induced cardiac hypertrophy and dysfunction remains unclear. Resveratrol (Rsv), a widely used activator of SIRT1, has been reported to protect against cardiovascular disease. We here examine whether activation of SIRT1 by Rsv attenuate pressure overload-induced cardiac hypertrophy and to identify the underlying molecular mechanisms. Methods: In vivo, rat model of pressure overload-induced myocardial hypertrophy was established by abdominal aorta constriction (AAC) procedure. In vitro, Angiotensin II (Ang II) was applied to induce hypertrophy in cultured neonatal rat cardiomyocytes (NCMs). Hemodynamics and histological analyses of the heart were evaluated. The expression of SIRT1, transforming growth factor-beta 1 (TGF-beta 1)/phosphorylated (p)-small mother against decapentaplegic (Smad)3 and hypertrophic markers were determined by immunofluorescence, real-time PCR, and Western blotting techniques. Results: In the current study, Rsv treatment improved left ventricular function and reduced left ventricular hypertrophy and cardiac fibrosis significantly in the pressure overload rats. The expression of SIRT1 was significantly reduced, while the expression of TGF-beta 1/p-Smad3 was significantly enhanced in AAC afflicted rat heart. Strikingly, treatment with Rsv restored the expressions of SIRT1 and TGF-beta 1/p-Smad3 under AAC influence. However, SIRT1 inhibitor Sirtinol (Snl) markedly prevented the effects of Rsv, which suggest that SIRT1 signaling pathway was involved in the cardiac protective effect of Rsv. In vitro studies performed in Ang II-induced hypertrophy in NCMs confirmed the cardiac protective effect of Rsv. Furthermore, the study presented that SIRT1 negatively correlated with the cardiac hypertrophy, cardiac fibrosis, and the TGF-beta 1/p-Smad3 expression. Conclusions: Taken together, these results indicated that activation of SIRT1 by Rsv atten-uates cardiac hypertrophy, cardiac fibrosis, and improves cardiac function possibly via regulation of the TGF-beta 1/p-Smad3 signaling pathway. Our study may provide a potential therapeutic strategy for cardiac hypertrophy. (C) 2021 S. Karger AG, Basel

Resveratrol Cardiac hypertrophy Pressure overload Silent information regulator 1 Transforming growth factor-1 beta

SCI

英语

通讯

Hubei Provincial Science and Technology Research Project (Department of Education) of China[Q20161109] ; National Natural Science Foundation of China[81700435] ; Shenzhen Key Medical Discipline Construction Fund[SZXK044] ; Sanming Project of Medicine in Shenzhen[SZSM202011021]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:000847918400010

KARGER

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Shenzhen Univ, Dept Neurosurg, Gen Hosp, Shenzhen, Peoples R China
2.Shenzhen Univ, Dept Neurosurg, Clin Med Acad, Shenzhen, Peoples R China
3.Wuhan Univ Sci & Technol, Tianyou Hosp, Dept Neurosurg, Wuhan, Peoples R China
4.Jinan Univ, Clin Med Coll 2, Dept Anesthesiol, Shenzhen Peoples Hosp, Shenzhen, Peoples R China
5.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Re, Guangzhou, Peoples R China
6.Southern Univ Sci & Technol, Dept Anesthesiol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Shenzhen, Peoples R China

Chen, Yong,He, Ting,Zhang, Zhongjun,et al. Activation of SIRT1 by Resveratrol Alleviates Pressure Overload-Induced Cardiac Hypertrophy via Suppression of TGF-beta 1 Signaling[J]. PHARMACOLOGY,2021,106(11-12).

Chen, Yong,He, Ting,Zhang, Zhongjun,&Zhang, Junzhi.(2021).Activation of SIRT1 by Resveratrol Alleviates Pressure Overload-Induced Cardiac Hypertrophy via Suppression of TGF-beta 1 Signaling.PHARMACOLOGY,106(11-12).

Chen, Yong,et al."Activation of SIRT1 by Resveratrol Alleviates Pressure Overload-Induced Cardiac Hypertrophy via Suppression of TGF-beta 1 Signaling".PHARMACOLOGY 106.11-12(2021).