β-Catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts

Laura Masuelli, Roberto Bei, Pamela Sacchetti, Ilaria Scappaticci, Paola Francalanci, Loredana Albonici, Anna Coletti, Camilla Palumbo, Marilena Minieri, Roberta Fiaccavento, Felicia Carotenuto, Cristina Fantini, Luciana Carosella, Andrea Modesti, Paolo Di Nardo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)376-387
Number of pages12
JournalCardiovascular Research
Volume60
Issue number2
DOIs
Publication statusPublished - Nov 1 2003

Keywords

  • Cardiomyopathy
  • Catenin
  • Cell adhesion
  • Histopathology
  • Intercalated disks

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Masuelli, L., Bei, R., Sacchetti, P., Scappaticci, I., Francalanci, P., Albonici, L., Coletti, A., Palumbo, C., Minieri, M., Fiaccavento, R., Carotenuto, F., Fantini, C., Carosella, L., Modesti, A., & Di Nardo, P. (2003). β-Catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts. Cardiovascular Research, 60(2), 376-387. https://doi.org/10.1016/j.cardiores.2003.08.005