Key result
Hypertrophic cardiomyopathy is associated with increased beta-catenin accumulation in disorganized intercalated disks, driven by altered Wnt, GSK3beta, and APC expression.
No immediate clinical implications for HCM; leaves open Wnt/beta-catenin targeting for future mechanistic studies.
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. 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 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.
No takes yet. Share an insight, caveat, or question.
Laura Masuelli (2003) studied Hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy was evaluated on Cardiomyocyte membrane structure and cell/extracellular matrix adhesion alterations. Hypertrophic cardiomyopathy is associated with increased beta-catenin accumulation in disorganized intercalated disks, driven by altered Wnt, GSK3beta, and APC expression.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: