Inhibitory Effects of Ferulic Acid Ethyl Ester (FAEE) on Leptin–Induced Proliferation and Migration of Rat Aortic Smooth Muscle Cells

• Main Authors: Hsiao-Yen Chiang, 江筱豔
• Other Authors: Pao-Yun Cheng
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/87670204196992637004

碩士 === 中國醫藥大學 === 中國藥學暨中藥資源學系碩士班 === 101 === The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is an important pathogenic factor for vascular disorders such as atherosclerosis and restenosis after angioplasty. Leptin is a peptide hormone which plays a central role in the regulation of body weight. Leptin exerts many potentially atherogenic effects such as induction of endothelial dysfunction, migration, hypertrophy and proliferation of VSMC. Ferulic Acid is widely exist in Angelica sinensis, Ligusticum chuanxiong and so on Chinese medicine, has been approved for anti-inflammatory and antioxidant properties. Ferulic Acid Ethyl Ester (FAEE) is an ester derivative of ferulic acid, the latter known for its anti-thrombus, analgesia, and regulation of immunologic function. The aim of this study was to investigate whether FAEE can inhibit the proliferation and migration of vascular smooth muscle cells induced by leptin and the possible molecular mechanism of its action. Rat aortic smooth muscle cells (A10 cells) were serum-starved and subsequently treated with leptin at increasing concentrations (1, 10, 100 ng/mL) for 72h. Both of cell proliferation and migration were measured when the cell treated with leptin and/or FAEE in A10 cells. Phosphorylated p44/42 MAPK, cyclin D1, p21cip1, β-catenine, p27Kip1, MMP-2, MMP-9 protein level were also measured in A10 cells. Results demonstrated that leptin increased the proliferation of A10 cells as well as the phosphorylation of p44/42 MAPK in a concentration-dependent manner in A10 cells. These effect of leptin were significantly reduced by the pretreatment of U0126, a MAPK inhibitor, in A10 cells. There results suggested that leptin-induced cell proliferation were through the phosphorylation of p44/42 MAPK. Furthermore, leptin also significantly increased the expression of cyclin D1, p21cip1 and β-catenine protein, as well as decreased the expression of p27Kip1, a cyclin-dependent kinase inhibitor, in A10 cells. Above effect of leptin were significantly reduced by the pretreatment of FAEE (1, 10 μM) in A10 cells. In transwell migration assay, the A10 cells were seeded into the insert and move through the pores of the membrane at the bottom of the insert. Leptin (10, 100 ng/mL) significantly increased the migration of A10 cells in a concentration-dependent manner. Meanwhile, the expression of MMP-2 and MMP-9 protein were significantly increased when the cell treated with leptin (10 ng/mL). Pretreatment of FAEE (1, 10 μM) significantly inhibited the migration of cells and the expression of MMP-2 and MMP-9 protein induced by leptin (10 ng/mL) in A10 cells. In conclusion, FAEE significantly attenuated the proliferation and migration of cell induced by leptin through the regulation of p44/42 MAPK, cell cycle protein, and MMPs. Therefore, this study provides a rationale for the therapeutic use of FAEE in atherosclerosis.