Resveratrol protects against diet-induced atherosclerosis by reducing low-density lipoprotein cholesterol and inhibiting inflammation in apolipoprotein E-deficient mice.

Abstract

Resveratrol (RES) is a polyphenol compound that has been shown a promising cardioprotective effect. However, some reports have yielded conflicting findings. Herein, we investigated the anti-atherosclerotic effects of RES in apolipoprotein E (apo E)-deficient mice on a high cholesterol diet. Firstly, atherosclerosis was induced by feeding a high cholesterol diet to apo E-deficient mice. Then, we examined its effects on weight control, and serum interleukin-6 (IL-6) levels and used histopathological methods to analyze morphology and inflammatory marker of atherosclerotic lesions in mice orally supplemented with high (25 mg/kg/day) and low (5 mg/kg/day) doses of RES for 8 weeks. Mice with high dose of RES had reduced epididymal fat pads, and lower serum IL-6 levels compared with those of control mice. Moreover, RES in high doses also decreased the low-density lipoprotein cholesterol (LDL-C) levels and atherogenic index (LDL-C/HDL-C) in the mice. Dissection of high-dose RES-treated mice revealed a marked reduction in fat deposition, percentage of mice with atherosclerotic lesion, and intima/media ratio in the aortic areas. The expressions of macrophage-specific marker F4/80 and cardiovascular inflammatory marker NF-κB in atherosclerotic vessels were both diminished in the atherosclerotic vessels of high-dose RES-supplementated apo E-deficient mice. These results suggest that RES prevented the effects of a high cholesterol diet on the rate of accretion in atherosclerosis progression by reducing the LDL-C levels and suppressing atherosclerotic inflammation. RES can therefore be valuable in the development of new anti-atherosclerotic agents.