title: Beta-catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Experimental Medicine and Pathology, University of Rome "La Sapienza", Rome, Italy.
authors: Laura
authors: L
authors: Masuelli
authors: Roberto
authors: R
authors: Bei
authors: Pamela
authors: P
authors: Sacchetti
authors: Ilaria
authors: I
authors: Scappaticci
authors: Paola
authors: P
authors: Francalanci
authors: Loredana
authors: L
authors: Albonici
authors: Anna
authors: A
authors: Coletti
authors: Camilla
authors: C
authors: Palumbo
authors: Marilena
authors: M
authors: Minieri
authors: Roberta
authors: R
authors: Fiaccavento
authors: Felicia
authors: F
authors: Carotenuto
authors: Cristina
authors: C
authors: Fantini
authors: Luciana
authors: L
authors: Carosella
authors: Andrea
authors: A
authors: Modesti
authors: Paolo
authors: P
authors: Di Nardo
mesh_terms: D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002648:Child; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D017491:Genes, APC; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3