| First Author | Gutiérrez-Muñoz C | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 11 | Pages | 14960-14976 |
| PubMed ID | 32924185 | Mgi Jnum | J:306005 |
| Mgi Id | MGI:6708496 | Doi | 10.1096/fj.202000177R |
| Citation | Gutierrez-Munoz C, et al. (2020) CD163 deficiency increases foam cell formation and plaque progression in atherosclerotic mice. FASEB J 34(11):14960-14976 |
| abstractText | 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. |
