Titre
Sarcomeric M-band alterations as a marker for human dilated cardiomyopathy
Type
abstract de conférence/colloque
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Série
European Heart Journal
Auteur(s)
Schoenauer, R.
Auteure/Auteur
Emmert, M. Y.
Auteure/Auteur
Felley, A.
Auteure/Auteur
Ehler, E.
Auteure/Auteur
Pedrazzini, T.
Auteure/Auteur
Falk, V.
Auteure/Auteur
Hoerstrup, S. P.
Auteure/Auteur
Agarkova, I.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
Titre du livre ou conférence/colloque
ESC Congress
Adresse
Stockholm, Sweden, August 28-September 01, 2010
ISBN
0195-668X
Statut éditorial
Publié
Date de publication
2010
Volume
31
Première page
635
Peer-reviewed
Oui
Langue
anglais
Notes
Publication type : Meeting Abstract
Résumé
Purpose: The M-band is an important cytoskeletal structure in the centre of the sarcomere, believed to cross-link the thick filament lattice. Its main components are three closely related modular proteins from the myomesin gene family: Myomesin, M-protein and myomesin-3. Each muscle is characterized by its unique M-band protein composition, depending on the contractile parameters of a particular fiber. To investigate the role of the M-band in one of the most relevant and clinically increasing cardiac diseases, we analyzed the expression of myomesin proteins in dilated cardiomyopathy (DCM).Methods: In a previous study we analyzed mouse models suffering from DCM, demonstrating that the embryonic heart specific EH-myomesin splicing isoform was up-regulated directly corresponding to the degree of cardiac dysfunction and ventricular dilation. Based on this study, human ventricular and atrial samples (n=32) were obtained during heart surgery after informed consent and approval by an institutional review board. Patients were aged 30-70 years and suffered from dilated cardiomyopathy (DCM;n=13), Hypertrophic Cardiomyopathy (HCM;n=10) or served as controls (n=9). Patients suffering from DCM or HCM were in endstage heart-failure (NYHA III-IV) and either underwent heart transplantation or Left Ventricular Assist Device (LVAD) implantation. Heart samples from patients who underwent valve surgery or congenital heart surgery served as controls. Heart Samples were analyzed using RT-PCR, Western blot, and immunofluorescence.Results: By investigating the expression pattern of myomesins, we found that DCM is accompanied by specific M-band alterations, which were more pronounced in ventricular samples compared to the atrium. Changes in the amounts of different myomesins during DCM occurred in a cell-specific manner, leading to a higher heterogeneity of the cytoskeleton in cardiomyocytes through the myocardial wall with some cells switching completely to an embryonic phenotype.Conclusions: Here we present that the embryonic heart specific EH-myomesin isoform is up-regulated in human DCM. The alterations of the M-band protein composition might be part of a general adaptation of the sarcomeric cytoskeleton to unfavorable working conditions in the failing heart and may modify the mechanical properties of the cardiomyocytes. We suggest that the upregulation of EH-myomesin might play a pivotal role in DCM and might support classical imagingas a novel sarcomeric marker for this disease.
PID Serval
serval:BIB_84711F2E4FF9
Date de création
2011-04-13T08:18:55.068Z
Date de création dans IRIS
2025-05-21T00:43:06Z