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Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemiareperfusion injury

Simpkin, JC; Yellon, DM; Davidson, SM; Lim, SY; Wynne, AM; Smith, CCT; (2007) Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemiareperfusion injury. Basic Research in Cardiology , 102 (6) pp. 518-528. 10.1007/s00395-007-0671-2.

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Abstract

Protection against myocardial ischemia-reperfusion (I/R) injury involves activation of phosphatidylinositol-3-OH kinase (PI3K)-Akt/protein kinase B and p44/42 mitogen-activated protein kinase (MAPK), components of the reperfusion injury salvage kinase (RISK) pathway. The adipocytokine, apelin, activates PI3K-Akt and p44/42 in various tissues and we, therefore, hypothesised that it might demonstrate cardioprotective activity. Employing both in vivo (open-chest) and in vitro (Langendorff and cardiomyocytes) rodent (mouse and rat) models ofmyocardial I/R injury we investigated if apelin administered at reperfusion at concentrations akin to pharmacological doses possesses cardioprotective activity. Apelin-13 and the physiologically less potent peptide, apelin-36, decreased infarct size in vitro by 39.6% (p < 0.01) and 26.1% (p < 0.05) respectively. In vivo apelin-13 and apelin-36 reduced infarct size by 43.1% (p < 0.01) and 32.7% (p < 0.05). LY294002 and UO126, inhibitors of PI3K-Akt and p44/42 phosphorylation respectively, abolished the protective effects of apelin-13 in vitro. Western blot analysis provided further evidence for the involvement of PI3K-Akt and p44/42 in the cardioprotective actions of apelin. In addition,mitochondrial permeability transition pore (MPTP) opening was delayed by both apelin-13 (127%, p < 0.01) and apelin-36 (93%, p < 0.01) which, in the case of apelin-13, was inhibited by LY294002 and mitogen-activated protein kinase kinase (MEK) inhibitor 1. This is the first study to yield evidence that the adipocytokine, apelin, produces direct cardioprotective actions involving the RISK pathway and the MPTP. © Steinkopff-Verlag 2007.

Type: Article
Title: Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemiareperfusion injury
DOI: 10.1007/s00395-007-0671-2
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/10029776
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