eprintid: 1459721 rev_number: 37 eprint_status: archive userid: 608 dir: disk0/01/45/97/21 datestamp: 2015-01-02 11:55:32 lastmod: 2021-12-06 00:27:17 status_changed: 2015-11-09 15:39:20 type: article metadata_visibility: show item_issues_count: 0 creators_name: Ong, SB creators_name: Samangouei, P creators_name: Kalkhoran, SB creators_name: Hausenloy, DJ title: The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury. ispublished: pub divisions: UCL divisions: B02 divisions: D14 divisions: GA2 keywords: Cardioprotection, Ischemic heart disease, Mitochondrial permeability transition pore, Myocardial infarction, Myocardial ischemia–reperfusion injury note: © 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. 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". date: 2015-01 official_url: http://dx.doi.org/10.1016/j.yjmcc.2014.11.005 vfaculties: VFPHS oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: REVIEW verified: verified_manual elements_source: PubMed elements_id: 1000879 doi: 10.1016/j.yjmcc.2014.11.005 pii: S0022-2828(14)00347-2 language_elements: ENG lyricists_name: Hausenloy, Derek lyricists_id: DHAUS05 full_text_status: public publication: Journal of Molecular and Cellular Cardiology volume: 78C pagerange: 23 - 34 citation: 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 <https://doi.org/10.1016/j.yjmcc.2014.11.005>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1459721/1/hausenloy_2014_JMCC_MPTP_review_revision_30102014.docx