Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells.

dc.creatorSoares, Milena Botelho Pereira
dc.creatorLima, Ricardo Santana de
dc.creatorSouza, Bruno Solano de Freitas
dc.creatorVasconcelos, Juliana Fraga
dc.creatorRocha, Leonardo Lima
dc.creatorSantos, Ricardo Ribeiro dos
dc.creatorIacobas, Sanda
dc.creatorGoldenberg, Regina Coeli dos Santos
dc.creatorLisanti, Michael P
dc.creatorIacobas, Dumitru Andrei
dc.creatorTanowitz, Herbert Bernard
dc.creatorSpray, David Conover
dc.creatorCarvalho, Antonio Carlos Campos de
dc.date2014-10-13T17:55:09Z
dc.date2014-10-13T17:55:09Z
dc.date2011
dc.date.accessioned2023-09-26T20:09:26Z
dc.date.available2023-09-26T20:09:26Z
dc.identifierSOARES, 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.
dc.identifier1551-4005
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/8579
dc.identifier10.4161/cc.10.9.15487
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8849957
dc.descriptionChronic 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
dc.formatapplication/pdf
dc.languageeng
dc.publisherLandes Bioscience
dc.rightsopen access
dc.subjectChagas disease
dc.subjectTrypanosoma cruzi
dc.subjectCardiomyopathy
dc.subjectCell transplantation
dc.subjectMicroarray
dc.subjectInflammation
dc.subjectFibrosis
dc.subjectTransplante de Medula Óssea/patologia
dc.subjectCardiomiopatia Chagásica/genética
dc.subjectRegulação da Expressão Gênica/imunologia
dc.subjectMiocárdio/imunologia
dc.subjectTrypanosoma cruzi/imunologia
dc.subjectAnimais
dc.subjectTransplante de Medula Óssea/imunologia
dc.subjectCardiomiopatia Chagásica/imunologia
dc.subjectCardiomiopatia Chagásica/terapia
dc.subjectDoença Crônica
dc.subjectModelos Animais de Doenças
dc.subjectFeminino
dc.subjectFibrose
dc.subjectGalectina 3/genética
dc.subjectPerfilação da Expressão Gênica/métodos
dc.subjectMasculino
dc.subjectCamundongos
dc.subjectCamundongos Endogâmicos C57BL
dc.subjectMiocárdio/metabolismo
dc.subjectAnálise de Sequência com Séries de Oligonucleotídeos
dc.subjectTrypanosoma cruzi/classificação
dc.subjectFator de von Willebrand/genética
dc.titleReversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells.
dc.typeArticle


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