Genistein suppresses leptin-induced proliferation and migration of vascular smooth muscle cells and neointima formation.
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 μM) 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.
['Tsai|Yung-Chieh|YC|', 'Leu|Sy-Ying|SY|', 'Peng|Yi-Jen|YJ|', 'Lee|Yen-Mei|YM|', 'Hsu|Chih-Hsiung|CH|', 'Chou|Shen-Chieh|SC|', 'Yen|Mao-Hsiung|MH|', 'Cheng|Pao-Yun|PY|']
D000818:Animals D020212:Carotid Artery Injuries D002465:Cell Movement D049109:Cell Proliferation D019938:Cyclin D1 D050759:Cyclin-Dependent Kinase Inhibitor p21 D019833:Genistein D020738:Leptin D008297:Male D020778:Matrix Metalloproteinase 2 D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D058426:Neointima D010766:Phosphorylation D051381:Rats D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D015398:Signal Transduction
genistein Leptin reactive oxygen species carotid artery injury MMP2