Objective: Autophagy is a cellular process by which damaged components are removed. Although autophagy can result in cell death, when optimally regulated, it might be cardioprotective. Resveratrol is a naturally occurring polyphenol also believed to be cardioprotective. Using a clinically relevant swine model of metabolic syndrome, we investigated the effects of resveratrol on autophagy in the chronically ischemic myocardium.
Methods: Yorkshire swine were fed a regular diet (n = 7), a high cholesterol diet (n = 7), or a high cholesterol diet with supplemental resveratrol (n = 6). After 4 weeks, an ameroid constrictor was surgically placed on the left circumflex artery to induce chronic myocardial ischemia. The diets were continued another 7 weeks, and then the ischemic and nonischemic myocardium were harvested for protein analysis.
Results: In the ischemic myocardium, a high cholesterol diet partly attenuated the autophagy, as determined by an increase in phosphorylated mammalian target of rapamycin (p-mTOR) and a decrease in p70 S6 kinase (P70S6K), lysosome-associated membrane protein (LAMP)-2, and autophagy-related gene 12-5 conjugate (ATG 12-5; P < .05). The addition of resveratrol blunted many of these changes, because the p-mTOR, P70S6K, and LAMP-2 levels were not significantly altered from those of the pigs fed a regular diet. Other autophagy markers were increased with a high cholesterol diet, including light chain 3A-II and beclin 1 (P < .05). In the nonischemic myocardium, beclin 1 was decreased in the high cholesterol-fed pigs (P < .05); otherwise no significant changes in protein expression were noted among the 3 groups.
Conclusions: In the chronically ischemic myocardium, resveratrol partly reversed the effects of a high cholesterol diet on autophagy. This might be a mechanism by which resveratrol exerts its cardioprotective effects.
Keywords: 23; 29; 31.2; 38.2; ACC; ATG 12-5; HCC; HCRV; LAMP; LC3; P70S6K; autophagy-related-gene 12-5 conjugate; high cholesterol control; high cholesterol plus resveratrol; light chain 3; lysosome-associated membrane protein; mTOR; mammalian target of rapamycin; p-mTOR; p70 S6 kinase; phosphorylated mTOR; regular diet control.
Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.