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5-Hydroxydecanoate Abolishes Cardioprotective Effects of a Structural Analogue of Apelin-12 in Ischemia/Reperfusion Injury

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Abstract

Chemically modified peptide apelin-12 (MA) with enhanced resistance to degradation by proteolytic enzymes is able to protect the heart against myocardial ischemia and reperfusion. This study was aimed to explore the role of mitochondrial ATP-sensitive K+-channels (mitoKATP) in effects of MA on myocardial energy state and membrane integrity in ischemia/reperfusion (I/R) injury. Isolated perfused working rat hearts were used to simulate global ischemia and reperfusion. Acute myocardial infarction was induced by coronary artery occlusion followed by restoration of coronary blood flow in anesthetized rats. Myocardial infarct size and cardiac dysfunction were used as indices of I/R injury at the end of reperfusion. Co-infusion of 5-hydroxydecanoate (5HD), the mitoKATP blocker, along with MA before ischemia significantly decreased functional recovery of isolated hearts as compared to administration of MA alone. These effects were accompanied by increased LDH release in the myocardial effluent, reduced restoration of myocardial ATP, AN, Cr, adenylate energy charge (AEC), and lactate accumulation. Coadministration of 5HD and MA at the onset of reperfusion substantially reduced infarct-limiting effect of the peptide in rats in vivo and increased the plasma LDH and CK-MB activity compared with MA treatment. Additionally, 5HD abolished MA influence on the metabolic state of the area at risk (AAR) at the end of reperfusion. In this case, the contents of metabolites and AEC in the AAR did not differ significantly from the values in control. Therefore, restoration of myocardial energy metabolism and sarcolemma integrity via activation of mitoKATP may be of critical importance for MA-induced protection against I/R injury.

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Acknowledgements

This work was supported by the Russian Foundation for Basic Research (Grant No. 14-04-00012a). The authors are grateful to Dr. M.V. Sidorova for synthesis of peptide MA and discussion of the results.

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Authors and Affiliations

  1. Russian Cardiology Research and Production Complex, Moscow, Russian Federation

    Oleg Pisarenko, Valentine Shulzhenko, Irina Studneva, Larisa Serebryakova & Oksana Veselova

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  1. Oleg Pisarenko
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  2. Valentine Shulzhenko
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  3. Irina Studneva
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  4. Larisa Serebryakova
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  5. Oksana Veselova
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Correspondence to Oleg Pisarenko.

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The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving animals were in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and other Scientific Purposes (No 123 of 18 March 1986).

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Pisarenko, O., Shulzhenko, V., Studneva, I. et al. 5-Hydroxydecanoate Abolishes Cardioprotective Effects of a Structural Analogue of Apelin-12 in Ischemia/Reperfusion Injury. Int J Pept Res Ther 23, 333–341 (2017). https://doi.org/10.1007/s10989-016-9565-1

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  • DOI: https://doi.org/10.1007/s10989-016-9565-1

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