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: Sang-Bing Ong, Parisa Samangouei, Siavash Beikoghli Kalkhoran, Derek J Hausenloy
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 78 Pg. 23-34 (Jan 2015) ISSN: 1095-8584 [Electronic] England
• PMID: 25446182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014. Published by Elsevier Ltd.

Chemical References

• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Biological Transport
• Humans
• Ischemic Preconditioning, Myocardial
• Mitochondria, Heart (drug effects, metabolism)
• Mitochondrial Membrane Transport Proteins (antagonists & inhibitors, metabolism)
• Mitochondrial Permeability Transition Pore
• Mitogen-Activated Protein Kinases (metabolism)
• Molecular Targeted Therapy
• Myocardial Reperfusion Injury (drug therapy, metabolism)
• Signal Transduction (drug effects)