Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice
IgG Fc receptors (FcγRs) play a role in activating the immune system and in maintaining peripheral tolerance, but their role in atherosclerosis is unknown. We generated double-knockout (DKO) mice by crossing apolipoprotein E–deficient mice (apoE−/−) with FcγR γ chain–deficient mice (γ−/−). The size...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión enviada para evaluación y publicación |
| Fecha de publicación: | 2006 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/378095 |
| Acceso en línea: | http://hdl.handle.net/10261/378095 |
| Access Level: | acceso abierto |
| Palabra clave: | Fc receptors Atherosclerosis Double-knockout mice Immune complexes |
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Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout MiceHernández-Vargas, PurificaciónOrtiz-Muñoz, GuadalupeLópez-Franco, OscarSuzuki, YusukeGallego-Delgado, JulioSanjuán, GuillermoLázaro, AlbertoLópez-Parra, VirginiaOrtega, LuisEgido, JesúsGómez-Guerrero, CarmenFc receptorsAtherosclerosisDouble-knockout miceImmune complexesIgG Fc receptors (FcγRs) play a role in activating the immune system and in maintaining peripheral tolerance, but their role in atherosclerosis is unknown. We generated double-knockout (DKO) mice by crossing apolipoprotein E–deficient mice (apoE−/−) with FcγR γ chain–deficient mice (γ−/−). The size of atherosclerotic lesions along the aorta was approximately 50% lower in DKO compared with apoE−/− control mice, without differences in serum lipid levels. The macrophage and T-cell content of lesions in the DKO were reduced by 49±6% and 56±8%, respectively, compared with the content in apoE−/− lesions. Furthermore, the expression of monocyte chemoattractant protein-1 (MCP-1), RANTES (Regulated on Activated Normal T-cell Expressed and Secreted), and intercellular adhesion molecule-1 (ICAM-1) and the activation of nuclear factor-κB (NF-κB) were significantly reduced in aortic lesions from DKO mice. In vitro, vascular smooth muscle cells (VSMCs) from both γ−/− and DKO mice failed to respond to immune complexes, as shown by impaired chemokine expression and NF-κB activation. ApoE−/− mice have higher levels of activating FcγRI and FcγRIIIA, and inhibitory FcγRIIB, compared with wild-type mice. The DKO mice express only the inhibitory FcγRIIB receptor. We conclude that FcγR deficiency limits development and progression of atherosclerosis. In addition to leukocytes, FcγR activation in VSMCs contributes to the inflammatory process, in part, by regulating chemokine expression and leukocyte invasion of the vessel wall. These results underscore the critical role of FcγRs in atherogenesis and support the use of immunotherapy in the treatment of this disease.This work was supported by grants from the Fondo de Investigacion Sanitaria (PI02/0539), Comunidad Autónoma de Madrid (GR/SAL/0411/2004), Ministerio de Educación y Cultura (2005/05857; and Ramon y Cajal Program to C.G.-G.), and Mutua Madrileña. G.O.-M. and V.L.-P. are fellows from Fondo de Investigacion Sanitaria and Comunidad Autónoma de Madrid, respectively.NoAmerican Heart AssociationComunidad de MadridMinisterio de Educación y Cultura (España)Fundación Mutua Madrileña202520252006info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Preprintinfo:eu-repo/semantics/submittedVersionapplication/pdfhttp://hdl.handle.net/10261/378095reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1161/01.RES.0000250556.07796.6cNoinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3780952026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice |
| title |
Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice |
| spellingShingle |
Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice Hernández-Vargas, Purificación Fc receptors Atherosclerosis Double-knockout mice Immune complexes |
| title_short |
Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice |
| title_full |
Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice |
| title_fullStr |
Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice |
| title_full_unstemmed |
Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice |
| title_sort |
Fcγ Receptor Deficiency Confers Protection Against Atherosclerosis in Apolipoprotein E Knockout Mice |
| dc.creator.none.fl_str_mv |
Hernández-Vargas, Purificación Ortiz-Muñoz, Guadalupe López-Franco, Oscar Suzuki, Yusuke Gallego-Delgado, Julio Sanjuán, Guillermo Lázaro, Alberto López-Parra, Virginia Ortega, Luis Egido, Jesús Gómez-Guerrero, Carmen |
| author |
Hernández-Vargas, Purificación |
| author_facet |
Hernández-Vargas, Purificación Ortiz-Muñoz, Guadalupe López-Franco, Oscar Suzuki, Yusuke Gallego-Delgado, Julio Sanjuán, Guillermo Lázaro, Alberto López-Parra, Virginia Ortega, Luis Egido, Jesús Gómez-Guerrero, Carmen |
| author_role |
author |
| author2 |
Ortiz-Muñoz, Guadalupe López-Franco, Oscar Suzuki, Yusuke Gallego-Delgado, Julio Sanjuán, Guillermo Lázaro, Alberto López-Parra, Virginia Ortega, Luis Egido, Jesús Gómez-Guerrero, Carmen |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Comunidad de Madrid Ministerio de Educación y Cultura (España) Fundación Mutua Madrileña |
| dc.subject.none.fl_str_mv |
Fc receptors Atherosclerosis Double-knockout mice Immune complexes |
| topic |
Fc receptors Atherosclerosis Double-knockout mice Immune complexes |
| description |
IgG Fc receptors (FcγRs) play a role in activating the immune system and in maintaining peripheral tolerance, but their role in atherosclerosis is unknown. We generated double-knockout (DKO) mice by crossing apolipoprotein E–deficient mice (apoE−/−) with FcγR γ chain–deficient mice (γ−/−). The size of atherosclerotic lesions along the aorta was approximately 50% lower in DKO compared with apoE−/− control mice, without differences in serum lipid levels. The macrophage and T-cell content of lesions in the DKO were reduced by 49±6% and 56±8%, respectively, compared with the content in apoE−/− lesions. Furthermore, the expression of monocyte chemoattractant protein-1 (MCP-1), RANTES (Regulated on Activated Normal T-cell Expressed and Secreted), and intercellular adhesion molecule-1 (ICAM-1) and the activation of nuclear factor-κB (NF-κB) were significantly reduced in aortic lesions from DKO mice. In vitro, vascular smooth muscle cells (VSMCs) from both γ−/− and DKO mice failed to respond to immune complexes, as shown by impaired chemokine expression and NF-κB activation. ApoE−/− mice have higher levels of activating FcγRI and FcγRIIIA, and inhibitory FcγRIIB, compared with wild-type mice. The DKO mice express only the inhibitory FcγRIIB receptor. We conclude that FcγR deficiency limits development and progression of atherosclerosis. In addition to leukocytes, FcγR activation in VSMCs contributes to the inflammatory process, in part, by regulating chemokine expression and leukocyte invasion of the vessel wall. These results underscore the critical role of FcγRs in atherogenesis and support the use of immunotherapy in the treatment of this disease. |
| publishDate |
2006 |
| dc.date.none.fl_str_mv |
2006 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Preprint info:eu-repo/semantics/submittedVersion |
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article |
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submittedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/378095 |
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http://hdl.handle.net/10261/378095 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
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https://doi.org/10.1161/01.RES.0000250556.07796.6c No |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
American Heart Association |
| publisher.none.fl_str_mv |
American Heart Association |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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