Document Detail


Myeloid-specific IκB kinase β deficiency decreases atherosclerosis in low-density lipoprotein receptor-deficient mice.
MedLine Citation:
PMID:  23023371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Inflammatory responses are the driving force of atherosclerosis development. IκB kinase β (IKKβ), a central coordinator in inflammation through regulation of nuclear factor-κB, has been implicated in the pathogenesis of atherosclerosis. Macrophages play an essential role in the initiation and progression of atherosclerosis, yet the role of macrophage IKKβ in atherosclerosis remains elusive and controversial. This study aims to investigate the impact of IKKβ expression on macrophage functions and to assess the effect of myeloid-specific IKKβ deletion on atherosclerosis development.
METHODS AND RESULTS: To explore the issue of macrophage IKKβ involvement of atherogenesis, we generated myeloid-specific IKKβ-deficient low-density lipoprotein receptor-deficient mice (IKKβ(ΔMye)LDLR(-/-)). Deficiency of IKKβ in myeloid cells did not affect plasma lipid levels but significantly decreased diet-induced atherosclerotic lesion areas in the aortic root, brachiocephalic artery, and aortic arch of low-density lipoprotein receptor-deficient mice. Ablation of myeloid IKKβ attenuated macrophage inflammatory responses and decreased atherosclerotic lesional inflammation. Furthermore, deficiency of IKKβ decreased adhesion, migration, and lipid uptake in macrophages.
CONCLUSIONS: The present study demonstrates a pivotal role for myeloid IKKβ expression in atherosclerosis by modulating macrophage functions involved in atherogenesis. These results suggest that inhibiting nuclear factor-κB activation in macrophages may represent a feasible approach to combat atherosclerosis.
Authors:
Se-Hyung Park; Yipeng Sui; Florence Gizard; Jinxian Xu; Jennifer Rios-Pilier; Robert N Helsley; Seong-Su Han; Changcheng Zhou
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-27
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  32     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-01-29     Revised Date:  2014-04-16    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2869-76     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Atherosclerosis / metabolism,  pathology,  prevention & control*
Cell Adhesion
Cell Movement
Disease Models, Animal
I-kappa B Kinase / deficiency*,  genetics,  metabolism
Lipid Metabolism
Macrophages / metabolism,  pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells / metabolism*
Receptors, LDL / deficiency*,  genetics,  metabolism
Grant Support
ID/Acronym/Agency:
5T32HL072743/HL/NHLBI NIH HHS; P20 RR021954/RR/NCRR NIH HHS; P20GM103527/GM/NIGMS NIH HHS; P20RR021954/RR/NCRR NIH HHS; P30 HL101300/HL/NHLBI NIH HHS; P30HL101300/HL/NHLBI NIH HHS; T32 HL072743/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, LDL; EC 2.7.11.10/I-kappa B Kinase
Comments/Corrections

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