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LILRB4 deficiency aggravates the development of atherosclerosis and plaque instability by increasing the macrophage inflammatory response via NF-κB signaling
- Source :
- Clinical Science. 131:2275-2288
- Publication Year :
- 2017
- Publisher :
- Portland Press Ltd., 2017.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Inflammation
NF-κB
General Medicine
Biology
medicine.disease
In vitro
Coronary arteries
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
medicine.anatomical_structure
chemistry
In vivo
Immunology
Cancer research
medicine
Phosphorylation
medicine.symptom
Infiltration (medical)
LILRB4
Subjects
Details
- ISSN :
- 14708736 and 01435221
- Volume :
- 131
- Database :
- OpenAIRE
- Journal :
- Clinical Science
- Accession number :
- edsair.doi.dedup.....7e8aa857d53031431add0dd9b7b98c8c