title: MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy.
abstract: METHODS
  Chagas disease is caused by an intracellular parasite, Trypanosoma cruzi, and it is a leading cause of heart failure in Latin America. The main clinical consequence of the infection is the development of a Chronic Chagas disease Cardiomyopathy (CCC), which is characterized by myocarditis, hypertrophy and fibrosis and affects about 30% of infected patients. CCC has a worse prognosis than other cardiomyopathies, like idiopathic dilated cardiomyopathy (DCM). It is well established that myocardial gene expression patterns are altered in CCC, but the molecular mechanisms underlying these differences are not clear. MicroRNAs are recently discovered regulators of gene expression, and are recognized as important factors in heart development and cardiovascular disorders (CD). We analyzed the expression of nine different miRNAs in myocardial tissue samples of CCC patients in comparison to DCM patients and samples from heart transplant donors. Using the results of a cDNA microarray database on CCC and DCM myocardium, signaling networks were built and nodal molecules were identified.
  
  
  RESULTS
  We observed that five miRNAs were significantly altered in CCC and three in DCM; importantly, three miRNAs were significantly reduced in CCC as compared to DCM. We observed that multiple gene targets of the differentially expressed miRNAs showed a concordant inverse expression in CCC. Significantly, most gene targets and involved networks belong to crucial disease-related signaling pathways.
  
  
  CONCLUSIONS
  These results suggest that miRNAs may play a major role in the regulation of gene expression in CCC pathogenesis, with potential implication as diagnostic and prognostic tools.
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, 05403-001, São Paulo, Brazil.
authors.forename: Ludmila Rodrigues Pinto
authors.initials: LR
authors.lastname: Ferreira
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, 05403-001, São Paulo, Brazil.
authors.forename: Amanda Farage
authors.initials: AF
authors.lastname: Frade
authors.affiliation: Division of Surgery, Heart Institute (InCor), University of São Paulo, School of Medicine, São Paulo, Brazil.
authors.forename: Ronaldo Honorato Barros
authors.initials: RH
authors.lastname: Santos
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, 05403-001, São Paulo, Brazil.
authors.forename: Priscila Camillo
authors.initials: PC
authors.lastname: Teixeira
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, 05403-001, São Paulo, Brazil.
authors.forename: Monique Andrade
authors.initials: MA
authors.lastname: Baron
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, 05403-001, São Paulo, Brazil.
authors.forename: Isabela Cunha
authors.initials: IC
authors.lastname: Navarro
authors.affiliation: Division of Pathology, Heart Institute (InCor), University of São Paulo, School of Medicine, São Paulo, Brazil.
authors.forename: Luiz Alberto
authors.initials: LA
authors.lastname: Benvenuti
authors.affiliation: Division of Surgery, Heart Institute (InCor), University of São Paulo, School of Medicine, São Paulo, Brazil.
authors.forename: Alfredo Inácio
authors.initials: AI
authors.lastname: Fiorelli
authors.affiliation: Division of Surgery, Heart Institute (InCor), University of São Paulo, School of Medicine, São Paulo, Brazil.
authors.forename: Edimar Alcides
authors.initials: EA
authors.lastname: Bocchi
authors.affiliation: Division of Surgery, Heart Institute (InCor), University of São Paulo, School of Medicine, São Paulo, Brazil.
authors.forename: Noedir Antonio
authors.initials: NA
authors.lastname: Stolf
authors.affiliation: INSERM, U906, Aix-Marseille University AMU, Faculté de Médecine, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chevillard
authors.affiliation: Division of Clinical Immunology and Allergy, University of São Paulo, School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, 05403-001, 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, 05403-001, São Paulo, Brazil.. Electronic address: edecunha@usp.br.
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002598:Chagas Cardiomyopathy / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D053263:Gene Regulatory Networks / Q000502:physiology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; C544547:MIRN1 microRNA, human; C548234:MIRN133 microRNA, human; C550906:MIRN208 microRNA, human; D035683:MicroRNAs
keywords: Chagas disease; Heart; Trypanosoma cruzi; miRNA