CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice

Atherosclerosis is an inflammatory disease characterized by the accumulation of macrophages in the vessel wall. Macrophages depend on their polarization to exert either pro-inflammatory or anti-inflammatory effects. Macrophages of the anti-inflammatory phenotype express high levels of CD163, a scave...

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Autores: Gutiérrez-Muñoz, Carmen, Méndez-Barbero, Nerea, Svendsen, Pia, Sastre, Cristina, Fernández-Laso, Valvanera, Quesada, Patricia, Egido, Jesús, Escolà-Gil, Joan Carles, Martín-Ventura, Jose Luis, Moestrup, Soren K., Blanco-Colio, Luis Miguel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/224123
Acceso en línea:http://hdl.handle.net/10261/224123
Access Level:acceso abierto
Palabra clave:Atherosclerosis
CD163
Inflammation
TWEA
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spelling CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic miceGutiérrez-Muñoz, CarmenMéndez-Barbero, NereaSvendsen, PiaSastre, CristinaFernández-Laso, ValvaneraQuesada, PatriciaEgido, JesúsEscolà-Gil, Joan CarlesMartín-Ventura, Jose LuisMoestrup, Soren K.Blanco-Colio, Luis MiguelAtherosclerosisCD163InflammationTWEAAtherosclerosis is an inflammatory disease characterized by the accumulation of macrophages in the vessel wall. Macrophages depend on their polarization to exert either pro-inflammatory or anti-inflammatory effects. Macrophages of the anti-inflammatory phenotype express high levels of CD163, a scavenger receptor for the hemoglobin-haptoglobin complex. CD163 can also bind to the pro-inflammatory cytokine TWEAK. Using ApoE-deficient or ApoE/CD163 double-deficient mice we aim to investigate the involvement of CD163 in atherosclerosis development and its capacity to neutralize the TWEAK actions. ApoE/CD163 double-deficient mice displayed a more unstable plaque phenotype characterized by an increased lipid and macrophage content, plaque size, and pro-inflammatory cytokine expression. In vitro experiments demonstrated that the absence of CD163 in M2-type macrophages-induced foam cell formation through upregulation of CD36 expression. Moreover, exogenous TWEAK administration increased atherosclerotic lesion size, lipids, and macrophages content in ApoE/CD163 compared with ApoE/CD163 mice. Treatment with recombinant CD163 was able to neutralize the proatherogenic effects of TWEAK in ApoE/CD163 double-deficient mice. Recombinant CD163 abolished the pro-inflammatory actions of TWEAK on vascular smooth muscle cells, decreasing NF-kB activation, cytokines and metalloproteinases expression, and macrophages migration. In conclusion, CD163-expressing macrophages serve as a protective mechanism to prevent the deleterious effects of TWEAK on atherosclerotic plaque development and progression.This work was supported by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (ISCiii/FEDER PI16/01419, PI19/00128) and Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) and Cardiovascular Disease (CIBERCV), SpainFederation of American Societies for Experimental BiologyMinisterio de Economía y Competitividad (España)Instituto de Salud Carlos IIIEuropean CommissionCentro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (España)Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/224123reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1096/fj.202000177RSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2241232026-05-22T06:33:51Z
dc.title.none.fl_str_mv CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice
title CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice
spellingShingle CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice
Gutiérrez-Muñoz, Carmen
Atherosclerosis
CD163
Inflammation
TWEA
title_short CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice
title_full CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice
title_fullStr CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice
title_full_unstemmed CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice
title_sort CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice
dc.creator.none.fl_str_mv Gutiérrez-Muñoz, Carmen
Méndez-Barbero, Nerea
Svendsen, Pia
Sastre, Cristina
Fernández-Laso, Valvanera
Quesada, Patricia
Egido, Jesús
Escolà-Gil, Joan Carles
Martín-Ventura, Jose Luis
Moestrup, Soren K.
Blanco-Colio, Luis Miguel
author Gutiérrez-Muñoz, Carmen
author_facet Gutiérrez-Muñoz, Carmen
Méndez-Barbero, Nerea
Svendsen, Pia
Sastre, Cristina
Fernández-Laso, Valvanera
Quesada, Patricia
Egido, Jesús
Escolà-Gil, Joan Carles
Martín-Ventura, Jose Luis
Moestrup, Soren K.
Blanco-Colio, Luis Miguel
author_role author
author2 Méndez-Barbero, Nerea
Svendsen, Pia
Sastre, Cristina
Fernández-Laso, Valvanera
Quesada, Patricia
Egido, Jesús
Escolà-Gil, Joan Carles
Martín-Ventura, Jose Luis
Moestrup, Soren K.
Blanco-Colio, Luis Miguel
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Instituto de Salud Carlos III
European Commission
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (España)
Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Atherosclerosis
CD163
Inflammation
TWEA
topic Atherosclerosis
CD163
Inflammation
TWEA
description Atherosclerosis is an inflammatory disease characterized by the accumulation of macrophages in the vessel wall. Macrophages depend on their polarization to exert either pro-inflammatory or anti-inflammatory effects. Macrophages of the anti-inflammatory phenotype express high levels of CD163, a scavenger receptor for the hemoglobin-haptoglobin complex. CD163 can also bind to the pro-inflammatory cytokine TWEAK. Using ApoE-deficient or ApoE/CD163 double-deficient mice we aim to investigate the involvement of CD163 in atherosclerosis development and its capacity to neutralize the TWEAK actions. ApoE/CD163 double-deficient mice displayed a more unstable plaque phenotype characterized by an increased lipid and macrophage content, plaque size, and pro-inflammatory cytokine expression. In vitro experiments demonstrated that the absence of CD163 in M2-type macrophages-induced foam cell formation through upregulation of CD36 expression. Moreover, exogenous TWEAK administration increased atherosclerotic lesion size, lipids, and macrophages content in ApoE/CD163 compared with ApoE/CD163 mice. Treatment with recombinant CD163 was able to neutralize the proatherogenic effects of TWEAK in ApoE/CD163 double-deficient mice. Recombinant CD163 abolished the pro-inflammatory actions of TWEAK on vascular smooth muscle cells, decreasing NF-kB activation, cytokines and metalloproteinases expression, and macrophages migration. In conclusion, CD163-expressing macrophages serve as a protective mechanism to prevent the deleterious effects of TWEAK on atherosclerotic plaque development and progression.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/224123
url http://hdl.handle.net/10261/224123
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1096/fj.202000177R
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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