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EH-myomesin splice isoform is a novel marker for dilated cardiomyopathy

Schoenauer, Roman ; Emmert, Maximilian ; Felley, Allison ; Ehler, Elisabeth ; Brokopp, Chad ; Weber, Benedikt ; Nemir, Mohamed ; Faggian, Giuseppe ; Pedrazzini, Thierry ; Falk, Volkmar ; Hoerstrup, Simon ; Agarkova, Irina

In: Basic Research in Cardiology, 2011, vol. 106, no. 2, p. 233-247

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    Titel
    • EH-myomesin splice isoform is a novel marker for dilated cardiomyopathy
    Autor
    • Schoenauer, Roman. Swiss Center for Regenerative Medicine, University of Zurich, Zurich, Switzerland
    • Emmert, Maximilian. Swiss Center for Regenerative Medicine, University of Zurich, Zurich, Switzerland
    • Felley, Allison. Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland
    • Ehler, Elisabeth. The Randall Division of Cell and Molecular Biophysics and the Cardiovascular Division, King's College London, London, UK
    • Brokopp, Chad. Swiss Center for Regenerative Medicine, University of Zurich, Zurich, Switzerland
    • Weber, Benedikt. Swiss Center for Regenerative Medicine, University of Zurich, Zurich, Switzerland
    • Nemir, Mohamed. Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland
    • Faggian, Giuseppe. Division of Cardiac Surgery and Cardiology, University of Verona, Verona, Italy
    • Pedrazzini, Thierry. Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland
    • Falk, Volkmar. Clinic for Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland
    • Hoerstrup, Simon. Swiss Center for Regenerative Medicine, University of Zurich, Zurich, Switzerland
    • Agarkova, Irina. Swiss Center for Regenerative Medicine, University of Zurich, Zurich, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Basic Research in Cardiology, 2011, vol. 106, no. 2, p. 233-247. Springer-Verlag
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:313175
    Summary
    The M-band is the prominent cytoskeletal structure that cross-links the myosin and titin filaments in the middle of the sarcomere. To investigate M-band alterations in heart disease, we analyzed the expression of its main components, proteins of the myomesin family, in mouse and human cardiomyopathy. Cardiac function was assessed by echocardiography and compared to the expression pattern of myomesins evaluated with RT-PCR, Western blot, and immunofluorescent analysis. Disease progression in transgenic mouse models for dilated cardiomyopathy (DCM) was accompanied by specific M-band alterations. The dominant splice isoform in the embryonic heart, EH-myomesin, was strongly up-regulated in the failing heart and correlated with a decrease in cardiac function (R=−0.86). In addition, we have analyzed the expressions of myomesins in human myocardial biopsies (N=40) obtained from DCM patients, DCM patients supported by a left ventricular assist device (LVAD), hypertrophic cardiomyopathy (HCM) patients and controls. Quantitative RT-PCR revealed that the EH-myomesin isoform was up-regulated 41-fold (P<0.001) in the DCM patients compared to control patients. In DCM hearts supported by a LVAD and HCM hearts, the EH-myomesin expression was comparable to controls. Immunofluorescent analyses indicate that EH-myomesin was enhanced in a cell-specific manner, leading to a higher heterogeneity of the myocytes' cytoskeleton through the myocardial wall. We suggest that the up-regulation of EH-myomesin denotes an adaptive remodeling of the sarcomere cytoskeleton in the dilated heart and might serve as a marker for DCM in mouse and human myocardium