title: Myeloid-specific IκB kinase β deficiency decreases atherosclerosis in low-density lipoprotein receptor-deficient mice.
abstract: 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.
  
  
  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.affiliation: Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Se-Hyung
authors.initials: SH
authors.lastname: Park
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Sui
authors.forename: Florence
authors.initials: F
authors.lastname: Gizard
authors.forename: Jinxian
authors.initials: J
authors.lastname: Xu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rios-Pilier
authors.forename: Robert N
authors.initials: RN
authors.lastname: Helsley
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Han
authors.forename: Changcheng
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D002465:Cell Movement; D004195:Disease Models, Animal; D051550:I-kappa B Kinase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D011973:Receptors, LDL; D051550:I-kappa B Kinase