- 作者：Ashraf A. Sabe ; Nassrene Y. Elmadhun ; Rahul S. Dalal ; Michael P. Robich ; Frank W. Sellke
- 关键词：23 ; 29 ; 31.2 ; 38.2
- 刊名：The Journal of Thoracic and Cardiovascular Surgery
- 出版年：February, 2014
- 年：2014
- 卷：147
- 期：2
- 页码：792-799
- 全文大小：637 K
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聽=聽7), a high cholesterol diet (n聽=聽7), or a high cholesterol diet with supplemental resveratrol (n聽=聽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聽<聽.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聽autophagy markers were increased with a high cholesterol diet, including light chain 3A-II and beclin 1 (P聽<聽.05). In the nonischemic myocardium, beclin 1 was decreased in the high cholesterol-fed pigs (P聽<聽.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.