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
Article
Dans Anglais
| LILACS
| ID: lil-538167
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.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Benzamides
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Facteur de croissance transformant bêta
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Maladie de Chagas
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Récepteurs TGF-bêta
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Jonctions communicantes
/
Myocytes cardiaques
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Dioxoles
Limites du sujet:
Animaux
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Femelle
/
Humains
/
Mâle
langue:
Anglais
Texte intégral:
Mem. Inst. Oswaldo Cruz
Thème du journal:
Médecine tropicale
/
Parasitologie
Année:
2009
Type:
Article
/
descriptif de projet
Pays d'affiliation:
Brésil
/
France
/
Royaume-Uni
Institution/Pays d'affiliation:
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
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