Chagas disease is a potentially life-threatening illness caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi). The main clinical consequence is the development of chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy. It is already known that CCC patients have a worse prognosis than those with other cardiomyopathies with non inflammatory etiology. However, the factors that define the progression to CCC or maintenance in the asymptomatic indeterminate form of the disease are still incompletely understood. Several studies have evaluated the global gene and proteomic expression profiles, as well as changes occurring in acute and chronic Chagas disease, both in animal models and humans. Such changes result from regulation established at different levels of gene expression and may be relevant for the prognosis of the disease. In this context, several studies have indicated the importance of small non-coding RNA molecules, called microRNAs, which play regulatory functions in many cellular processes. Its action is given by the association to a target messenger RNA (mRNA), inhibiting its translation or degrading this transcript. Imbalances in the expression of microRNAs have been associated with the genesis of several pathologies, like cardiopathies and parasitic diseases. Our hypothesis is that acute infection by T. cruzi modulates the expression of microRNAs of the host. Since important changes in the gene expression profile of the myocardium are common in the acute and chronic phases of Chagas disease, the aim of this project is to evaluate the expression profile of microRNAs during the acute phase of infection by T. cruzi in mice. We will extract microRNAs from murine myocardial tissue 6, 12 or 24 days after infection. The microRNA expression profile will be determined by the TaqMan Low Density Array (TLDA) technology. Possible target genes will be predicted by bioinformatics approaches and the resulting data will be associated with previously done gene and protein analyses, in order to improve the understanding of Chagas disease pathogenesis.
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