© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
β-Catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts
aDepartment of Experimental Medicine and Pathology, University of Rome "La Sapienza", Rome, Italy
bDepartment of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata", Rome, Italy
cDepartment of Pathology, Bambino Gesu Children's Hospital-Research Institute Rome, Rome, Italy
dDepartment of Internal Medicine, Università di Roma Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy
eDepartment of Internal Medicine and Geriatrics, Catholic University of Sacred Heart, Rome, Italy
*Corresponding author. Tel.: +39-6-72594215; fax: +39-6-2024130. Email address: dinardo{at}med.uniroma2.it
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.
KEYWORDS Cardiomyopathy; Cell adhesion; Histopathology; Catenin
Time for primary review 26 days
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