Protective effect of resveratrol against pressure overload‐induced heart failure

Abstract

Transverse aortic constriction (TAC)-induced pressure overload (PO) causes adverse cardiac remodeling and dysfunction that progresses to heart failure (HF). The purpose of this study was to determine whether the potent antioxidant, resveratrol, significantly attenuates PO-induced HF in wild-type mice. Male C57BL6 mice were subjected to either sham or TAC surgery. One group of TAC mice was given daily resveratrol treatment. Echocardiographic, biometric, and immunohistological analyses were performed on the three groups of mice. All echocardiographic parameters demonstrated significantly greater adverse cardiac remodeling and dysfunction in the TAC compared to the sham mice. Increases in the ratios of heart weight (HW)/body weight (BW) and lung weight (LW)/BW and a sharp decline in the percentage of ejection fraction and fractional shortening were found in TAC relative to sham mice. Likewise, the TAC protocol increased markers of oxidative stress, cardiac hypertrophy, inflammation, fibrosis, hypoxia, and apoptosis. These pathological changes were significantly attenuated by resveratrol treatment. Resveratrol treatment significantly attenuates the adverse cardiac remodeling and dysfunction produced by the TAC protocol in C57/BL6 mice and this activity is mediated, at least in part, by the inhibition of oxidative stress and inflammation indicating a therapeutic potential of resveratrol in HF.

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

“…In the TO-2 hamster heart, resveratrol enhanced cardiac SOD2 expression in a SIRT1-dependent manner and reduced ROS [212]. Similarly, SOD2 activity and levels of the ROS scavenger, glutathione, were increased by resveratrol in TAC mice when compared to TAC mice treated with vehicle [209]. On the other hand, in an MI model of cardiac hypertrophy, the expression level of SOD2 was unaltered by resveratrol [171], suggesting that SOD2 up-regulation may not be the main anti-oxidant mechanism of resveratrol.…”

“…For instance, in the SHR, low doses of resveratrol (2.5 mg/kg/day) prevented cardiac hypertrophy without reducing BP [30,32]. Furthermore, resveratrol reduced cardiac hypertrophy in surgical models of increased afterload [208][209][210], which are mechanically confined to elevated afterloads. Additionally, resveratrol has been shown to prevent/treat heart failure in models where elevated afterload is not the cause of hypertrophy, such as in the TO-2 hamster model of heart failure [212], in the experimental model of autoimmune myocarditis [211], in a number of rodent models of infarction [158,[167][168][169]171], and in isolated cardiomyocytes [216].…”

“…However, in an aortic-banded pressure-overload model of hypertension, resveratrol (2.5 mg/kg/day) treatment prevented both cardiac hypertrophy and cardiac dysfunction [210]. Recently, Gupta et al used transverse aortic constriction (TAC)-induced pressure-overload model of cardiac hypertrophy in mice to study the effects of resveratrol [209]. In that study, mice receiving 10 mg/kg/day resveratrol following the TAC surgery displayed significantly reduced pathological cardiac remodelling and dysfunction as well as reduced oxidative stress, inflammation, fibrosis and apoptosis [209].…”

“…Recently, Gupta et al used transverse aortic constriction (TAC)-induced pressure-overload model of cardiac hypertrophy in mice to study the effects of resveratrol [209]. In that study, mice receiving 10 mg/kg/day resveratrol following the TAC surgery displayed significantly reduced pathological cardiac remodelling and dysfunction as well as reduced oxidative stress, inflammation, fibrosis and apoptosis [209]. Moreover, resveratrol treatment in an aortic-banded pressure-overload model of cardiac hypertrophy in rats prevented and reversed hypertrophy [208,210].…”

“…Resveratrol has been investigated in a number of these models including pressure-overload [208][209][210], volume overload [210], SHRs [30,32], doxorubicin-induced cardiotoxicity [202,203] (see section on chemotherapy-induced cardiotoxicity), MI, ischemia-reperfusion injury [168,169,171], myocarditis [211], and a TO-2 hamster model of heart failure [212] (Table 4). Many studies using resveratrol in these models focus on the ability of resveratrol to prevent cardiac hypertrophy and/or prevent cardiac dysfunction leading to heart failure as opposed to testing resveratrol as a heart failure treatment per se.…”