ALFREDO INACIO FIORELLI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
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- MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy(2014) FERREIRA, Ludmila Rodrigues Pinto; FRADE, Amanda Farage; SANTOS, Ronaldo Honorato Barros; TEIXEIRA, Priscila Camillo; BARON, Monique Andrade; NAVARRO, Isabela Cunha; BENVENUTI, Luiz Alberto; FIORELLI, Alfredo Inacio; BOCCHI, Edimar Alcides; STOLF, Noedir Antonio; CHEVILLARD, Christophe; KALIL, Jorge; CUNHA-NETO, EdecioBackground/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.
- Infectious agents and inflammation in donated hearts and dilated cardiomyopathies related to cardiovascular diseases, Chagas' heart disease, primary and secondary dilated cardiomyopathies(2015) MANGINI, Sandrigo; HIGUCHI, Maria de Lourdes; KAWAKAMI, Joyce Tiyeko; REIS, Marcia Martins; IKEGAMI, Renata Nishiyama; PALOMINO, Suely Aparecida Pinheiro; POMERANTZEFF, Pablo Maria Alberto; FIORELLI, Alfredo Inacio; MARCONDES-BRAGA, Fabiana Goulart; BACAL, Fernando; FERREIRA, Silvia Moreira Ayub; ISSA, Victor Sarli; SOUZA, Germano Emilio Conceicao; CHIZZOLA, Paulo Roberto; BOCCHI, Edimar AlcidesBackground: Clinical and experimental conflicting data have questioned the relationship between infectious agents, inflammation and dilated cardiomyopathy (DCM). Objectives: The aim of this study was to determine the frequency of infectious agents and inflammation in endomyocardial biopsy (EMB) specimens from patients with idiopathic DCM, explanted hearts from different etiologies, including Chagas' disease, compared to donated hearts. Methods: From 2008 to 2011, myocardial samples from 29 heart donors and 55 patients with DCMs from different etiologies were studied (32 idiopathic, 9 chagasic, 6 ischemic and 8 other specific etiologies). Inflammation was investigated by immunohistochemistry and infectious agents by immunohistochemistry, molecular biology, in situ hybridization and electron microscopy. Results: There were no differences regarding the presence of macrophages, expression of HLA class II and ICAM-I in donors and DCM. Inflammation in Chagas' disease was predominant. By immunohistochemistry, in donors, there was a higher expression of antigens of enterovirus and Borrelia, hepatitis B and C in DCMs. By molecular biology, in all groups, the positivity was elevated to microorganisms, including co-infections, with a higher positivity to adenovirus and HHV6 in donors towards DCMs. This study was the first to demonstrate the presence of virus in the heart tissue of chagasic DCM. Conclusions: The presence of inflammation and infectious agents is frequent in donated hearts, in the myocardium of patients with idiopathic DCM, myocardial dysfunction related to cardiovascular diseases, and primary and secondary cardiomyopathies, including Chagas' disease. The role of co-infection in Chagas' heart disease physiopathology deserves to be investigated in future studies.