title: The mitochondrial permeability transition pore as a target for preconditioning and postconditioning.
abstract: The experimental evidence supporting the mitochondrial permeability transition pore (mPTP) as a major mediator of lethal myocardial reperfusion injury and therefore a critical target for cardioprotection is persuasive. Although, its molecular identity eludes investigators, it is generally accepted that mitochondrial cyclophilin-D, the target for the inhibitory effects of cyclosporine-A on the mPTP, is a regulatory component of the mPTP. Animal myocardial infarction studies and a recent clinical proof-of-concept study have demonstrated that pharmacologically inhibiting its opening at the onset of myocardial reperfusion reduces myocardial infarct size in the region of 30-50%. Interestingly, the inhibition of mPTP opening at this time appears to underpin the infarct-limiting effects of the endogenous cardioprotective strategies of ischemic preconditioning (IPC) and postconditioning (IPost). However, the mechanism underlying this inhibitory action of IPC and IPost on mPTP opening is unclear. The objectve of this review article will be to explore the potential mechanisms which link IPC and IPost to mPTP inhibition in the reperfused heart.
authors.affiliation: The Hatter Institute and Center for Cardiology, University College London Hospitals and Medical School, Grafton Way, London, UK. d.hausenloy@ucl.ac.uk
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
authors.forename: Sang-Bing
authors.initials: SB
authors.lastname: Ong
authors.forename: Derek M
authors.initials: DM
authors.lastname: Yellon
mesh_terms: D000818:Animals; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore