MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes

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Navarro, Isabela Cunha ^{[1, 2, 3]} ; Ferreira, Frederico Moraes ^{[1, 2, 3]} ; Nakaya, Helder I. ^[4] ; Baron, Monique Andrade ^{[1, 2, 3]} ; Vilar-Pereira, Glaucia ^[5] ; Pereira, Isabela Resende ^[5] ; Goncalves Silva, Ana Maria ^{[6, 7]} ; Real, Juliana Monte ^[8] ; De Brito, Thales ^{[6, 7]} ; Chevillard, Christophe ^[9] ; Lannes-Vieira, Joseli ^[5] ; Kalil, Jorge ^{[1, 2, 3]} ; Cunha-Neto, Edecio ^{[1, 2, 3]} ; Pinto Ferreira, Ludmila Rodrigues ^{[1, 2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Heart Inst InCor, Immunol Lab, Sch Med, Sao Paulo - Brazil

^[3] Iii INCT, Inst Investigat Immunol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Clin Anal & Toxicol, Sch Pharmaceut Sci, Sao Paulo - Brazil

^[5] Fiocruz MS, Inst Oswaldo Cruz, Lab Biol Interact, BR-21045900 Rio De Janeiro - Brazil

^[6] Univ Sao Paulo, Inst Trop Med, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo - Brazil

^[8] Hosp Sirio Libanes, Sao Paulo - Brazil

^[9] Aix Marseille Univ, Fac Med, INSERM, U906, Marseille - France

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 9, n. 6 JUN 2015.
• Citações Web of Science: 11

Resumo

Chagas disease is caused by the parasite Trypanosoma cruzi, and it begins with a short acute phase characterized by high parasitemia followed by a life-long chronic phase with scarce parasitism. Cardiac involvement is the most prominent manifestation, as 30% of infected subjects will develop abnormal ventricular repolarization with myocarditis, fibrosis and cardiomyocyte hypertrophy by undefined mechanisms. Nevertheless, follow-up studies in chagasic patients, as well as studies with murine models, suggest that the intensity of clinical symptoms and pathophysiological events that occur during the acute phase of disease are associated with the severity of cardiac disease observed during the chronic phase. In the present study we investigated the role of microRNAs (miRNAs) in the disease progression in response to T. cruzi infection, as alterations in miRNA levels are known to be associated with many cardiovascular disorders. We screened 641 rodent miRNAs in heart samples of mice during an acute infection with the Colombiana T.cruzi strain and identified multiple miRNAs significantly altered upon infection. Seventeen miRNAs were found significantly deregulated in all three analyzed time points post infection. Among these, six miRNAs had their expression correlated with clinical parameters relevant to the disease, such as parasitemia and maximal heart rate-corrected QT (QTc) interval. Computational analyses identified that the gene targets for these six miRNAs were involved in networks and signaling pathways related to increased ventricular depolarization and repolarization times, important factors for QTc interval prolongation. The data presented here will guide further studies about the contribution of microRNAs to Chagas heart disease pathogenesis. (AU)

• Processo FAPESP: 13/50302-3 - Identificação de uma assinatura genética preditiva / prognóstica na Doença de Chagas: abordagem de biologia de sistemas
• Beneficiário: Edecio Cunha Neto
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/08107-6 - Análise da expressão de microRNAs do hospedeiro durante a infecção com o Trypanosoma cruzi e a cardiopatia chagásica crônica
• Beneficiário: Edecio Cunha Neto
• Linha de fomento: Auxílio à Pesquisa - Regular