Myeloid-specific I?B kinase ? deficiency decreases atherosclerosis in low-density lipoprotein receptor-deficient mice.

ABSTRACT: Inflammatory responses are the driving force of atherosclerosis development. I?B kinase ? (IKK?), a central coordinator in inflammation through regulation of nuclear factor-?B, 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 IKK? in atherosclerosis remains elusive and controversial. This study aims to investigate the impact of IKK? expression on macrophage functions and to assess the effect of myeloid-specific IKK? deletion on atherosclerosis development.To explore the issue of macrophage IKK? involvement of atherogenesis, we generated myeloid-specific IKK?-deficient low-density lipoprotein receptor-deficient mice (IKK?(?Mye)LDLR(-/-)). Deficiency of IKK? 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 IKK? attenuated macrophage inflammatory responses and decreased atherosclerotic lesional inflammation. Furthermore, deficiency of IKK? decreased adhesion, migration, and lipid uptake in macrophages.The present study demonstrates a pivotal role for myeloid IKK? expression in atherosclerosis by modulating macrophage functions involved in atherogenesis. These results suggest that inhibiting nuclear factor-?B activation in macrophages may represent a feasible approach to combat atherosclerosis.

SUBMITTER: Park SH 

PROVIDER: S-EPMC3979309 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature