First Author | Fang G | Year | 2012 |
Journal | Am J Pathol | Volume | 181 |
Issue | 5 | Pages | 1530-9 |
PubMed ID | 22940439 | Mgi Jnum | J:190021 |
Mgi Id | MGI:5447857 | Doi | 10.1016/j.ajpath.2012.07.024 |
Citation | Fang G, et al. (2012) Chronic intermittent hypoxia exposure induces atherosclerosis in ApoE knockout mice: role of NF-kappaB p50. Am J Pathol 181(5):1530-9 |
abstractText | Current animal models of chronic intermittent hypoxia (CIH)-induced atherosclerosis have limitations. Mechanisms of CIH-induced atherosclerosis are poorly understood. This study tested new mouse models of CIH-induced atherosclerosis and defined the role of NF-kappaB p50 in CIH-induced atherosclerosis. Mice deficient in apolipoprotein E (ApoE-KO) or in both ApoE and p50 genes (ApoE-p50-DKO) were exposed to sham or CIH. Atherosclerotic lesions on aortic preparations were analyzed. CIH exposure caused atherosclerosis in ApoE-KO mice fed a normal chow diet and with no preexisting atherosclerotic condition in an exposure time-dependent manner. CIH caused more pronounced atherosclerotic lesions in ApoE-p50-DKO mice on a normal chow diet without preexisting atherosclerosis. ApoE-KO and ApoE-p50-DKO mice exposed to CIH for 30 and 9 weeks, respectively, displayed similar areas of atherosclerotic lesions on cross sections of aortic root. P50 gene deletion in ApoE-p50-DKO mice significantly augmented CIH-induced serum levels of tumor necrosis factor-alpha and IL-6, aortic tumor necrosis factor-alpha, and inducible nitric oxide synthase expression and aortic infiltration of Mac3-positive macrophages. CIH caused a greater elevation in serum cholesterol level in ApoE-p50-DKO than in ApoE-KO mice. CIH down-regulated hepatic low-density lipoprotein receptor and HMG-CoA reductase expression in ApoE-p50-DKO but not in ApoE-KO mice. We found two new mouse models that are useful for studying mechanisms and pathways of CIH-induced atherosclerosis. We showed that NF-kappaB p50 protects against CIH-induced atherosclerosis by inhibiting vascular inflammation and hypercholesterolemia. |