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
in En
| LILACS
| ID: lil-538167
Responsible library:
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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.
Key words
Full text:
1
Index:
LILACS
Main subject:
Benzamides
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Transforming Growth Factor beta
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Chagas Disease
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Receptors, Transforming Growth Factor beta
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Gap Junctions
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Myocytes, Cardiac
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Dioxoles
Limits:
Animals
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Female
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Humans
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Male
Language:
En
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
MEDICINA TROPICAL
/
PARASITOLOGIA
Year:
2009
Type:
Article
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Project document