Copyright © 2006, European Society of Cardiology
Survival kinases in ischemic preconditioning and postconditioning
The Hatter Institute and Centre for Cardiology, University College London Hospital, Chenies Mews, London, WC1E 6DB, United Kingdom
* Corresponding author. Tel.: +44 207 380 9776; fax: +44 207 388 5095. Email address: hatter-institute{at}ucl.ac.uk
Despite nearly twenty years of research into the field of ischemic preconditioning, the actual mechanism of protection remains unclear. However, much progress has been made in elucidating the signal transduction pathways that convey the extracellular signal initiated by the preconditioning stimulus to the intracellular targets of cardioprotection, with many of these pathways involving the activation of a diverse array of survival protein kinase cascades. The powerful protective benefits of ischemic preconditioning have not yet been realised in the clinical arena, not least because of the prerequisite for any preconditioning intervention to be applied prior to the onset of index ischemia, which in the case of an acute myocardial infarction is difficult to institute. In this regard, the newly described phenomenon of ischemic postconditioning, which comprises a cardioprotective intervention that can be applied at the time of myocardial reperfusion, offers a far more attractive and amenable approach to myocardial protection. Interestingly, certain survival protein kinase cascades recruited at the time of myocardial reperfusion appear to be shared by both ischemic preconditioning and postconditioning, thereby offering a potentially common target of cardioprotection. The often disputed roles these different protein kinases play in mediating the cardioprotective effects of ischemic preconditioning and postconditioning are reviewed in this article, and include protein kinases C, G, and A, members of the MAPK family (Erk1/2, p38, JNK and BMK1), the PI3K–Akt cascade, and the JAK-STAT pathway.
KEYWORDS Signalling; Preconditioning; Kinases
Time for primary review 19 days
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