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

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DOI

  • Carmen Gutiérrez-Muñoz, Universidad Autónoma de Madrid
  • ,
  • Nerea Méndez-Barbero, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
  • ,
  • Pia Svendsen
  • Cristina Sastre, Harvard University
  • ,
  • Valvanera Fernández-Laso, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
  • ,
  • Patricia Quesada, Universidad Autónoma de Madrid
  • ,
  • Jesús Egido, Universidad Autónoma de Madrid, CIBER - Center for Biomedical Research Network
  • ,
  • Joan C. Escolá-Gil, CIBER - Center for Biomedical Research Network, CSIC - Institute of Biomedical Research of Barcelona
  • ,
  • Jose L. Martín-Ventura, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
  • ,
  • Soren K. Moestrup
  • Luis M. Blanco-Colio, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)

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.

Original languageEnglish
JournalFASEB Journal
Volume34
Issue11
Pages (from-to)14960-14976
Number of pages17
ISSN0892-6638
DOIs
Publication statusPublished - Nov 2020

    Research areas

  • atherosclerosis, CD163, inflammation, TWEAK

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