title: IKKε knockout prevents high fat diet induced arterial atherosclerosis and NF-κB signaling in mice.
abstract: OBJECTIVE
  Atherosclerosis is a public health concern affecting many worldwide, but its pathogenesis remains unclear. In this study we investigated the role of IKKε during the formation of atherosclerosis and its molecular mechanism in the mouse aortic vessel wall.
  
  
  RESULTS
  C57BL/6 wild-type or IKKε knockout mice bred into the ApoE knockout genetic background were divided into 4 groups: (1) wild-type (WT), (2) ApoE knockout (AK), (3) IKKε knockout (IK), (4) or both ApoE and IKKε knockout (DK). Each group of mice were fed with a high fat diet (HFD) for 12 weeks from 8 weeks of age. Immunohistochemistry and Western blotting analysis demonstrated obvious increases in the expression of IKKε in the AK group compared with the WT group, especially in the intima. Serum lipid levels were significantly higher in the AK and DK groups than in the other two groups. Staining with hematoxylin-eosin and Oil Red, as well as scanning electron microscopy revealed less severe atherosclerotic lesions in the DK group than in the AK group. Immunofluorescence and Western blot analysis demonstrated obvious increases in the expression of NF-κB pathway components and downstream factors in the AK group, especially in the intima, while these increases were blocked in the DK group.
  
  
  CONCLUSIONS
  The knockout of IKKε prevented significant atherosclerosis lesions in the mouse aorta from in both wild-type and ApoE knockout mice fed a HFD, suggesting that IKKε may play a vital role in HFD-induced atherosclerosis and would be an important target for the treatment of atherosclerosis.
authors.affiliation: Division of Nephrology, Department of medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Cao
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Liangpeng
authors.initials: L
authors.lastname: Li
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Qi
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Wan
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D001835:Body Weight; D002467:Cell Nucleus / Q000378:metabolism; D059305:Diet, High-Fat; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004789:Enzyme Activation; D051550:I-kappa B Kinase / Q000235:genetics* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D008055:Lipids; D016328:NF-kappa B; D051550:I-kappa B Kinase