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

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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.

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Authors and Affiliations

  1. The Hatter Cardiovascular Institute, University College London Hospital and Medical School, 67 Chenies Mews, London, WC1E 6HX, UK

    J. C. Simpkin,  D. M. Yellon, S. M. Davidson, S. Y. Lim, A. M. Wynne & C. C. T. Smith

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  1. J. C. Simpkin
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  2. D. M. Yellon
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  3. S. M. Davidson
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  4. S. Y. Lim
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Correspondence to D. M. Yellon.

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Simpkin, J.C., Yellon, D.M., Davidson, S.M. et al. Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemiareperfusion injury. Basic Res Cardiol 102, 518–528 (2007). https://doi.org/10.1007/s00395-007-0671-2

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  • DOI: https://doi.org/10.1007/s00395-007-0671-2

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