Gap junction reduction in cardiomyocytes following transforming growth factor-β treatment and Trypanosoma cruzi infection


Autoria(s): Waghabi,Mariana C; Coutinho-Silva,Robson; Feige,Jean-Jacques; Higuchi,Maria de Lourdes; Becker,David; Burnstock,Geoffrey; Araújo-Jorge,Tânia C de
Data(s)

01/12/2009

Resumo

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.

Formato

text/html

Identificador

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762009000800004

Idioma(s)

en

Publicador

Instituto Oswaldo Cruz, Ministério da Saúde

Fonte

Memórias do Instituto Oswaldo Cruz v.104 n.8 2009

Palavras-Chave #gap junction #heart #Chagas disease #transforming growth factor- β #connexin 43
Tipo

journal article