MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy

Author(s):Show less -

Pinto Ferreira, Ludmila Rodrigues ^{[1, 2, 3]} ; Frade, Amanda Farage ^{[1, 2, 3]} ; Barros Santos, Ronaldo Honorato ^[4] ; Teixeira, Priscila Camillo ^{[1, 2, 3]} ; Baron, Monique Andrade ^{[1, 2, 3]} ; Navarro, Isabela Cunha ^{[1, 2, 3]} ; Benvenuti, Luiz Alberto ^[5] ; Fiorelli, Alfredo Inacio ^[4] ; Bocchi, Edimar Alcides ^[4] ; Stolf, Noedir Antonio ^[4] ; Chevillard, Christophe ^[6] ; Kalil, Jorge ^{[1, 3]} ; Cunha-Neto, Edecio ^{[1, 2, 3]}

Affiliation

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

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

^[3] INCT, Inst Invest Immunol, BR-05403001 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Heart Inst InCor, Div Surg, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Sch Med, Heart Inst InCor, Div Pathol, Sao Paulo - Brazil

^[6] Aix Marseille Univ, Fac Med, INSERM, U906, Marseille - France

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF CARDIOLOGY; v. 175, n. 3, p. 409-417, AUG 20 2014.
• Web of Science Citations: 33

Abstract

Background/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 inmyocardial 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. Conclusion: 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 13/50302-3 - Identification of predictive / prognostic genetic signature in Chagas cardiomyopathy: a systems biology approach
• Grantee: Edecio Cunha Neto
• Support type: Regular Research Grants
• FAPESP's process: 12/08107-6 - Analysis of expression of host microRNAs during infection with Trypanosoma cruzi and Chagas Disease cardiomyopathy
• Grantee: Edecio Cunha Neto
• Support type: Regular Research Grants
• FAPESP's process: 08/57881-0 - Institute for Investigation in Immunology
• Grantee: Jorge Elias Kalil Filho
• Support type: Research Projects - Thematic Grants