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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24595
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/24595
network_acronym_str CONICETDig
repository_id_str 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 Técnicas2025-09-29T10:37:34Zoai: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:34982025-09-29 10:37:34.995CONICET 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
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv 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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