| First Author | Park SH | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 12 | Pages | 2869-76 |
| PubMed ID | 23023371 | Mgi Jnum | J:207877 |
| Mgi Id | MGI:5559841 | Doi | 10.1161/ATVBAHA.112.254573 |
| Citation | Park SH, et al. (2012) Myeloid-specific IkappaB kinase beta deficiency decreases atherosclerosis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol 32(12):2869-76 |
| abstractText | OBJECTIVE: Inflammatory responses are the driving force of atherosclerosis development. IkappaB kinase beta (IKKbeta), a central coordinator in inflammation through regulation of nuclear factor-kappaB, 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 IKKbeta in atherosclerosis remains elusive and controversial. This study aims to investigate the impact of IKKbeta expression on macrophage functions and to assess the effect of myeloid-specific IKKbeta deletion on atherosclerosis development. METHODS AND RESULTS: To explore the issue of macrophage IKKbeta involvement of atherogenesis, we generated myeloid-specific IKKbeta-deficient low-density lipoprotein receptor-deficient mice (IKKbeta(DeltaMye)LDLR(-/-)). Deficiency of IKKbeta 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 IKKbeta attenuated macrophage inflammatory responses and decreased atherosclerotic lesional inflammation. Furthermore, deficiency of IKKbeta decreased adhesion, migration, and lipid uptake in macrophages. CONCLUSIONS: The present study demonstrates a pivotal role for myeloid IKKbeta expression in atherosclerosis by modulating macrophage functions involved in atherogenesis. These results suggest that inhibiting nuclear factor-kappaB activation in macrophages may represent a feasible approach to combat atherosclerosis. |
