A study on the expression of FGF-21 and NF-κB pathway in the tissues of atherosclerotic mice

Z.-C. Pan, S.-P. Wang, T.-T. Ou, H. Liu, J.-W. Ma, W.-X. Wang, W.-Y. Fang, X.-K. Qu, M. Zhang

Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. zhangminxk@126.com

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• Pharmacology

OBJECTIVE: To study the relationship between the expressions of fibroblast growth factor (FGF)-21 and NF-κB signal transduction pathway in the tissues of atherosclerotic mice.

MATERIALS AND METHODS: A total of 40 apoE-/- male mice at 8 weeks were selected and randomly divided into 4 groups. 10 mice in group A were normally fed with diet. 10 mice in group B were fed with high-fat diet. 10 mice in group C were fed with high-fat diet + pravastatin. 10 mice in group D were fed with high-fat diet + subcutaneous injection of exogenous recombinant FGF-21 protein. Another 10 C57BL/6J mice at 8 weeks were normally fed with diet (group E). They were killed after 12 weeks to collect retinal venous blood. ELISA method was applied to detect the levels of serum FGF-21, NF-κB, monocyte chemo attractant protein (MCP-1), matrix metalloproteinase (MMP)-9 and TNF-α. Immunohistochemical staining and RT-PCR method were applied to detect the expression of FGF-21 in aortic arch and liver tissues. RT-PCR method and Western blot method were applied to detect the expression of NF-κB, MCP-1, MMP-9 and TNF-α in aortic arch and liver tissues.

RESULTS: The levels of serum FGF-21, NF-κB, MCP-1, MMP-9 and TNF-α in group B were higher than those of group A and group E, and those of group C and group D were lower than those of group B (except FGF-21 in group D). The differences had statistical significance (p<0.05). The positive staining rates of FGF-21 in endothelial cells of aortic arch and liver tissues in group B were higher than those group A and group E, and those of group C and group D were lower than those of group B. The differences had statistical significance (p<0.05). The expression levels of FGF-21mRNA, NF-κB, MCP-1, MMP-9, TNF-αmRNA and protein in endothelial cells of aortic arch and liver tissues in group B were higher than those group A and group E, and those of group C and group D were lower than those of group B. The differences had statistical significance (p<0.05).

CONCLUSIONS: FGF-21 may participate in the occurrence of atherosclerosis (AS), which is related to the activation of the NF-κB pathway. Lipid-lowering therapy can inhibit the activation of FGF-21 and NF-κB. Exogenous FGF-21 can also lower the activation of NF-κB and interpose in atherosclerosis process.

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