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.
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.
Authors: Piotr Sklepkiewicz; Takayuki Shiomi; Rajbir Kaur; Jie Sun; Susan Kwon; Becky Mercer; Peter Bodine; Ralph Theo Schermuly; Isaac George; P Christian Schulze; Jeanine M D'Armiento Journal: Circ Heart Fail Date: 2015-02-10 Impact factor: 8.790
Authors: Bih-Rong Wei; R Mark Simpson; Donald J Johann; Jennifer E Dwyer; Darue A Prieto; Mia Kumar; Xiaoying Ye; Brian Luke; Heather R Shive; Joshua D Webster; Shelley B Hoover; Timothy D Veenstra; Josip Blonder Journal: J Proteome Res Date: 2012-02-06 Impact factor: 4.466
Authors: Andre Monteiro da Rocha; Guadalupe Guerrero-Serna; Adam Helms; Carly Luzod; Sergey Mironov; Mark Russell; José Jalife; Sharlene M Day; Gary D Smith; Todd J Herron Journal: J Mol Cell Cardiol Date: 2016-09-10 Impact factor: 5.000
Authors: Margaret Anne Craig; Martin W McBride; Godfrey Smith; Sarah J George; Andrew Baker Journal: J Mol Cell Cardiol Date: 2010-02-06 Impact factor: 5.000