Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Feb 3;110(3):428-38.
doi: 10.1161/CIRCRESAHA.111.260760. Epub 2011 Dec 22.

Bone marrow-specific deficiency of nuclear receptor Nur77 enhances atherosclerosis

Affiliations

Bone marrow-specific deficiency of nuclear receptor Nur77 enhances atherosclerosis

Anouk A J Hamers et al. Circ Res. .

Erratum in

  • Circ Res. 2012 Mar 2;110(5):e46. Marincovic, Goran [corrected to Marinković, Goran]

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. Nur77(-/-) BMM exhibit changed expression of M2-specific markers and an inflammatory M1-phenotype with enhanced expression of interleukin-12, IFNγ, and SDF-1α and increased NO synthesis in (non)-stimulated Nur77(-/-) BMM cells. SDF-1α expression in nonstimulated 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 developed 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.

PubMed Disclaimer

Comment in

Similar articles

Cited by

Publication types

MeSH terms

LinkOut - more resources