Resveratrol protects human endothelium from H2O2-induced oxidative stress and senescence via SirT1 activation

Chung Lan Kao, Liang Kung Chen, Yuh Lih Chang, Ming Chih Yung, Chuan Chih Hsu, Yu Chih Chen, Wen Liang Lo, Shih Jen Chen, Hung Hai Ku, Shin Jang Hwang

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155 Citations (Scopus)

Abstract

Aim: Silencing information regulator (SirT1), a NAD-dependent histone deacetylase, is an essential media- tor of longevity in normal cells by calorie restriction. SirT1 has many biological functions, including tran- scription regulation, cell differentiation inhibition, cell cycle regulation, and anti-apoptosis. Resveratrol (RV)- induced SirT1 activation also improves endothelial dysfunction and suppresses vascular inflammation. In this study, we investigated the roles of RV-induced SirT1 activation in endothelial cells under oxidative stress. Methods: SirT1 mRNA expression levels were examined in the endothelium layer (endothelial cells) of cardi- ac coronary vessels from patients receiving coronary artery bypass graft surgery (CABG) surgery and aged rats using reverse transcriptase polymerase chain reaction (RT-PCR). To further explore the effect of SirT1 activa- tion on oxidative stress-induced aging, senescence-associated β-galactosidase (SA-β-gal) expression in RV- treated human umbilical vein endothelial cells (HUVECs) with or without H2O2 treatment was evaluated. Results: SirT1 expression was decreased in aged and atherosclerotic vessels in vivo, and significantly reduced in endothelial cells purified from vessel tissues. Furthermore, SirT1 levels were dose-depend- ently increased in RV-treated HUVECs. The SA-β gal assay showed that RV inhibited the senescent phenotype of H2O2-treated HUVECs. Reactive oxygen species (ROS) production and the percentage of cells positive for SA-β gal were significantly increased in siRNA-SirT1 (knockdown of SirT1 expression)-treated HUVEC cells. Importantly, the treatment effect of RV was significantly abolished in the oxidative effects of H2O2-treated HUVECs by siRNA-SirT1. Conclusion: Our data suggested that SirT1 could be a crucial factor involved in the endothelial cells of atherosclerotic CAGB patients and aging rats. RV is a potential candidate for preventing oxidative stress-induced aging in endothelial cells. RV may also prevent ROS-induced damage via increased endothelial SirT1 expression.

Original languageEnglish
Pages (from-to)970-979
Number of pages10
JournalJournal of Atherosclerosis and Thrombosis
Volume17
Issue number9
Publication statusPublished - 2010
Externally publishedYes

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Keywords

  • Cardiovascular dysfunction
  • Human umbilical vein endothelial cells
  • NAD-dependent histone deacetylase
  • Resveratrol
  • SirT1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Internal Medicine
  • Biochemistry, medical

Cite this

Kao, C. L., Chen, L. K., Chang, Y. L., Yung, M. C., Hsu, C. C., Chen, Y. C., Lo, W. L., Chen, S. J., Ku, H. H., & Hwang, S. J. (2010). Resveratrol protects human endothelium from H2O2-induced oxidative stress and senescence via SirT1 activation. Journal of Atherosclerosis and Thrombosis, 17(9), 970-979.