TY  - JOUR
UR  - http://www.scielo.br/scielo.php?pid=0074-0276&script=sci_serial
SN  - 0074-0276
JF  - Memórias do Instituto Oswaldo Cruz
A1  - Waghabi, MC
A1  - Coutinho-Silva, R
A1  - Feige, JJ
A1  - Higuchi, MD
A1  - Becker, D
A1  - Burnstock, G
A1  - de Araujo-Jorge, TC
VL  - 104
SP  - 1083
IS  - 8
N1  - All the contents of Memórias do Instituto Oswaldo Cruz journal, except where otherwise noted, is licensed under a Creative Commons Attribution License (CC-BY).
N2  - Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-beta (TGF-beta). 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-beta T. cruzi, or SB-431542, an inhibitor of TGF-beta receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-beta signalling had been shown previously to be highly activated. We demonstrated that TGF-beta 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-beta 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-beta 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.
ID  - discovery1311106
PB  - FUNDACO OSWALDO CRUZ
KW  - gap junction
KW  -  heart
KW  -  Chagas disease
KW  -  transforming growth factor-beta
KW  -  connexin 43
KW  -  PARASITE CYCLE COMPLETION
KW  -  CHAGAS HEART-DISEASE
KW  -  INTERCELLULAR COMMUNICATION
KW  -  VENTRICULAR MYOCARDIUM
KW  -  CONNEXIN43 EXPRESSION
KW  -  DOWN-REGULATION
KW  -  MESSENGER-RNA
KW  -  P2 RECEPTORS
KW  -  TGF-BETA
KW  -  IN-VITRO
TI  - Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection
AV  - public
Y1  - 2009/12//
EP  - 1090
ER  -