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- Title
β-Catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts
- Authors
Masuelli, Laura; Bei, Roberto; Sacchetti, Pamela; Scappaticci, Ilaria; Francalanci, Paola; Albonici, Loredana; Coletti, Anna; Palumbo, Camilla; Minieri, Marilena; Fiaccavento, Roberta; Carotenuto, Felicia; Fantini, Cristina; Carosella, Luciana; Modesti, Andrea; Di Nardo, Paolo
- 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; β-catenin is increased and accumulated in intercalated disks depriving cardiomyocyte nuclei of fundamental signals. The accumulation of β-catenin is post-translationally regulated by an increased Wnt expression, a simultaneous decrease in glycogen synthase kinase 3β (GSK3β) 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 β-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.
- Subjects
HEART cells; EXTRACELLULAR matrix; HYPERTROPHIC cardiomyopathy; CELL adhesion
- Publication
Cardiovascular Research, 2003, Vol 60, Issue 2, p376
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/j.cardiores.2003.08.005