Myeloid-specific IκB kinase β deficiency decreases atherosclerosis in low-density lipoprotein receptor-deficient mice

Se Hyung Park, Yipeng Sui, Florence Gizard, Jinxian Xu, Jennifer Rios-Pilier, Robert N. Helsley, Seong Su Han, Changcheng Zhou

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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. 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 (IKKβLDLR). 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. CONCLUSION-: 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.

Original languageEnglish (US)
Pages (from-to)2869-2876
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number12
DOIs
StatePublished - Dec 2012

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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