Smith, CCT and Lim, SY and Wynne, AM and Sivaraman, V and Davidson, SM and Mocanu, MM and Hausenloy, DJ and Yellon, DM (2011) Failure of the Adipocytokine, Resistin, to Protect the Heart From Ischemia-Reperfusion Injury. J CARDIOVASC PHARM T , 16 (1) 63 - 71. 10.1177/1074248410382232.
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Experimental studies have linked the adipocytokines with acute cardioprotection. Whether the adipocytokine, resistin, confers protection is, however, debatable. In the current study, the actions of resistin, administered at reperfusion, were investigated in in vivo and in vitro rodent and in vitro human models of myocardial ischemia-reperfusion (I/R) injury. Resistin did not reduce infarct size in Langendorff-perfused rat hearts or murine hearts perfused in vivo. Resistin also did not protect human atrial muscle subjected to hypoxia-reoxygenation. Although cyclosporin A delayed mitochondrial permeability transition pore (MPTP) opening in murine cardiomyocytes, resistin was ineffective. Western blot analysis revealed that resistin treatment was associated with enhanced phosphorylation of Akt, at both the serine-473 (+51.9%, P = .01) and threonine-308 (+107%, P < .01) phosphorylation sites, although not to the extent seen with ischemic preconditioning (+132.5%, P - .002 and +389.1%, P < .01, respectively). We conclude that resistin administered at reperfusion at concentrations/doses equivalent to normal (upper end) and pathological serum levels does not protect against I/R injury or inhibit MPTP opening.
|Title:||Failure of the Adipocytokine, Resistin, to Protect the Heart From Ischemia-Reperfusion Injury|
|Keywords:||resistin, cardioprotection, ischemia-reperfusion injury, RISK pathway, PERMEABILITY TRANSITION PORE, HUMAN ENDOTHELIAL-CELLS, HUMAN ATRIAL MUSCLE, INSULIN-RESISTANCE, UP-REGULATION, IN-VITRO, OBESITY, ADIPONECTIN, ACTIVATION, HORMONE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Cardiovascular Medicine|
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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