Abstract 5326: SIRT1-Dependent and -Independent Effects of Resveratrol on Cardiovascular Oxidative Stress

SIRT1 is a NAD+-dependent class III histone deacetylase. Recent studies point to SIRT1 as a key regulator of angiogenesis, vascular tone and endothelial function. The aim of the present study was to investigate the role of SIRT1 in regulating oxidative stress in the cardiovascular system. Atherosclerotic apolipoprotein E knockout (ApoE-KO) mice were treated with a SIRT1 activator, resveratrol (30 or 100 mg/kg/day for 7 days via gavage). Resveratrol treatment significantly reduced the levels of 3-nitrotyrosine, malondialdehyde and superoxide in the heart, which was associated with an upregulation of superoxide dismutase isoforms (SOD1–3), glutathione peroxidase 1 (GPx1), and catalase. In parallel, mRNA expression of NADPH oxidase subunits NOX2 and NOX4 was reduced. Resveratrol also inhibited the translocation of p47phox and Rac1 and decreased the activity of NADPH oxidase complex in heart membrane fraction. The cofactor of endothelial nitric oxide synthase (eNOS), (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4),...