Ludmila Rodrigues Pinto Ferreira1, Amanda Farage Frade1, Ronaldo Honorato Barros Santos2, Priscila Camillo Teixeira1, Monique Andrade Baron1, Isabela Cunha Navarro1, Luiz Alberto Benvenuti3, Alfredo Inácio Fiorelli2, Edimar Alcides Bocchi2, Noedir Antonio Stolf2, Christophe Chevillard4, Jorge Kalil5, Edecio Cunha-Neto6. 1. 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. 2. Division of Surgery, Heart Institute (InCor), University of São Paulo, School of Medicine, São Paulo, Brazil. 3. Division of Pathology, Heart Institute (InCor), University of São Paulo, School of Medicine, São Paulo, Brazil. 4. INSERM, U906, Aix-Marseille University AMU, Faculté de Médecine, Marseille, France. 5. 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. 6. 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.
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 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. 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.
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 in myocardial tissue samples of CCC patients in comparison to DCMpatients 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.
Authors: Sribalasubashini Muralimanoharan; Cun Li; Ernesto S Nakayasu; Cameron P Casey; Thomas O Metz; Peter W Nathanielsz; Alina Maloyan Journal: J Mol Cell Cardiol Date: 2017-06-19 Impact factor: 5.000
Authors: Bijay K Jha; Sanjay Varikuti; Abhay R Satoskar; Bradford S McGwire; Gabriella R Seidler; Greta Volpedo Journal: Infect Immun Date: 2020-06-22 Impact factor: 3.441