Reperfusion injury salvage kinase and survivor activating factor enhancement prosurvival signaling pathways in ischemic postconditioning: two sides of the same coin.
The discovery of ischemic postconditioning (IPost) has rejuvenated the field of cardioprotection. As an interventional strategy to be applied at the onset of myocardial reperfusion, the transition of IPost from a bench-side curiosity to potential clinical therapy has been impressively rapid. Its existence also confirms the existence of lethal myocardial reperfusion injury in man, suggesting that 40%-50% of the final reperfused myocardial infarct may actually be due to myocardial reperfusion injury. Intensive analysis of the signal transduction pathways underlying IPost has identified similarities with the signaling pathways underlying its preischemic counterpart, ischemic preconditioning. In this article, the reperfusion injury salvage kinase pathway and the more recently described survivor activating factor enhancement pathway, two apparently distinct signaling pathways that actually interact to convey the IPost stimulus from the cell surface to the mitochondria, where many of the prosurvival and death signals appear to converge. The elucidation of the reperfusion signaling pathways underlying IPost may result in the identification of novel pharmacological targets for cardioprotection.
Hausenloy
Derek J
DJ
The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, United Kingdom. d.hausenloy@ucl.ac.uk
Lecour
Sandrine
S
Yellon
Derek M
DM
D000818:Animals; D006801:Humans; D057775:Ischemic Postconditioning; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D010770:Phosphotransferases / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha
D033681:Mitochondrial Membrane Transport Proteins; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D010770:Phosphotransferases