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.
