Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response

Detalhes bibliográficos
Autor(a) principal: Pereira, Isabela Resende
Data de Publicação: 2015
Outros Autores: Pereira, Glaucia Villar, Moreira, Otacílio Cruz, Ramos, Isalira Peroba, Gibaldi, Daniel, Britto, Constança, Moraes, Milton Ozório, Lannes-Vieira, Joseli
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/14012
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
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spelling Pereira, Isabela ResendePereira, Glaucia VillarMoreira, Otacílio CruzRamos, Isalira PerobaGibaldi, DanielBritto, ConstançaMoraes, Milton OzórioLannes-Vieira, Joseli2016-04-28T15:07:54Z2016-04-28T15:07:54Z2015PEREIRA, Isabela Resende; et al. Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response. Plos One, v.9, n.3, e0003659, 23p, Mar. 2015.1932-6203https://www.arca.fiocruz.br/handle/icict/1401210.1371/ journal.pntd.0003659engPublic Library of SciencePentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Responseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Cardiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.BACKGROUND: Chronic chagasic cardiomyopathy (CCC), the main clinical sign of Chagas disease, is associated with systemic CD8+ T-cell abnormalities and CD8-enriched myocarditis occurring in an inflammatory milieu. Pentoxifylline (PTX), a phosphodiesterase inhibitor, has immunoregulatory and cardioprotective properties. Here, we tested PTX effects on CD8+ T-cell abnormalities and cardiac alterations using a model of experimental Chagas' heart disease. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice chronically infected by the Colombian Trypanosoma cruzi strain and presenting signs of CCC were treated with PTX. The downmodulation of T-cell receptors on CD8+ cells induced by T. cruzi infection was rescued by PTX therapy. Also, PTX reduced the frequency of CD8+ T-cells expressing activation and migration markers in the spleen and the activation of blood vessel endothelial cells and the intensity of inflammation in the heart tissue. Although preserved interferon-gamma production systemically and in the cardiac tissue, PTX therapy reduced the number of perforin+ cells invading this tissue. PTX did not alter parasite load, but hampered the progression of heart injury, improving connexin 43 expression and decreasing fibronectin overdeposition. Further, PTX reversed electrical abnormalities as bradycardia and prolonged PR, QTc and QRS intervals in chronically infected mice. Moreover, PTX therapy improved heart remodeling since reduced left ventricular (LV) hypertrophy and restored the decreased LV ejection fraction. CONCLUSIONS/SIGNIFICANCE: PTX therapy ameliorates critical aspects of CCC and repositioned CD8+ T-cell response towards homeostasis, reinforcing that immunological abnormalities are crucially linked, as cause or effect, to CCC. Therefore, PTX emerges as a candidate to treat the non-beneficial immune deregulation associated with chronic Chagas' heart disease and to improve prognosis.Chagas diseaseChagasic cardiomyopathyPentoxifyllineCardiomiopatia ChagásicaDoença de ChagasPentoxifilinainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/14012/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALisabela_pereira_etal_IOC_2015.pdfisabela_pereira_etal_IOC_2015.pdfapplication/pdf6043084https://www.arca.fiocruz.br/bitstream/icict/14012/2/isabela_pereira_etal_IOC_2015.pdf03af83923a25cfd4e95c3be608b6e3b2MD52TEXTisabela_pereira_etal_IOC_2015.pdf.txtisabela_pereira_etal_IOC_2015.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response
title Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response
spellingShingle Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response
Pereira, Isabela Resende
Chagas disease
Chagasic cardiomyopathy
Pentoxifylline
Cardiomiopatia Chagásica
Doença de Chagas
Pentoxifilina
title_short Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response
title_full Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response
title_fullStr Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response
title_full_unstemmed Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response
title_sort Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response
author Pereira, Isabela Resende
author_facet Pereira, Isabela Resende
Pereira, Glaucia Villar
Moreira, Otacílio Cruz
Ramos, Isalira Peroba
Gibaldi, Daniel
Britto, Constança
Moraes, Milton Ozório
Lannes-Vieira, Joseli
author_role author
author2 Pereira, Glaucia Villar
Moreira, Otacílio Cruz
Ramos, Isalira Peroba
Gibaldi, Daniel
Britto, Constança
Moraes, Milton Ozório
Lannes-Vieira, Joseli
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Pereira, Isabela Resende
Pereira, Glaucia Villar
Moreira, Otacílio Cruz
Ramos, Isalira Peroba
Gibaldi, Daniel
Britto, Constança
Moraes, Milton Ozório
Lannes-Vieira, Joseli
dc.subject.en.pt_BR.fl_str_mv Chagas disease
Chagasic cardiomyopathy
Pentoxifylline
topic Chagas disease
Chagasic cardiomyopathy
Pentoxifylline
Cardiomiopatia Chagásica
Doença de Chagas
Pentoxifilina
dc.subject.decs.pt_BR.fl_str_mv Cardiomiopatia Chagásica
Doença de Chagas
Pentoxifilina
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
publishDate 2015
dc.date.issued.fl_str_mv 2015
dc.date.accessioned.fl_str_mv 2016-04-28T15:07:54Z
dc.date.available.fl_str_mv 2016-04-28T15:07:54Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv PEREIRA, Isabela Resende; et al. Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response. Plos One, v.9, n.3, e0003659, 23p, Mar. 2015.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/14012
dc.identifier.issn.none.fl_str_mv 1932-6203
dc.identifier.doi.none.fl_str_mv 10.1371/ journal.pntd.0003659
identifier_str_mv PEREIRA, Isabela Resende; et al. Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response. Plos One, v.9, n.3, e0003659, 23p, Mar. 2015.
1932-6203
10.1371/ journal.pntd.0003659
url https://www.arca.fiocruz.br/handle/icict/14012
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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