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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060
EISSN: 1678-8060
Vol. 104, No. 8, 2009, pp. 1083-1090
Bioline Code: oc09222
Full paper language: English
Document type: Research Article
Document available free of charge

Memórias do Instituto Oswaldo Cruz, Vol. 104, No. 8, 2009, pp. 1083-1090

 en Gap junction reduction in cardiomyocytes following transforming growth factor- β treatment and Trypanosoma cruzi check for this species in other resources infection
Waghabi, Mariana C; Coutinho-Silva, Robson; Feige, Jean-Jacques; Higuchi, Maria de Lourdes; Becker, David; Burnstock, Geoffrey & de Araújo-Jorge, Tânia C

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 check for this species in other resources 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.

Keywords
gap junction - heart - Chagas disease - transforming growth factor-β - connexin 43

 
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