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The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury.

Ong, SB; Samangouei, P; Kalkhoran, SB; Hausenloy, DJ; (2015) The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury. Journal of Molecular and Cellular Cardiology , 78C 23 - 34. 10.1016/j.yjmcc.2014.11.005. Green open access

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Abstract

Ischemic heart disease (IHD) remains the leading cause of death and disability worldwide. For patients presenting with an acute myocardial infarction, the most effective treatment for limiting myocardial infarct (MI) size is timely reperfusion. However, in addition to the injury incurred during acute myocardial ischemia, the process of reperfusion can itself induce myocardial injury and cardiomyocyte death, termed 'myocardial reperfusion injury', the combination of which can be referred to as acute ischemia-reperfusion injury (IRI). Crucially, there is currently no effective therapy for preventing this form of injury, and novel cardioprotective therapies are therefore required to protect the heart against acute IRI in order to limit MI size and preserve cardiac function. The opening of the mitochondrial permeability transition pore (MPTP) in the first few minutes of reperfusion is known to be a critical determinant of IRI, contributing up to 50% of the final MI size. Importantly, preventing its opening at this time using MPTP inhibitors, such as cyclosporin-A, has been reported in experimental and clinical studies to reduce MI size and preserve cardiac function. However, more specific and novel MPTP inhibitors are required to translate MPTP inhibition as a cardioprotective strategy into clinical practice. In this article, we review the role of the MPTP as a mediator of acute myocardial IRI and as a therapeutic target for cardioprotection. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".

Type: Article
Title: The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.yjmcc.2014.11.005
Publisher version: http://dx.doi.org/10.1016/j.yjmcc.2014.11.005
Language: English
Additional information: © Elsevier 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. Access may be initially be restricted by the publisher.
Keywords: Cardioprotection, Ischemic heart disease, Mitochondrial permeability transition pore, Myocardial infarction, Myocardial ischemia–reperfusion injury
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/1459721
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