Atherosclerosis is a chronic inflammatory disease. Leukocyte immunoglobulin-like receptor B4 (LILRB4) is associated with the pathological processes of various inflammatory diseases. However, the potential function and underlying mechanisms of LILRB4 in atherogenesis remain to be investigated. In the present study, LILRB4 expression was examined in both human and mouse atherosclerotic plaques. The effects and possible mechanisms of LILRB4 in atherogenesis and plaque instability were evaluated in LILRB4-/-ApoE-/- and ApoE-/- mice fed a high-fat diet (HFD). We found that LILRB4 was located primarily in macrophages, and its expression was up-regulated in atherosclerotic lesions from human coronary arteries and mouse aortic roots. LILRB4 deficiency significantly accelerated the development of atherosclerotic lesions and increased the instability of plaques, as evident by the increased infiltration of lipids, decreased amount of collagen components and smooth muscle cells. Moreover, LILRB4 deficiency in bone marrow derived cells promoted the development of atherosclerosis. In vivo and in vitro analyses revealed that the proinflammatory effects of LILRB4 deficiency were mediated by the increased activation of NF-κB signaling due to decreased src homolog 2 domain containing phosphatase (Shp) 1 phosphorylation. In conclusion, the present study indicates that LILRB4 deficiency promotes atherogenesis, at least partly, through reduced Shp1 phosphorylation, which subsequently enhances the NF-κB-mediated inflammatory response. Thus, targetting the ‘LILRB4-Shp1’ axis may be a novel therapeutic approach for atherosclerosis.
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A flurogold labeled-retina flatmount (front) representing surviving retinal ganglion cells, and the chemical structure of trimetazidine (background). In Clinical Science volume 131, issue 18, Wan et al. report that trimetazidine protects retinal ganglion cells against acute glaucoma via the Nrf2/Ho-1 pathway and propose it as a novel therapeutic agent; for details, see pages 2363-2375.
Research Article|
August 10 2017
LILRB4 deficiency aggravates the development of atherosclerosis and plaque instability by increasing the macrophage inflammatory response via NF-κB signaling
Zhou Jiang;
Zhou Jiang
1Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan 430060, China
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
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Juan-Juan Qin;
Juan-Juan Qin
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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Yaxing Zhang;
Yaxing Zhang
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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Wen-Lin Cheng;
Wen-Lin Cheng
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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Yan-Xiao Ji;
Yan-Xiao Ji
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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Fu-Han Gong;
Fu-Han Gong
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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Xue-Yong Zhu;
Xue-Yong Zhu
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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Yan Zhang;
Yan Zhang
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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Zhi-Gang She;
Zhi-Gang She
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
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Zan Huang;
1Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan 430060, China
Correspondence: Zan Huang ([email protected]) or Hongliang Li ([email protected])
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Hongliang Li
2Institute of Model Animals of Wuhan University, Wuhan 430060, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
4Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
Correspondence: Zan Huang ([email protected]) or Hongliang Li ([email protected])
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Publisher: Portland Press Ltd
Received:
March 08 2017
Revision Received:
July 05 2017
Accepted:
July 25 2017
Accepted Manuscript online:
July 25 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (17): 2275–2288.
Article history
Received:
March 08 2017
Revision Received:
July 05 2017
Accepted:
July 25 2017
Accepted Manuscript online:
July 25 2017
Citation
Zhou Jiang, Juan-Juan Qin, Yaxing Zhang, Wen-Lin Cheng, Yan-Xiao Ji, Fu-Han Gong, Xue-Yong Zhu, Yan Zhang, Zhi-Gang She, Zan Huang, Hongliang Li; LILRB4 deficiency aggravates the development of atherosclerosis and plaque instability by increasing the macrophage inflammatory response via NF-κB signaling. Clin Sci (Lond) 1 September 2017; 131 (17): 2275–2288. doi: https://doi.org/10.1042/CS20170198
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