Defective intercellular adhesion complex in myocardium predisposes to infarct rupture in humans
| Autor: | W. Matthijs Blankesteijn, Mat J.A.P. Daemen, Peter Lijnen, J. Willem Voncken, Jos F.M. Smits, H. T. M. Vervoort‐Peters, Jagat Narula, Susanne W.M. van den Borne, Vivian E. H. Dahlmans |
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| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Genetically modified mouse
Male Pathology medicine.medical_specialty Heart Rupture Mice Risk Factors medicine Cadaver Myocyte Animals Humans Myocytes Cardiac Myocardial infarction cardiovascular diseases Cell adhesion Aged Heart Rupture Post-Infarction Aged 80 and over business.industry Myocardium Catenins Middle Aged medicine.disease Cadherins Intercellular Adhesion Molecule-1 medicine.anatomical_structure Case-Control Studies Circulatory system Models Animal cardiovascular system Immunohistochemistry Female Cardiology and Cardiovascular Medicine Intercalated disc business |
| Zdroj: | Journal of the American College of Cardiology, 51(22), 2184-2192. Elsevier USA |
| ISSN: | 0735-1097 |
| Popis: | Objectives Our goal was to evaluate intercellular adhesion complex proteins in myocardium in human infarct rupture. Background Infarct rupture, a fatal complication of myocardial infarction (MI), has been attributed to a defective cell adhesion complex in a transgenic mouse model. Methods Heart samples were collected from autopsies from infarct rupture and control (nonrupture) MI patients. Both infarcted and remote areas were included. Cell adhesion proteins including αE-catenin, β-catenin, γ-catenin, and N-cadherin were characterized by immunohistochemistry and immunoblotting. Genetic analysis was undertaken to evaluate mutations and polymorphisms in the αE-catenin gene. In addition, infarct rupture was studied in transgenic mice heterozygous for αE-catenin C-terminal deficiency, mimicking the situation in human infarct rupture patients. Results No αE-catenin was detected in 70% of remote samples of infarct rupture hearts compared with 20% in control MI by immunohistochemistry. The immunoblot analysis confirmed a significant reduction in remote areas, and complete absence of αE-catenin in infarct areas from infarct rupture patients. No mutation or polymorphism of the αE-catenin gene was discovered. Other cell adhesion proteins were not significantly affected in remote areas of infarct rupture hearts. Three-fourths of the heterozygous αE-catenin C-terminal truncated mice died of infarct rupture, compared with one-fourth of the wild-type littermates. Conclusions The data show a reduced expression and defective localization of αE-catenin in the intercalated disc region in patients dying of infarct rupture. The mechanism of lower expression of αE-catenin remains to be elucidated. |
| Databáze: | OpenAIRE |
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