Alterações elétricas e teciduais durante a infecção pelo T. Cruzi e avanços combinados para a caracterização funcional das junções GAP cardiovasculares e dos efeitos diretos da hipercolesterolemia no coração: alvos de novas ferramentas para o estudo da Doença de Chagas

Abstract

Since identification of Chagas Disease (CD) in 1909, a lot of effort was invested into the characterization of DC infection mechanisms, control of parasite vector and treatment of symptoms. However, after more than 100 years, there is still no effective antiparasytic treatment, especially in the chronic phase, and management of symptoms is done unespecifically for cardiomyopathies, which makes both approaches unnefective. Given the complexity of CD, investigating isolated aspects of the infection provides important cues in terms of disease etiology and mechanisms, however, integrated approaches are also necessary in order to evaluate new and more specific therapeutic strategies. In this study, we have attempted to address these issues, according to the following goals: characterization of whether changes in electrical properties of the isolated ventricular myocytes are correlated with tissue remodeling and T. cruzi persistence in CD. Besides, we studied functional properties of cardiac and vascular GAP junctions, pointing them as potential target impacting CD output. Finally, we described direct effect of hypercholesterolemia in a murine model, as a new strategy to evaluate effects of dyslipidemias in the development of CD. All together, we the data reported here will contribute to the elucidation of GAP junction functional properties and the direct role of hypercholesterolemia in heart and isolated cardiomyocytes properties. Furthermore, we have pointed new approaches that will contribute to the elucidation of CD symptoms development as well as to the influence of nutritional aspects to this disease in a more comprehensive manner.