Author | Waghabi, Mariana C. | |
Author | Silva, Robson Coutinho | |
Author | Feige, Jean-Jacques | |
Author | Higuichi, Maria de Lourdes | |
Author | Becker, David | |
Author | Burnstock, Geoffrey | |
Author | Araujo-Jorge, Tania C. | |
Access date | 2018-09-21T18:37:48Z | |
Available date | 2018-09-21T18:37:48Z | |
Document date | 2009 | |
Citation | WAGHABI, Mariana C. et al. Gap junction reduction in cardiomyocytes following transforming growth factor- β treatment and Trypanosoma cruzi infection. Mem. Inst Oswaldo Cruz, v.104, n.8, p.1083-1090, Dec. 2009. | pt_BR |
ISSN | 0074-0276 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/28974 | |
Language | eng | pt_BR |
Publisher | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. | pt_BR |
Rights | open access | |
Subject in Portuguese | Doença de Chagas | pt_BR |
Subject in Portuguese | Coração | pt_BR |
Subject in Portuguese | Conexina 43 | pt_BR |
Subject in Portuguese | Fatores de Crescimento Transformadores-β | pt_BR |
Title | Gap junction reduction in cardiomyocytes following transforming growth factor- β treatment and Trypanosoma cruzi infection | pt_BR |
Type | Article | |
Abstract | Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-β (TGF-β). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-β T. cruzi, or SB-431542, an inhibitor of TGF-β receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-β signalling had been shown previously to be highly activated. We demonstrated that TGF-β treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-β secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-β levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações Terapêuticas, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil / Autonomic Neuroscience Centre. Royal Free and University College Medical School. Rowland Hill Street, London, UK . | pt_BR |
Affilliation | Autonomic Neuroscience Centre. Royal Free and University College Medical School. Rowland Hill Street, London, UK / | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Institut National de la Santé et de la Recherche Médicale. Unité 878, and Commissariat à l’Énergie Atomique. Institut de Recherches en Technologies et Sciences pour le Vivant. Grenoble, France. | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Department of Anatomy and Developmental Biology. University College London. Gower Street, London, UK. | pt_BR |
Affilliation | Autonomic Neuroscience Centre. Royal Free and University College Medical School. Rowland Hill Street, London, UK . | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações Terapêuticas, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | gap junction | pt_BR |
Subject | heart | pt_BR |
Subject | transforming growth factor-β | pt_BR |
Subject | connexin 43 | pt_BR |
Subject | Chagas Disease | pt_BR |
e-ISSN | 1678-8060 | |
xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |