title: Resveratrol regulates autophagy signaling in chronically ischemic myocardium.
abstract: 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.
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI.
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Sabe
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI.
authors.forename: Nassrene Y
authors.initials: NY
authors.lastname: Elmadhun
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Dalal
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Robich
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Brown University Warren Alpert School of Medicine, Providence, RI. Electronic address: fsellke@lifespan.org.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D000077185:Resveratrol; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D013552:Swine; D013556:Swine, Miniature; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D002791:Cholesterol, Dietary; D052119:Lysosomal-Associated Membrane Protein 2; D008869:Microtubule-Associated Proteins; D013267:Stilbenes; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D000077185:Resveratrol
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