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- W2597183429 abstract "Rationale: Nuclear receptor Nur77, also known as NR4A1, TR3 or NGFI-B, is expressed in human atherosclerotic lesions in macrophages, endothelial cells, T cells and smooth muscle cells. Macrophages play a critical role in atherosclerosis and the function of Nur77 in lesion macrophages has not yet been investigated. Objective: This study aims to delineate the function of Nur77 in macrophages and to assess the effect of bone marrow-specific deficiency of Nur77 on atherosclerosis. Methods and results: We investigated Nur77 in macrophage polarization using bone marrow-derived macrophages (BMM) from wild-type and Nur77-knockout (Nur77 -/- )-mice (n=10). Nur77 -/- BMM exhibit changed expression of M2-specific markers and an inflammatory M1-phenotype with enhanced expression of IL12, IFNγ, and SDF-1α and increased NO synthesis in (non)-stimulated Nur77 -/- BMM cells. SDF-1α expression in non-stimulated Nur77 -/- BMM is repressed by Nur77 and the chemoattractive activity of Nur77 -/- BMM is abolished by SDF-1α inhibiting antibodies. Furthermore, Nur77 -/- mice show enhanced thioglycollate-elicited migration of macrophages and B-cells. The effect of bone marrow-specific deficiency of Nur77 on atherosclerosis was studied in low density lipoprotein receptor-deficient (Ldlr -/- ) mice. Ldlr -/- mice with a Nur77 -/- -deficient bone marrow transplant develop 2.1-fold larger atherosclerotic lesions than wild-type bone marrow transplanted mice. These lesions contain more macrophages, T cells, smooth muscle cells and larger necrotic cores. SDF-1α expression is higher in lesions of Nur77 -/- -transplanted mice, which may explain the observed aggravation of lesion formation. Conclusions: In conclusion, in bone-marrow derived cells the nuclear receptor Nur77 has an anti-inflammatory function, represses SDF-1α expression and inhibits atherosclerosis." @default.
- W2597183429 created "2017-03-23" @default.
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- W2597183429 date "2012-05-01" @default.
- W2597183429 modified "2023-09-26" @default.
- W2597183429 title "Abstract 471: Nuclear Receptor Nur77 Reduces Atherosclerosis" @default.
- W2597183429 doi "https://doi.org/10.1161/atvb.32.suppl_1.a471" @default.
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