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Analysis of expression of host microRNAs during infection with Trypanosoma cruzi and Chagas Disease cardiomyopathy

Grant number: 12/08107-6
Support type:Regular Research Grants
Duration: September 01, 2012 - November 30, 2014
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Edecio Cunha Neto
Grantee:Edecio Cunha Neto
Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers:Jorge Elias Kalil Filho ; Ludmila Rodrigues Pinto Ferreira Camargo

Abstract

Chagas disease, endemic in Latin America, is caused by an infection with the parasite Trypanosoma cruzi. The main clinical consequence of infection by the parasite is the development of a chronic Chagas cardiomyopathy (CCC). About 30% of infected patients develop CCC, 5 to 30 years after initial infection. CCC has a worse prognosis than other causes of cardiomyopathy. To date, there are no markers to identify the population most at risk to develop CCC, which is characterized by a myocarditis rich in T cells and macrophages, hypertrophy and fibrosis. Studies of analysis of gene expression in animals and patients have identified modulation of several pathways related to inflammation, signaling and energy metabolism. However, we still don't know the molecular mechanisms that cause this modulation. Recently it was shown that microRNAs (miRNAs), small RNA molecules are involved in regulating gene expression of virtually all cellular processes. MiRNAs contain 22 nucleotides in length and bind to partially complementary sequences present in the 3' untranslated regions of specific messenger RNAs (mRNA) or target mRNA. This pairing between the miRNA and its target mRNA leads to cleavage of the latter or translation inhibition resulting in silencing of gene expression. The modulation of expression of certain miRNAs is related to the physiology and pathophysiology of the cardiovascular system. MiRNAs have also been identified as important plasma biomarkers as they are secreted by cells or released during tissue damage. It is known that intracellular pathogens such as Cryptosporidium and Toxoplasma rapidly alter the miRNAs expression in host cells. Our hypothesis is that changes in the expression of different miRNAs induced by T. cruzi during the acute phase of infection may be associated with the development of CCC. Therefore, we hypothesized that the expression pattern of microRNAs during the chronic phase may reflect the expression profile of miRNAs in cardiac tissue induced by the presence of the parasite in the acute phase. The corollary of our hypothesis is that the profile of miRNAs is important in the establishment of a clinical picture of myocarditis and / or hypertrophy during acute infection with T. cruzi and during CCC. In addition, to evaluate whether miRNAs can be used as biomarkers of disease severity and progression to CCC, we will study the profile of miRNAs present in the plasma of chagasic patients from different clinical forms and also in mice acutely infected with T.cruzi. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NAVARRO, ISABELA CUNHA; FERREIRA, FREDERICO MORAES; NAKAYA, HELDER I.; BARON, MONIQUE ANDRADE; VILAR-PEREIRA, GLAUCIA; PEREIRA, ISABELA RESENDE; GONCALVES SILVA, ANA MARIA; REAL, JULIANA MONTE; DE BRITO, THALES; CHEVILLARD, CHRISTOPHE; LANNES-VIEIRA, JOSELI; KALIL, JORGE; CUNHA-NETO, EDECIO; PINTO FERREIRA, LUDMILA RODRIGUES. MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes. PLoS Neglected Tropical Diseases, v. 9, n. 6 JUN 2015. Web of Science Citations: 11.
PINTO FERREIRA, LUDMILA RODRIGUES; FRADE, AMANDA FARAGE; BARROS SANTOS, RONALDO HONORATO; TEIXEIRA, PRISCILA CAMILLO; BARON, MONIQUE ANDRADE; NAVARRO, ISABELA CUNHA; BENVENUTI, LUIZ ALBERTO; FIORELLI, ALFREDO INACIO; BOCCHI, EDIMAR ALCIDES; STOLF, NOEDIR ANTONIO; CHEVILLARD, CHRISTOPHE; KALIL, JORGE; CUNHA-NETO, EDECIO. MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy. INTERNATIONAL JOURNAL OF CARDIOLOGY, v. 175, n. 3, p. 409-417, AUG 20 2014. Web of Science Citations: 33.

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