IKK? knockout prevents high fat diet induced arterial atherosclerosis and NF-?B signaling in mice.

ABSTRACT:

Aims

Atherosclerosis is a public health concern affecting many worldwide, but its pathogenesis remains unclear. In this study we investigated the role of IKK? during the formation of atherosclerosis and its molecular mechanism in the mouse aortic vessel wall.

Methods and results

C57BL/6 wild-type or IKK? knockout mice bred into the ApoE knockout genetic background were divided into 4 groups: (1) wild-type (WT), (2) ApoE knockout (AK), (3) IKK? knockout (IK), (4) or both ApoE and IKK? 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 IKK? 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-?B pathway components and downstream factors in the AK group, especially in the intima, while these increases were blocked in the DK group.

Conclusion

The knockout of IKK? prevented significant atherosclerosis lesions in the mouse aorta from in both wild-type and ApoE knockout mice fed a HFD, suggesting that IKK? may play a vital role in HFD-induced atherosclerosis and would be an important target for the treatment of atherosclerosis.

SUBMITTER: Cao C 

PROVIDER: S-EPMC3669140 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature