title: Long-term oral resveratrol intake provides nutritional preconditioning against myocardial ischemia/reperfusion injury: involvement of VDAC1 downregulation.
abstract: METHODS
  This study elucidates the effects of long-term nutritional preconditioning by resveratrol on ischemia/reperfusion (I/R) injury and its underlying mechanisms.
  
  
  RESULTS
  Mice were treated with resveratrol at 2.0 mg/kg/day by gastric gavages for 6 wk. Then hearts were isolated and subjected to I/R injury in a Langendorff apparatus. Resveratrol significantly improved left ventricular pressure, ±dp/dtmax, and coronary flow; decreased the lactate dehydrogenase and creatine phosphokinase activities; and reduced the infarction size. Additionally, long-term oral resveratrol intake prevented mitochondrial permeability transition pore opening and subsequently inhibited mitochondria-mediated apoptosis, as demonstrated by decrease of cytochrome c release, inactivation of caspase-3, and reduction of terminal deoxynucleotidyl transferase mediated nick end labeling positive cells. Furthermore, resveratrol inhibited the upregulation of voltage-dependent anion channel 1 (VDAC1) expression induced by I/R injury. Local left-ventricle overexpression of VDAC1 by adenovirus diminished the protective effect of resveratrol against I/R injury, indicating that VDAC1 plays an important role in resveratrol-mediated cardioprotection.
  
  
  CONCLUSIONS
  Our data revealed that long-term oral intake of resveratrol sets nutritional preconditioning to cope with myocardial I/R injury. Strikingly, we found that resveratrol downregulates VDAC1, leading to prevention of mitochondrial permeability transition pore opening and cardiomyocyte apoptosis.
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, P. R. China; Department of Pharmacology & Molecular Therapeutics, Nanchang University School of Pharmaceutical Science, Nanchang, P. R. China.
authors.forename: Zhangping
authors.initials: Z
authors.lastname: Liao
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.forename: Dong
authors.initials: D
authors.lastname: Yin
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yin
authors.forename: Songqing
authors.initials: S
authors.lastname: Lai
authors.forename: Jianguo
authors.initials: J
authors.lastname: Yao
authors.forename: Ming
authors.initials: M
authors.lastname: He
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation; D006321:Heart / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D051379:Mice; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009924:Organ Culture Techniques; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013267:Stilbenes; C494763:Vdac1 protein, mouse; D045304:Cytochromes c; D050995:Voltage-Dependent Anion Channel 1; D053148:Caspase 3; D000077185:Resveratrol
keywords: Ischemia-reperfusion; Mitochondrial permeability transition pore; Nutritional preconditioning; Resveratrol; Voltage-dependent anion channel