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Metformin inhibits nuclear factor κB activation and decreases serum high-sensitivity C-reactive protein level in experimental atherogenesis of rabbits

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Abstract

Previous studies demonstrated that metformin has obvious antiatherogenic properties, but the exact mechanism remains unclear. Therefore, we established an atherosclerotic rabbit model in order to investigate the potential effects of metformin on transcription factor nuclear factor κB (NF-κB) and serum high-sensitivity C-reactive protein (hs-CRP) level, which had been regarded as proatherogenic factors. New Zealand rabbits were randomly divided into three groups: a control group (n = 8), an atherosclerotic group (AS group, n = 8), and a metformin treatment group (Met group, n = 8). The experimental atherosclerotic rabbit model was successfully established at the end of the 8th week. From the 9th week, rabbits in the Met group were administered with 150 mg/kg metformin daily by gavage. Blood samples were collected at days 0 and 8, and at 16 weeks to detect the level of blood lipid and serum glucose. At the end of the experiment, blood samples were withdrawn for determining serum hs-CRP. Aortic samples were harvested for histomorphometric analysis. Immunohistochemistry and Western blotting were used to detect the expression of NF-κB subunit p65 in nuclear extracts and phosphorylation of inhibitor of nuclear factor κB (IκB) in cytoplasmic extracts. An experimental atherosclerotic rabbit model was successfully established. The expression of nuclear NF-κB subunit p65 and cytoplasmic phosphorylation of IκB protein in the vessel wall was enhanced (P < 0.01, respectively) in the AS group, and serum hs-CRP level was significantly increased in the AS group compared with the control group (3.90 ± 0.25 mg/l versus 1.36 ± 0.14 mg/l, P < 0.01). Treatment with metformin significantly attenuated the progression of aortic atherosclerosis. In the Met group, there was a marked reduction in nuclear NF-κB subunit p65 and cytoplasmic phosphorylation of IκB protein expression (P < 0.01). Serum hs-CRP concentration was also significantly decreased (3.20 ± 0.20 mg/l versus 3.90 ± 0.25 mg/l, P < 0.05). Metformin inhibits the phosphorylation of IκB and the activation of NF-κB in the vessel wall of experimental atherogenesis of rabbits, as well as decreasing the serum level of hs-CRP, thus suggesting that metformin has vascular anti-inflammatory properties, which may be one of its antiatherogenic mechanisms.

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Authors and Affiliations

  1. Department of Cardiology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, P. R. China

    Song-Nan Li, Xiang Wang, Qiu-Tang Zeng, Yi-Bai Feng, Xiang Cheng, Xiao-Bo Mao & Tian-Hong Wang

  2. Department of Echocardiography, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P.R. China

    He-Ping Deng

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  1. Song-Nan Li
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  2. Xiang Wang
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Correspondence to Xiang Wang.

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Li, SN., Wang, X., Zeng, QT. et al. Metformin inhibits nuclear factor κB activation and decreases serum high-sensitivity C-reactive protein level in experimental atherogenesis of rabbits. Heart Vessels 24, 446–453 (2009). https://doi.org/10.1007/s00380-008-1137-7

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  • DOI: https://doi.org/10.1007/s00380-008-1137-7

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