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

Memórias do Instituto Oswaldo Cruz

Mariana C Waghabi²  Robson Coutinho-silva¹  Jean-jacques Feige¹  Maria De Lourdes Higuchi¹  David Becker¹  Geoffrey Burnstock¹  Tânia C De Araújo-jorge² 

[1] ,Instituto Oswaldo Cruz-Fiocruz Laboratório de Inovações Terapêuticas Rio de Janeiro RJ ,Brasil

关键词: gap junction;    heart;    Chagas disease;    transforming growth factor- β;    connexin 43;   

DOI  :  10.1590/S0074-02762009000800004

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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