Resveratrol regulates autophagy signaling in chronically ischemic myocardium.


Journal Article

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.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.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.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.

Full Text

Cited Authors

  • Sabe, AA; Elmadhun, NY; Dalal, RS; Robich, MP; Sellke, FW

Published Date

  • February 2014

Published In

Volume / Issue

  • 147 / 2

Start / End Page

  • 792 - 798

PubMed ID

  • 24267781

Pubmed Central ID

  • 24267781

Electronic International Standard Serial Number (EISSN)

  • 1097-685X

International Standard Serial Number (ISSN)

  • 0022-5223

Digital Object Identifier (DOI)

  • 10.1016/j.jtcvs.2013.06.062


  • eng