title: The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury.
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".
authors.affiliation: Hatter Cardiovascular Institute, Institute of Cardiovascular Science, NIHR University College London Hospitals Biomedical Research Centre, University College London Hospital & Medical School, 67 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Sang-Bing
authors.initials: SB
authors.lastname: Ong
authors.affiliation: Hatter Cardiovascular Institute, Institute of Cardiovascular Science, NIHR University College London Hospitals Biomedical Research Centre, University College London Hospital & Medical School, 67 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Parisa
authors.initials: P
authors.lastname: Samangouei
authors.affiliation: Hatter Cardiovascular Institute, Institute of Cardiovascular Science, NIHR University College London Hospitals Biomedical Research Centre, University College London Hospital & Medical School, 67 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Siavash Beikoghli
authors.initials: SB
authors.lastname: Kalkhoran
authors.affiliation: Hatter Cardiovascular Institute, Institute of Cardiovascular Science, NIHR University College London Hospitals Biomedical Research Centre, University College London Hospital & Medical School, 67 Chenies Mews, London WC1E 6HX, UK; Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore. Electronic address: d.hausenloy@ucl.ac.uk.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D058990:Molecular Targeted Therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D020928:Mitogen-Activated Protein Kinases
keywords: Cardioprotection; Ischemic heart disease; Mitochondrial permeability transition pore; Myocardial infarction; Myocardial ischemia–reperfusion injury