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.
- Cardiovascular dysfunction
- Human umbilical vein endothelial cells
- NAD-dependent histone deacetylase
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Biochemistry, medical
- Internal Medicine