Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium
- Autores
- González, Mariela Natacha; Dey, Nilay; Garg, Nisha J.; Postan, Miriam
- Año de publicación
- 2013
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background: The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization,ameliorates T. cruzi-induced myocarditis. Methods and results: T. cruzi-infected C3H/He mice were treated with G-CSF and monitored for parasite burden,BMSC mobilization, cytokine profile and cardiac remodeling. G-CSF increased the expression of CXCR4, CD34, and c-Kit, indicatingmobilization and migration of BMSC, some of which differentiated to cardiomyocytes as evidenced by increased levels of GATA4+/MEF2C+ cells and desmin expression in chagasic hearts. G-CSF enhanced amixed cytokine response (IL-10 + TGF-β > IFN-γ + TNF-α > IL-4) associated with increased heart inflammation and no beneficial effect on parasite control. Further, G-CSF controlled T. cruzi-induced extracellular-matrix alterations of collagens (Col I and Col llI), hydroxyproline, and glycosaminoglycan contents and promoted compensatory cardiac remodeling; however, these responses were not sufficient to control T. cruzi-induced cardiomyocyte atrophy. Benznidazole treatment prior to G-CSF resulted in the control of parasitism and parasite-induced inflammation, and subsequently, G-CSF was effective in executing the tissue repair, as evidenced by extracellular-matrix homeostasis and normalization of cardiomyocyte size in chagasic hearts. Conclusions: G-CSF treatment after T. cruzi infection enhanced migration and homing of BMSC, some of which differentiated to cardiomyocytes. Yet, G-CSF promoted a mixed (Treg > Th1 > Th2) immune response that contributed to persistent inflammation and limited improvement in cardiac homeostasis. Combinatorial therapy (BZ → G-CSF) was beneficial in arresting inflammatory processes and tissue damage in chagasic hearts.
Fil: González, Mariela Natacha. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina
Fil: Dey, Nilay. University of Texas Medical Branch. Departments of Microbiology and Immunology and Pathology; Estados Unidos
Fil: Garg, Nisha J.. University of Texas Medical Branch. Departments of Microbiology and Immunology and Pathology; Estados Unidos
Fil: Postan, Miriam. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina - Materia
-
Trypanosoma cruzi
Granulocyte-colony stimulating factor
Stem cell
Cardiac repair
Chagas disease - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/24595
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/24595 |
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3498 |
network_name_str |
CONICET Digital (CONICET) |
spelling |
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardiumGonzález, Mariela NatachaDey, NilayGarg, Nisha J.Postan, MiriamTrypanosoma cruziGranulocyte-colony stimulating factorStem cellCardiac repairChagas diseasehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization,ameliorates T. cruzi-induced myocarditis. Methods and results: T. cruzi-infected C3H/He mice were treated with G-CSF and monitored for parasite burden,BMSC mobilization, cytokine profile and cardiac remodeling. G-CSF increased the expression of CXCR4, CD34, and c-Kit, indicatingmobilization and migration of BMSC, some of which differentiated to cardiomyocytes as evidenced by increased levels of GATA4+/MEF2C+ cells and desmin expression in chagasic hearts. G-CSF enhanced amixed cytokine response (IL-10 + TGF-β > IFN-γ + TNF-α > IL-4) associated with increased heart inflammation and no beneficial effect on parasite control. Further, G-CSF controlled T. cruzi-induced extracellular-matrix alterations of collagens (Col I and Col llI), hydroxyproline, and glycosaminoglycan contents and promoted compensatory cardiac remodeling; however, these responses were not sufficient to control T. cruzi-induced cardiomyocyte atrophy. Benznidazole treatment prior to G-CSF resulted in the control of parasitism and parasite-induced inflammation, and subsequently, G-CSF was effective in executing the tissue repair, as evidenced by extracellular-matrix homeostasis and normalization of cardiomyocyte size in chagasic hearts. Conclusions: G-CSF treatment after T. cruzi infection enhanced migration and homing of BMSC, some of which differentiated to cardiomyocytes. Yet, G-CSF promoted a mixed (Treg > Th1 > Th2) immune response that contributed to persistent inflammation and limited improvement in cardiac homeostasis. Combinatorial therapy (BZ → G-CSF) was beneficial in arresting inflammatory processes and tissue damage in chagasic hearts.Fil: González, Mariela Natacha. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Dey, Nilay. University of Texas Medical Branch. Departments of Microbiology and Immunology and Pathology; Estados UnidosFil: Garg, Nisha J.. University of Texas Medical Branch. Departments of Microbiology and Immunology and Pathology; Estados UnidosFil: Postan, Miriam. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaElsevier Ireland2013-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24595González, Mariela Natacha; Dey, Nilay; Garg, Nisha J.; Postan, Miriam; Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium; Elsevier Ireland; International Journal of Cardiology; 168; 3; 4-2013; 2567-25740167-5273CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0167527313004683info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijcard.2013.03.049info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797178/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:35Zoai:ri.conicet.gov.ar:11336/24595instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:36.184CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium |
title |
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium |
spellingShingle |
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium González, Mariela Natacha Trypanosoma cruzi Granulocyte-colony stimulating factor Stem cell Cardiac repair Chagas disease |
title_short |
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium |
title_full |
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium |
title_fullStr |
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium |
title_full_unstemmed |
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium |
title_sort |
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium |
dc.creator.none.fl_str_mv |
González, Mariela Natacha Dey, Nilay Garg, Nisha J. Postan, Miriam |
author |
González, Mariela Natacha |
author_facet |
González, Mariela Natacha Dey, Nilay Garg, Nisha J. Postan, Miriam |
author_role |
author |
author2 |
Dey, Nilay Garg, Nisha J. Postan, Miriam |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
Trypanosoma cruzi Granulocyte-colony stimulating factor Stem cell Cardiac repair Chagas disease |
topic |
Trypanosoma cruzi Granulocyte-colony stimulating factor Stem cell Cardiac repair Chagas disease |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Background: The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization,ameliorates T. cruzi-induced myocarditis. Methods and results: T. cruzi-infected C3H/He mice were treated with G-CSF and monitored for parasite burden,BMSC mobilization, cytokine profile and cardiac remodeling. G-CSF increased the expression of CXCR4, CD34, and c-Kit, indicatingmobilization and migration of BMSC, some of which differentiated to cardiomyocytes as evidenced by increased levels of GATA4+/MEF2C+ cells and desmin expression in chagasic hearts. G-CSF enhanced amixed cytokine response (IL-10 + TGF-β > IFN-γ + TNF-α > IL-4) associated with increased heart inflammation and no beneficial effect on parasite control. Further, G-CSF controlled T. cruzi-induced extracellular-matrix alterations of collagens (Col I and Col llI), hydroxyproline, and glycosaminoglycan contents and promoted compensatory cardiac remodeling; however, these responses were not sufficient to control T. cruzi-induced cardiomyocyte atrophy. Benznidazole treatment prior to G-CSF resulted in the control of parasitism and parasite-induced inflammation, and subsequently, G-CSF was effective in executing the tissue repair, as evidenced by extracellular-matrix homeostasis and normalization of cardiomyocyte size in chagasic hearts. Conclusions: G-CSF treatment after T. cruzi infection enhanced migration and homing of BMSC, some of which differentiated to cardiomyocytes. Yet, G-CSF promoted a mixed (Treg > Th1 > Th2) immune response that contributed to persistent inflammation and limited improvement in cardiac homeostasis. Combinatorial therapy (BZ → G-CSF) was beneficial in arresting inflammatory processes and tissue damage in chagasic hearts. Fil: González, Mariela Natacha. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina Fil: Dey, Nilay. University of Texas Medical Branch. Departments of Microbiology and Immunology and Pathology; Estados Unidos Fil: Garg, Nisha J.. University of Texas Medical Branch. Departments of Microbiology and Immunology and Pathology; Estados Unidos Fil: Postan, Miriam. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina |
description |
Background: The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization,ameliorates T. cruzi-induced myocarditis. Methods and results: T. cruzi-infected C3H/He mice were treated with G-CSF and monitored for parasite burden,BMSC mobilization, cytokine profile and cardiac remodeling. G-CSF increased the expression of CXCR4, CD34, and c-Kit, indicatingmobilization and migration of BMSC, some of which differentiated to cardiomyocytes as evidenced by increased levels of GATA4+/MEF2C+ cells and desmin expression in chagasic hearts. G-CSF enhanced amixed cytokine response (IL-10 + TGF-β > IFN-γ + TNF-α > IL-4) associated with increased heart inflammation and no beneficial effect on parasite control. Further, G-CSF controlled T. cruzi-induced extracellular-matrix alterations of collagens (Col I and Col llI), hydroxyproline, and glycosaminoglycan contents and promoted compensatory cardiac remodeling; however, these responses were not sufficient to control T. cruzi-induced cardiomyocyte atrophy. Benznidazole treatment prior to G-CSF resulted in the control of parasitism and parasite-induced inflammation, and subsequently, G-CSF was effective in executing the tissue repair, as evidenced by extracellular-matrix homeostasis and normalization of cardiomyocyte size in chagasic hearts. Conclusions: G-CSF treatment after T. cruzi infection enhanced migration and homing of BMSC, some of which differentiated to cardiomyocytes. Yet, G-CSF promoted a mixed (Treg > Th1 > Th2) immune response that contributed to persistent inflammation and limited improvement in cardiac homeostasis. Combinatorial therapy (BZ → G-CSF) was beneficial in arresting inflammatory processes and tissue damage in chagasic hearts. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-04 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/24595 González, Mariela Natacha; Dey, Nilay; Garg, Nisha J.; Postan, Miriam; Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium; Elsevier Ireland; International Journal of Cardiology; 168; 3; 4-2013; 2567-2574 0167-5273 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/24595 |
identifier_str_mv |
González, Mariela Natacha; Dey, Nilay; Garg, Nisha J.; Postan, Miriam; Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium; Elsevier Ireland; International Journal of Cardiology; 168; 3; 4-2013; 2567-2574 0167-5273 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0167527313004683 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijcard.2013.03.049 info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797178/ |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier Ireland |
publisher.none.fl_str_mv |
Elsevier Ireland |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842270051404611584 |
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13.13397 |