Gap junction reduction in cardiomyocytes following transforming growth factor-â treatment and Trypanosoma cruzi infection
Mem. Inst. Oswaldo Cruz
; 104(8): 1083-1090, Dec. 2009. ilus, tab
Artigo
em Inglês
| LILACS
| ID: lil-538167
Biblioteca responsável:
BR1.1
ABSTRACT
Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-â (TGF-â). 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-â T. cruzi, or SB-431542, an inhibitor of TGF-â receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-â signalling had been shown previously to be highly activated. We demonstrated that TGF-â 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-â 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-â 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.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Contexto em Saúde:
ODS3 - Saúde e Bem-Estar
/
Doenças Negligenciadas
Problema de saúde:
Meta 3.3: Acabar com as doenças tropicais negligenciadas e combater as doenças transmissíveis
/
Doença de Chagas
/
Doenças Negligenciadas
Base de dados:
LILACS
Assunto principal:
Benzamidas
/
Fator de Crescimento Transformador beta
/
Doença de Chagas
/
Receptores de Fatores de Crescimento Transformadores beta
/
Junções Comunicantes
/
Miócitos Cardíacos
/
Dioxóis
Limite:
Animais
/
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
Medicina Tropical
/
Parasitologia
Ano de publicação:
2009
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
Brasil
/
França
/
Reino Unido
Instituição/País de afiliação:
Institut National de la Santé et de la Recherche Médicale/FR
/
Instituto Oswaldo Cruz-Fiocruz/BR
/
Universidade de São Paulo/BR
/
University College London/GB
/
University College Medical School/GB