Abstract 323: Resveratrol Attenuates Pressure Overload-induced Heart Failure

Abstract

The purpose of this study was to determine whether the potent antioxidant, resveratrol, attenuates the adverse cardiac remodeling and dysfunction in pressure overload heart failure induced by transverse aortic constriction (TAC). Male C57BL6 mice (26-28 g) were subjected to either sham or TAC surgery. One group of TAC mice was given daily resveratrol treatment (oral gavage, 100 mg/kg/body weight (bw) for 28 days starting on day 2 after surgery. Echocardiographic, biometric, and immunohistological analyses were performed on the three groups of mice. All echocardiographic parameters examined (internal diameters, fractional shortening , and ejection fraction) demonstrated significantly greater adverse cardiac remodeling and dysfunction in the TAC compared to the sham mice. These pathological changes were significantly improved by resveratrol treatment. At day 28 fractional shortening was 46.5±2.4%, 26.2±2.0%, and 35±2.6% in the sham, TAC, and TAC + resveratrol mice, respectively. This was reflected by lung weight/bw ratios of 4.2±0.3 mg/g (sham), 8.6±0.9 mg/g (TAC) and 7.2±0.4 mg/g (TAC + resveratrol). Resveratrol treatment also significantly reduced cardiac hypertrophy as determined by the heart weight/bw ratios (sham, 4.8±0.3 mg/g; TAC, 8.7±0.6 mg/g; and TAC + resveratrol, 7.2±0.3 mg/g). Likewise, the TAC protocol significantly increased fibrosis (10.0±1.1%), compared to the sham-operated mice (0.7±0.3%), which was attenuated by resveratrol treatment (3.0±0.5%). Similar results were obtained when cardiomyocyte apoptosis was assessed. Both superoxide dismutase 2 and hypoxia inducible factor 1α were markedly increased in the TAC compared to the sham-operated mice most likely as a compensatory response to increased oxidative stress and hypoxia. These TAC-induced factors were significantly decreased by resveratrol treatment indicating that the resveratrol was acting in place of these stress inducible factors. In summary, these results demonstrate that resveratrol treatment significantly attenuates the adverse cardiac remodeling and dysfunction produced by the TAC protocol in C57/BL6 mice and that this activity is mediated, at least in part, by the inhibition of oxidative stress and hypoxia.