Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8579
Title: Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells.
Authors: Soares, Milena Botelho Pereira
Lima, Ricardo Santana de
Souza, Bruno Solano de Freitas
Vasconcelos, Juliana Fraga
Rocha, Leonardo Lima
Santos, Ricardo Ribeiro dos
Iacobas, Sanda
Goldenberg, Regina Coeli dos Santos
Lisanti, Michael P
Iacobas, Dumitru Andrei
Tanowitz, Herbert Bernard
Spray, David Conover
Carvalho, Antonio Carlos Campos de
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brasil
Universidade Federal do Vale do São Francisco. Departamento de Medicina. Petrolina, PE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brasil
Albert Einstein College of Medicine. Dominick P. Purpura Department of Neuroscience. Bronx, NY, USA
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil
Thomas Jefferson University. Department of Stem Cell Biology and Regenerative Medicine. Kimmel Cancer Center. Philadelphia, PA, USA
Albert Einstein College of Medicine. Dominick P. Purpura Department of Neuroscience. Bronx, NY, USA
Albert Einstein College of Medicine. Department of Medicine. Bronx, NY, USA / Albert Einstein College of Medicine. Department of Pathology. Bronx, NY, USA
Albert Einstein College of Medicine. Dominick P. Purpura Department of Neuroscience. Bronx, NY, USA / Albert Einstein College of Medicine. Department of Medicine. Bronx, NY, USA
Albert Einstein College of Medicine. Dominick P. Purpura Department of Neuroscience. Bronx, NY, USA / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / 8Instituto Nacional de Cardiologia. Rio de Janeiro, RJ, Brasil
Abstract: Chronic chagasic cardiomyopathy is a leading cause of heart failure in Latin American countries, being associated with intense inflammatory response and fibrosis. We have previously shown that bone marrow mononuclear cell (BMC) transplantation improves inflammation, fibrosis, and ventricular diameter in hearts of mice with chronic Chagas disease. Here we investigated the transcriptomic recovery induced by BMC therapy by comparing the heart transcriptomes of control, chagasic, and BMC transplanted mice. Out of the 9390 unique genes quantified in all samples, 1702 had their expression altered in chronic chagasic hearts compared to those of normal mice. Major categories of significantly upregulated genes were related to inflammation, fibrosis and immune responses, while genes involved in mitochondrion function were downregulated. When BMC-treated chagasic hearts were compared to infected mice, 96% of the alterations detected in infected hearts were restored to normal levels, although an additional 109 genes were altered by treatment. Transcriptomic recovery, a new measure that considers both resotrative and side effects of treatment, was remarkably high (84%). Immunofluorescence and morphometric analyses confirmed the effects of BMC therapy in the pattern of inflammatory-immune response and expression of adhesion molecules. In conclusion, by using large-scale gene profiling for unbiased assessment of therapeutic efficacy we demonstrate immunomodulatory effects of BMC therapy in chronic chagasic cardiomyopathy and identify potentially relevant factors involved in the pathogenesis of the disease that may provide new therapeutic targets
Keywords: Chagas disease
Trypanosoma cruzi
Cardiomyopathy
Cell transplantation
Microarray
Inflammation
Fibrosis
DeCS: Transplante de Medula Óssea/patologia
Cardiomiopatia Chagásica/genética
Regulação da Expressão Gênica/imunologia
Miocárdio/imunologia
Trypanosoma cruzi/imunologia
Animais
Transplante de Medula Óssea/imunologia
Cardiomiopatia Chagásica/imunologia
Cardiomiopatia Chagásica/terapia
Doença Crônica
Modelos Animais de Doenças
Feminino
Fibrose
Galectina 3/genética
Perfilação da Expressão Gênica/métodos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Miocárdio/metabolismo
Análise de Sequência com Séries de Oligonucleotídeos
Trypanosoma cruzi/classificação
Fator de von Willebrand/genética
Issue Date: 2011
Publisher: Landes Bioscience
Citation: SOARES, M. B. P. et al. Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells. Cell Cycle, v. 10, n. 9, p. 1448-1455, 2011.
DOI: 10.4161/cc.10.9.15487
ISSN: 1551-4005
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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