The HMG-CoA reductase inhibitor rosuvastatin inhibits plasminogen activator inhibitor-1 expression and secretion in human adipocytes
The HMG-CoA reductase inhibitor rosuvastatin inhibits plasminogen activator inhibitor-1 expression and secretion in human adipocytes
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DOI：
10.1016/j.atherosclerosis.2007.06.005
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发表时间：
2008-02-01
期刊：
影响因子：
5.3
通讯作者：
Hauner, Hans
中科院分区：
文献类型：
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作者：
Laumen, Helmut;Skurk, Thomas;Hauner, Hans
已知人前脂肪细胞和脂肪细胞产生促动脉粥样硬化因子派-1和促炎细胞因子，并且发现肥胖是这些因子的脂肪产生增加的状态。在本研究中，我们研究了瑞舒伐他汀对人脂肪细胞派-1基因表达的调节作用。人前脂肪细胞、原代培养的脂肪细胞和SGBS细胞系被用作细胞模型。使用各种构建体转染细胞，并将启动子活性测量为荧光素酶活性。采用定量RT-PCR和ELISA法检测派-1的表达。瑞舒伐他汀以浓度依赖性方式抑制派-1 mRNA表达和蛋白分泌。这种作用被类异戊二烯逆转。添加MEK抑制剂和NF kappa B抑制剂也降低了派-1表达和派-1启动子荧光素酶活性。进一步的实验显示，瑞舒伐他汀下调了MEKK-1介导的派-1启动子的激活。总之，我们的数据表明，瑞舒伐他汀通过MEKK-1依赖性而非NF κ B依赖性机制抑制派-1表达和人脂肪细胞释放。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Human preadipocytes and adipocytes are known to produce the proatherogenic factor PAI-1 and proinflammatory cytokines, and obesity was found to be state of increased adipose production of these factors. In the present study, we investigated the effect of rosuvastatin on the regulation of PAI-1 gene expression in human adipocytes. Human preadipocytes, adipocytes in primary culture and the SGBS cell line were used as cell models. Cells were transfected using various constructs and promoter activity was measured as luciferase activity. PAI-1 expression was measured by quantitative RT-PCR and ELISA. Rosuvastatin inhibited PAI-1 mRNA expression and secretion of the protein in a concentration-dependent manner. This effect was reversed by isoprenoids. Addition of MEK-inhibitors and NF kappa B inhibitors also reduced PAI-1 expression and PAI-1 promoter luciferase activity. Further experiments revealed that rosuvastatin down-regulated the MEKK-1 mediated activation of the PAI-1 promoter. In conclusion our data suggest that rosuvastatin inhibits PAI-1 expression and release from human adipocytes via a MEKK-1-dependent but not a NF kappa B-dependent mechanism. (c) 2007 Elsevier Ireland Ltd. All rights reserved.