title: MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes.
abstract: 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.
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, iii-INCT, São Paulo, Brazil.
authors.forename: Isabela Cunha
authors.initials: IC
authors.lastname: Navarro
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, iii-INCT, São Paulo, Brazil.
authors.forename: Frederico Moraes
authors.initials: FM
authors.lastname: Ferreira
authors.affiliation: Department of Clinical Analyses and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Helder I
authors.initials: HI
authors.lastname: Nakaya
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, iii-INCT, São Paulo, Brazil.
authors.forename: Monique Andrade
authors.initials: MA
authors.lastname: Baron
authors.affiliation: Laboratory of Biology of Interactions, Oswaldo Cruz Institute-FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Gláucia
authors.initials: G
authors.lastname: Vilar-Pereira
authors.affiliation: Laboratory of Biology of Interactions, Oswaldo Cruz Institute-FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Isabela Resende
authors.initials: IR
authors.lastname: Pereira
authors.affiliation: Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Pathology, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Ana Maria Gonçalves
authors.initials: AM
authors.lastname: Silva
authors.affiliation: Hospital Sírio-Libanês, São Paulo, Brazil.
authors.forename: Juliana Monte
authors.initials: JM
authors.lastname: Real
authors.affiliation: Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; Department of Pathology, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Thales
authors.initials: T
authors.lastname: De Brito
authors.affiliation: INSERM, U906, Aix-Marseille University AMU, Faculté de Médecine, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chevillard
authors.affiliation: Laboratory of Biology of Interactions, Oswaldo Cruz Institute-FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Joseli
authors.initials: J
authors.lastname: Lannes-Vieira
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, iii-INCT, São Paulo, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, iii-INCT, São Paulo, Brazil.
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, iii-INCT, São Paulo, Brazil.
authors.forename: Ludmila Rodrigues Pinto
authors.initials: LR
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000378:metabolism* / Q000473:pathology; D004562:Electrocardiography; D005260:Female; D020869:Gene Expression Profiling; D006321:Heart / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D025341:Principal Component Analysis; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D059467:Transcriptome / Q000235:genetics*; D014349:Trypanosoma cruzi
chemical_list: D035683:MicroRNAs