CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice
Por:
Gutiérrez-Muñoz C., Méndez-Barbero N., Svendsen P., Sastre C., Fernández-Laso V., Quesada P., Egido J., Escolá-Gil J.C., Martín-Ventura J.L., Moestrup S.K., Blanco-Colio L.M.
Publicada:
1 ene 2020
Ahead of Print:
1 sep 2020
Resumen:
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. © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology
Filiaciones:
Gutiérrez-Muñoz C.:
Vascular Research Laboratory, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain
Méndez-Barbero N.:
Vascular Research Laboratory, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Svendsen P.:
Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Sastre C.:
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
Fernández-Laso V.:
Vascular Research Laboratory, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Quesada P.:
Vascular Research Laboratory, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain
Egido J.:
Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Madrid, Spain
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas (CIBERDEM), Madrid, Spain
Escolá-Gil J.C.:
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas (CIBERDEM), Madrid, Spain
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
Martín-Ventura J.L.:
Vascular Research Laboratory, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Moestrup S.K.:
Department of Molecular Medicine, University of Southern Denmark, Oddense, Denmark
Department of Biomedicine, Aarhus University, Aarhus, Denmark
Blanco-Colio L.M.:
Vascular Research Laboratory, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
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