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...
| Authors: | , , , , , , , , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2020 |
| Country: | España |
| Institution: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repository: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p10231 |
| Online Access: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10231 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85090954500&doi=10.1096%2ffj.202000177R&partnerID=40&md5=5f3202c1fe95e80d929fca5016c23df0 |
| Access Level: | Open access |
| Keyword: | apolipoprotein E CD163 antigen cholesterol high density lipoprotein cholesterol immunoglobulin enhancer binding protein metalloproteinase recombinant antigen triacylglycerol tumor necrosis factor ligand superfamily member 12 cell surface receptor cytokine differentiation antigen leukocyte antigen Tnfsf12 protein, mouse animal cell animal experiment animal model animal tissue Article atherosclerotic plaque cell migration cholesterol blood level controlled study disease course female foam cell in vitro study mouse nonhuman peritoneum macrophage phenotype priority journal protein expression RAW 264.7 cell line triacylglycerol blood level upregulation vascular smooth muscle cell animal apolipoprotein E knockout mouse atherosclerosis C57BL mouse knockout mouse macrophage male metabolism pathology physiology Animals Antigens, CD Antigens, Diff |
| Summary: | 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 |
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