The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning.
Novel treatment approaches, as potential adjunctive therapy to current reperfusion strategies (such as thrombolysis, primary coronary angioplasty, and cardiac surgery), are required to provide further cardioprotection in the setting of an acute myocardial infarction to effect further reductions in morbidity and mortality. In this regard, the activation of prosurvival kinases, such as Akt and Erk1/2 (which we have termed the reperfusion injury salvage kinase [RISK] pathway), at the time of reperfusion, has been demonstrated to confer powerful cardioprotection against myocardial ischemia-reperfusion injury. In this review, we present evidence suggesting that the cardioprotective phenomena of ischemic preconditioning and the recently described ischemic postconditioning exert their cardioprotective effects through the recruitment of the RISK pathway, at the time of reperfusion, and that the protection in these settings is mediated through the inhibition of mitochondrial permeability transition pore (mPTP) opening at this time. Therefore, the pharmacologic manipulation of the RISK pathway at the time of reperfusion may enable one to harness the powerful cardioprotective benefits of both ischemic preconditioning and postconditioning, and provide a novel approach to cardioprotection.
Hausenloy
Derek J
DJ
The Hatter Institute and Centre for Cardiology, University College London Hospital, WC1E 6DB London, UK.
Tsang
Andrew
A
Yellon
Derek M
DM
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects*; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors; D019157:Ischemic Preconditioning, Myocardial; D020935:MAP Kinase Signaling System; D008929:Mitochondria, Heart / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011494:Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3