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Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke

Spescha, R.D. ; Klohs, J. ; Semerano, A. ; Giacalone, G. ; Derungs, R.S. ; Reiner, M.F. ; Rodriguez Gutierrez, D. ; Mendez-Carmona, N. ; Glanzmann, M. ; Savarese, G. ; Kränkel, N. ; Akhmedov, A. ; Keller, S. ; Mocharla, P. ; Kaufmann, M.R. ; Wenger, R.H. ; Vogel, J. ; Kulic, L. ; Nitsch, R.M. ; Beer, J.H. ; Peruzzotti-Jametti, L. ; Sessa, M. ; Lüscher, T.F. ; Camici, G.G.

In: European Heart Journal, 2015, vol. 36, no. 25, p. 1590-1600

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    Titel
    • Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke
    Autor
    • Spescha, R.D.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Klohs, J.. Institute for Biomedical Engineering, Swiss Federal Institute of Technology Zurich (ETHZ), Zurich, Switzerland
    • Semerano, A.. Department of Neurology, San Raffaele Scientific Institute, Milan, Italy
    • Giacalone, G.. Department of Neurology, San Raffaele Scientific Institute, Milan, Italy
    • Derungs, R.S.. Division of Psychiatry Research, University of Zurich, Schlieren, Switzerland
    • Reiner, M.F.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Rodriguez Gutierrez, D.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Mendez-Carmona, N.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Glanzmann, M.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Savarese, G.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Kränkel, N.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Akhmedov, A.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Keller, S.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Mocharla, P.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Kaufmann, M.R.. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland
    • Wenger, R.H.. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland
    • Vogel, J.. Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland
    • Kulic, L.. Division of Psychiatry Research, University of Zurich, Schlieren, Switzerland
    • Nitsch, R.M.. Division of Psychiatry Research, University of Zurich, Schlieren, Switzerland
    • Beer, J.H.. Department of Internal Medicine, Cantonal Hospital of Baden, Baden, Switzerland
    • Peruzzotti-Jametti, L.. Department of Neurology, San Raffaele Scientific Institute, Milan, Italy
    • Sessa, M.. Department of Neurology, San Raffaele Scientific Institute, Milan, Italy
    • Lüscher, T.F.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    • Camici, G.G.. Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, Schlieren CH-8952, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • European Heart Journal, 2015, vol. 36, no. 25, p. 1590-1600. Oxford University Press
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:298852
    Summary
    In light of the limited repertoire of therapeutical options available for the treatment of ischaemic stroke, the identification of novel potential targets is vital; in this respect, the present study demonstrates that the adaptor protein p66Shc holds this potential as an adjunct therapy to thrombolysis. Post-ischaemic silencing of p66Shc protein yielded beneficial effects in a mouse model of I/R brain injury underlying an interesting translational perspective for this target protein. Further, in proof-of-principle clinical experiments using PBMs, we demonstrate that p66Shc gene expression is transiently increased and that its levels correlate to short-term outcome in ischaemic stroke patients. Although these latter experiments are not directly relevant to the experiments performed in mice and in human endothelial cells, they provide novel important information about p66Shc regulation in stroke patients and set the basis for further investigations aimed at assessing the potential for p66Shc to become a novel therapeutic target as an adjunct of thrombolysis for the management of acute ischaemic stroke