科学研究
20170725 LILRB4 deficiency aggravates the development of atherosclerosis and plaque instability by increasing the macrophage inflammatory response via NF-κB signaling.
发布时间:2017-07-31  来源:  阅读次数:

Clin Sci (Lond).2017 Jul 25. pii: CS20170198. doi: 10.1042/CS20170198. [Epub ahead of print]

LILRB4 deficiency aggravates the development of atherosclerosis and plaque instability by increasing the macrophage inflammatory response via NF-κB signaling.

Jiang Z1,Qin JJ2,Zhang Y2,Cheng WL2,Ji YX3,Gong FH2,Zhu XY2,Zhang Y2,She ZG2,Huang Z1,Li H4.

 

Abstract

Atherosclerosisis a chronic inflammatory disease. LILRB4 is associated with the pathological processes of various inflammatorydiseases. However, the potential function and underlying mechanisms of LILRB4 in atherogenesis remain to be investigated. In this study, LILRB4 expression was examined in both human and mouse atherosclerotic plaques. The effects and possible mechanisms ofLILRB4 in atherogenesis and plaque instability were evaluated in LILRB4-/-ApoE-/-and ApoE-/-mice fed a high-fat diet. We found thatLILRB4 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 evidenced 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 pro-inflammatory effects of LILRB4 deficiency were mediated by the increased activation of NF-κBsignaling due to decreased Shp1 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-mediatedinflammatory response. Thus, targeting the "LILRB4-Shp1" axis may be a novel therapeutic approach for atherosclerosis.

©2017 The Author(s).

KEYWORDS:

LILRB4; NF-κB; atherosclerosis; inflammation; macrophage

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