@article{discovery1311106, note = {All the contents of Mem{\'o}rias do Instituto Oswaldo Cruz journal, except where otherwise noted, is licensed under a Creative Commons Attribution License (CC-BY).}, journal = {Mem{\'o}rias do Instituto Oswaldo Cruz}, publisher = {FUNDACO OSWALDO CRUZ}, title = {Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection}, month = {December}, volume = {104}, pages = {1083--1090}, number = {8}, year = {2009}, abstract = {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.}, author = {Waghabi, MC and Coutinho-Silva, R and Feige, JJ and Higuchi, MD and Becker, D and Burnstock, G and de Araujo-Jorge, TC}, url = {http://www.scielo.br/scielo.php?pid=0074-0276&script=sci\%5fserial}, keywords = {gap junction, heart, Chagas disease, transforming growth factor-beta, connexin 43, PARASITE CYCLE COMPLETION, CHAGAS HEART-DISEASE, INTERCELLULAR COMMUNICATION, VENTRICULAR MYOCARDIUM, CONNEXIN43 EXPRESSION, DOWN-REGULATION, MESSENGER-RNA, P2 RECEPTORS, TGF-BETA, IN-VITRO}, issn = {0074-0276} }