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Apelin reduces myocardial reperfusion injury independent of PI3K/Akt and P70S6K [Abstract]

Kleinz, M. J. and Baxter, Gary Francis 2007. Apelin reduces myocardial reperfusion injury independent of PI3K/Akt and P70S6K [Abstract]. Journal of Molecular and Cellular Cardiology 42 (6, S1) , S203. 10.1016/j.yjmcc.2007.03.616

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Abstract

Apelin peptides are endogenous ligands of the apelin receptor (APJ) and are expressed in endothelial cells and adipocytes. Apelins regulate vascular tone, cardiac contractility and have been reported to protect from isoprenaline-induced myocardial injury. Furthermore, apelin peptides activate components of the reperfusion injury salvage kinase (RISK) pathway such as PI3K/Akt and P70S6 kinase (P70S6K) in transgenic cell based assays. We therefore hypothesised that apelin peptides may protect the post-ischaemic myocardium from reperfusion injury via activation of the RISK pathway and tested this hypothesis in a rat isolated heart model of ischaemia and reperfusion. Hearts from anaesthetised male Sprague–Dawley rats (290–350 g) were excised and retrogradely perfused via the ascending aorta with oxygenated Krebs' buffer at 37 °C. After 20 min of equilibration the coronary artery was occluded for 35 min, followed by 120 min of reperfusion. Ischaemic risk zone and infarct size were determined by Evans' blue/triphenyltetrazolium staining and infarct size expressed as % risk zone. Pyr1-apelin-13 (pa13, 10−8M) was administered for 20 min starting 5 min before onset of reperfusion in the absence or presence of wortmannin (10−7M) and rapamycin (10−9M). Pa13 reduced infarct size by 22% compared to controls. This effect was maintained in the presence of the PI3K/Akt inhibitor wortmannin and P70S6K inhibitor rapamycin. Our results indicate that in line with expression of APJ receptors on cardiac myocytes, pa13 reduces reperfusion injury in the post-ischaemic heart. Wortmannin and rapamycin did not abolish apelin cardioprotection, suggesting involvement of alternative pathways in native heart tissues.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Uncontrolled Keywords: Apelin; Reperfusion injury; Cardioprotection
Additional Information: 19th World Congress of the ISHR, Bologna, ITaly 2007
Publisher: Elsevier
ISSN: 0022-2828
Last Modified: 04 Jun 2017 01:57
URI: http://orca-mwe.cf.ac.uk/id/eprint/6601

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