Objective: To evaluate whether cardiomyocyte membrane structure and cell/extracellular matrix adhesion alterations perturb the cadherin/ catenin complex in the hypertrophic cardiomyopathy (HCM). Methods: Hypertrophic cardiomyopathic hamster (UM-X7.1 strain) and human hearts were studied by light and electron microscopy, Northern and Western blot analyses and immunohistochemistry. Results: Intercalated disks are disorganized in both hamster and human cardiomyopathic hearts-, beta-catenin is increased and accumulated in intercalated disks depriving cardiomyocyte nuclei of fundamental signals. The accumulation of beta-catenin is post-translationally regulated by an increased Wnt expression, a simultaneous decrease in glycogen synthase kinase 3beta (GSK3beta) expression and a different expression pattern of adenomatous polyposis coli (APC) isoforms. Conclusion: The reorganization of cell/cell adhesion in cardiomyopathic hearts is mainly contributed by the cadherin/catenin system, which is differently regulated to sustain cell structural rather than signalling needs causing considerable consequences in the determination of cardiomyocyte phenotype and clinical outcome. The accumulation of beta-catenin in intercalated disks could concur to increase myocardial wall stiffness and left ventricular end-diastolic pressure (LVEDP) in hypertrophic cardiomyopathic hamster and human hearts. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
beta-Catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts / Masuelli, Laura; R., Bei; Sacchetti, Pamela; I., Scappaticci; P., Francalanci; L., Albonici; A., Coletti; C., Palumbo; M., Minieri; R., Fiaccavento; F., Carotenuto; C., Fantini; L., Carosella; A., Modesti; P., Di Nardo. - In: CARDIOVASCULAR RESEARCH. - ISSN 0008-6363. - 60:2(2003), pp. 376-387. [10.1016/j.cardiores.2003.08.005]
beta-Catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts
MASUELLI, Laura;SACCHETTI, PAMELA;
2003
Abstract
Objective: To evaluate whether cardiomyocyte membrane structure and cell/extracellular matrix adhesion alterations perturb the cadherin/ catenin complex in the hypertrophic cardiomyopathy (HCM). Methods: Hypertrophic cardiomyopathic hamster (UM-X7.1 strain) and human hearts were studied by light and electron microscopy, Northern and Western blot analyses and immunohistochemistry. Results: Intercalated disks are disorganized in both hamster and human cardiomyopathic hearts-, beta-catenin is increased and accumulated in intercalated disks depriving cardiomyocyte nuclei of fundamental signals. The accumulation of beta-catenin is post-translationally regulated by an increased Wnt expression, a simultaneous decrease in glycogen synthase kinase 3beta (GSK3beta) expression and a different expression pattern of adenomatous polyposis coli (APC) isoforms. Conclusion: The reorganization of cell/cell adhesion in cardiomyopathic hearts is mainly contributed by the cadherin/catenin system, which is differently regulated to sustain cell structural rather than signalling needs causing considerable consequences in the determination of cardiomyocyte phenotype and clinical outcome. The accumulation of beta-catenin in intercalated disks could concur to increase myocardial wall stiffness and left ventricular end-diastolic pressure (LVEDP) in hypertrophic cardiomyopathic hamster and human hearts. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
