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

Autor: V.S. Shulzhenko, Oleg I. Pisarenko, Oksana Veselova, L. I. Serebryakova, Irina Studneva
Rok vydání: 2016
Předmět:
Zdroj: International Journal of Peptide Research and Therapeutics. 23:333-341
ISSN: 1573-3904
1573-3149
DOI: 10.1007/s10989-016-9565-1
Popis: 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.
Databáze: OpenAIRE
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