Beta-catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts.
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.
Masuelli
Laura
L
Department of Experimental Medicine and Pathology, University of Rome "La Sapienza", Rome, Italy.
Bei
Roberto
R
Sacchetti
Pamela
P
Scappaticci
Ilaria
I
Francalanci
Paola
P
Albonici
Loredana
L
Coletti
Anna
A
Palumbo
Camilla
C
Minieri
Marilena
M
Fiaccavento
Roberta
R
Carotenuto
Felicia
F
Fantini
Cristina
C
Carosella
Luciana
L
Modesti
Andrea
A
Di Nardo
Paolo
P
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
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