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Genetic deletion of the adaptor protein p66Shc increases susceptibility to short-term ischaemic myocardial injury via intracellular salvage pathways

Akhmedov, Alexander ; Montecucco, Fabrizio ; Braunersreuther, Vincent ; Camici, Giovanni G. ; Jakob, Philipp ; Reiner, Martin F. ; Glanzmann, Martina ; Burger, Fabienne ; Paneni, Francesco ; Galan, Katia ; Pelli, Graziano ; Vuilleumier, Nicolas ; Belin, Alexandre ; Vallée, Jean-Paul ; Mach, Francois ; Lüscher, Thomas F.

In: European Heart Journal, 2015, vol. 36, no. 8, p. 516-526

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    Titre
    • Genetic deletion of the adaptor protein p66Shc increases susceptibility to short-term ischaemic myocardial injury via intracellular salvage pathways
    Auteur
    • Akhmedov, Alexander. Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland
    • Montecucco, Fabrizio. Division of Cardiology, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland
    • Braunersreuther, Vincent. Division of Cardiology, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland
    • Camici, Giovanni G.. Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland
    • Jakob, Philipp. Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland
    • Reiner, Martin F.. Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland
    • Glanzmann, Martina. Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland
    • Burger, Fabienne. Division of Cardiology, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland
    • Paneni, Francesco. Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland
    • Galan, Katia. Division of Cardiology, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland
    • Pelli, Graziano. Division of Cardiology, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland
    • Vuilleumier, Nicolas. Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Switzerland
    • Belin, Alexandre. Department of Radiology, CIBM, Geneva University Hospital, Geneva, Switzerland
    • Vallée, Jean-Paul. Department of Radiology, CIBM, Geneva University Hospital, Geneva, Switzerland
    • Mach, Francois. Division of Cardiology, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland
    • Lüscher, Thomas F.. Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • European Heart Journal, 2015, vol. 36, no. 8, p. 516-526. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:303199
    Summary
    Genetic deletion of p66Shc, as shown in the present study, leads to increased myocardial infarction in response to short-term ischaemia and reperfusion. Therefore, heart-specific activation of p66Shc protein may represent a promising novel strategy to prevent ischaemic and reperfusion myocardial injury. In particular, pharmacological modulation of apoptosis via myocardial salvage pathways involving p66Shc might be a promising approach to limit short-term ischaemic injury, for instance in patients with acute coronary syndrome (ACS) from the time of symptom onset to percutaneous coronary intervention. However, the present study also adds complexity to the use of this pathway as a therapeutic target. Indeed, given the different effects of activation and silencing of p66Shc in different cells, tissues and organs, tissue selective inhibition would be required. Indeed, while short-term activation might be protective in the context of an ACS, long-term inhibition may prevent endothelial dysfunction, atherosclerosis, and diabetic vascular disease. Obviously, this complexity also raises safety concerns for the potential use of p66Shc in acute myocardial infarction that need to be clarified by additional research