Molecular Medicine

, Volume 17, Issue 9–10, pp 1056–1064 | Cite as

Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE−/− and LDLR−/− Mice

  • Oleg Bogachev
  • Amin Majdalawieh
  • Xuefang Pan
  • Lei Zhang
  • Hyo-Sung Ro
Research Article


Atherogenesis is a long-term process that involves inflammatory response coupled with metabolic dysfunction. Foam cell formation and macrophage inflammatory response are two key events in atherogenesis. Adipocyte enhancer-binding protein 1 (AEBP1) has been shown to impede macrophage cholesterol efflux, promoting foam cell formation, via peroxisome proliferator-activated receptor (PPAR)-γl and liver X receptor α (LXRα) downregulation. Moreover, AEBP1 has been shown to promote macrophage inflammatory responsiveness by inducing nuclear factor (NF)-κB activity via IκBα downregulation. Lipopolysaccharide (LPS)-induced suppression of pivotal macrophage cholesterol efflux mediators, leading to foam cell formation, has been shown to be mediated by AEBP1. Herein, we showed that AEBP1-transgenic mice (AEBP1TG) with macrophage-specific AEBP1 overexpression exhibit hyperlipidemia and develop atherosclerotic lesions in their proximal aortas. Consistently, ablation of AEBP1 results in significant attenuation of atherosclerosis (males: 3.2-fold, P = 0.001 (en face)), 2.7-fold, P = 0.0004 (aortic roots); females: 2.1-fold, P = 0.0026 (en face), 1.7-fold, P = 0.0126 (aortic roots)) in the AEBP1−/−/low-density lipoprotein receptor (LDLR)−/− double-knockout (KO) mice. Bone marrow (BM) transplantation experiments further revealed that LDLR−/− mice reconstituted with AEBP1−/−/LDLR−/− BM cells (LDLR−/−/KO-BM chimera) display significant reduction of atherosclerosis lesions (en face: 2.0-fold, P = 0.0268; aortic roots: 1.7-fold, P = 0.05) compared with control mice reconstituted with AEBP1+/+/LDLR−/− BM cells (LDLR−/−/WT-BM chimera). Furthermore, transplantation of AEBP1TG BM cells with the normal apolipoprotein E (ApoE) gene into ApoE−/− mice (ApoE−/−/TG-BM chimera) leads to significant development of atherosclerosis (males: 2.5-fold, P = 0.0001 (en face), 4.7-fold, P = 0.0001 [aortic roots]; females: 1.8-fold, P = 0.0001 (en face), 3.0-fold, P = 0.0001 [aortic roots]) despite the restoration of ApoE expression. Macrophages from ApoE−/−/TG-BM chimeric mice express reduced levels of PPARγ1, LXRα, ATP-binding cassette A1 (ABCA1) and ATP-binding cassette G1 (ABCG1) and increased levels of the inflammatory mediators interleukin (IL)-6 and tumor necrosis factor (TNF)-α compared with macrophages of control chimeric mice (ApoE−/−/NT-BM) that received AEBP1 nontransgenic (AEBP1NT) BM cells. Our in vivo experimental data strongly suggest that macrophage AEBP1 plays critical regulatory roles in atherogenesis, and it may serve as a potential therapeutic target for the prevention or treatment of atherosclerosis.



We thank Chris Webber, Janette Flemming, Debby Currie and Patricia Colp for their technical assistance. This work was supported by a grant from the Canadian Institutes of Health Research (to H-S Ro).

Supplementary material

10020_2011_1791056_MOESM1_ESM.pdf (274 kb)
Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE−/− and LDLR−/− Mice


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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Oleg Bogachev
    • 1
  • Amin Majdalawieh
    • 1
  • Xuefang Pan
    • 1
  • Lei Zhang
    • 1
  • Hyo-Sung Ro
    • 1
  1. 1.Department of Biochemistry and Molecular Biology, Faculty of MedicineDalhousie UniversityHalifaxCanada

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