title: Chronic intermittent hypoxia exposure induces atherosclerosis in ApoE knockout mice: role of NF-κB p50.
abstract: 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-κB 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-α and IL-6, aortic tumor necrosis factor-α, 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-κB p50 protects against CIH-induced atherosclerosis by inhibiting vascular inflammation and hypercholesterolemia.
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary and Sleep Medicine, the Feinstein Institute for Medical Research, Manhasset, New York, USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Fang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Song
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Ye
authors.forename: Sun-zhong
authors.initials: SZ
authors.lastname: Mao
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Shu Fang
authors.initials: SF
authors.lastname: Liu
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D002908:Chronic Disease; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen; D011973:Receptors, LDL / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D052002:NF-kappa B p50 Subunit; D011973:Receptors, LDL; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen