Uncouple my heart: the benefits of inefficiency.
Myocardial ischemia/reperfusion (IR) injury leads to structural changes in the heart muscle later followed by functional decline due to progressive fibrous replacement. Hence approaches to minimize IR injury are devised, including ischemic pre-and postconditioning. Mild uncoupling of oxidative phosphorylation is one of the mechanisms suggested to be cardioprotective as chemical uncoupling mimics ischemic preconditioning. Uncoupling protein 2 is proposed to be the physiological counterpart of chemical uncouplers and is thought to be a part of the protective machinery of cardiomyocytes. Morphological changes in the mitochondrial network likely accompany the uncoupling with mitochondrial fission dampening the signals leading to cardiomyocyte death. Here we review recent data on the role of uncoupling in cardioprotection and propose that low concentrations of dietary polyphenols may elicit the same cardioprotective effect as dinitrophenol and FCCP, perhaps accounting for the famed "French paradox".
Institute of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hnevotinska 3, 775 15, Olomouc, Czech Republic. martin.modriansky@upol.cz
Martin
M
Modrianský
Eva
E
Gabrielová
D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D004140:Dinitrophenols / Q000627:therapeutic use; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D024101:Mitochondrial Proteins / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D010636:Phenols / Q000627:therapeutic use; D059808:Polyphenols; D015398:Signal Transduction / Q000187:drug effects; D014475:Uncoupling Agents / Q000627:therapeutic use*; D000071246:Uncoupling Protein 2
D002316:Cardiotonic Agents; D004140:Dinitrophenols; D005419:Flavonoids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D010636:Phenols; D059808:Polyphenols; C000604389:UCP2 protein, human; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone