Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/31691
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    標題: Genistein suppresses leptin-induced proliferation and migration of vascular smooth muscle cells and neointima formation
    作者: Tsai, Yung-Chieh
    Leu, Sy-Ying
    Peng, Yi-Jen
    Lee, Yen-Mei
    Hsu, Chih-Hsiung
    Chou, Shen-Chieh
    Yen, Mao-Hsiung
    Cheng, Pao-Yun
    貢獻者: Chi Mei Med Ctr, Dept Obstet & Gynecol
    Taipei Med Univ, Dept Med
    Chia Nan Univ Pharm & Sci, Dept Sport Management
    Natl Def Med Ctr, Grad Inst Life Sci
    Triserv Gen Hosp, Dept Pathol
    Natl Def Med Ctr
    Natl Def Med Ctr, Dept Pharmacol
    Triserv Gen Hosp, Dept Internal Med, Natl Def Med Ctr
    China Med Univ, Dept Biol Sci & Technol, Coll Biopharmaceut & Food Sci
    Natl Def Med Ctr, Grad Inst Physiol, Dept Physiol & Biophys
    關鍵字: genistein
    Leptin
    MMP2
    carotid artery injury
    reactive oxygen species
    日期: 2017-03
    上傳時間: 2018-11-30 15:53:03 (UTC+8)
    出版者: Wiley
    摘要: Obesity is a strong risk factor for the development of cardiovascular diseases and is associated with a marked increase in circulating leptin concentration. Leptin is a peptide hormone mainly produced by adipose tissue and is regulated by energy level, hormones and various inflammatory mediators. Genistein is an isoflavone that exhibits diverse health-promoting effects. Here, we investigated whether genistein suppressed the atherogenic effect induced by leptin. The A10 cells were treated with leptin and/or genistein, and then the cell proliferation and migration were analysed. The reactive oxygen species (ROS) and proteins levels were also measured, such as p44/42MAPK, cell cycle-related protein (cyclin D1 and p21) and matrix metalloproteinase-2 (MMP-2). Immunohistochemistry and morphometric analysis were used for the neointima formation in a rat carotid artery injury model. Genistein (5 mu M) significantly inhibited both the proliferation and migration of leptin (10 ng/ml)stimulated A10 cells. In accordance with these finding, genistein decreased the leptin-stimulated ROS production and phosphorylation of the p44/42MAPK signal transduction pathway. Meanwhile, genistein reversed the leptin-induced expression of cyclin D1, and cyclin-dependent kinase inhibitor, p21. Genistein attenuated leptin-induced A10 cell migration by inhibiting MMP-2 activity. Furthermore, the leptin (0.25 mg/kg)augmented neointima formation in a rat carotid artery injury model was attenuated in the genistein (5 mg/kg body weight)-treated group when compared with the balloon injury plus leptin group. Genistein was capable of suppressing the atherogenic effects of leptin in vitro and in vivo, and may be a promising candidate drug in the clinical setting.
    關聯: Journal of Cellular and Molecular Medicine, v.21, n.3, pp.422-431
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