Gap junction reduction in cardiomyocytes following transforming growth factor-â treatment and Trypanosoma cruzi infection

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.

Políticas sanitarias para el control de la enfermedad de Chagas / Sanitary policies for the control of Chagas' disease

Se tratan aspectos de las políticas sanitarias de la enfermedad de Chagas, enfatizándose la necesidad de adecuarlas en base al diagnóstico de situación - para determinar la importancia real de la enfermedad- y a la realidad política, territorial, social, cultural y educativa de las comunidades en donde se ejecutarán las acciones. Se describe el caso argentino, para comparaciones con otros países y el aprovechamiento de experiencias: el problema chagásico en las distintas zonas endémicas dentro de la Argentina y la organización del Servicio Nacional de Lucha contra la Enfermedad de Chagas, analizándose las ventajas de su estructura vertical (citándose recomendaciones internacionales). Se señala la necesidad de que las acciones operativas de la lucha contra el Chagas en el país sean transferidad hacia las jurisdicciones provinciales, quedándole reservada al Servicio Nacional la conducción y ejecución de las acciones