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首页> 外文期刊>Journal of atherosclerosis and thrombosis. >Vehicle-dependent Effects of Sphingosine 1-phosphate on Plasminogen Activator Inhibitor-1 Expression
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Vehicle-dependent Effects of Sphingosine 1-phosphate on Plasminogen Activator Inhibitor-1 Expression

机译：1-磷酸鞘氨醇对纤溶酶原激活物抑制剂1表达的车辆依赖性影响。

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Aim : Sphingosine 1-phosphate (S1P) has been suggested to be a positive regulator of plasminogen activator inhibitor 1 (PAI-1) in adipocytes, while some studies are not consistent with this prothrombotic property of S1P. Since S1P is bound to apolipoprotein M (apoM) on HDL or to albumin in plasma, we compared the properties of these two forms on the PAI-1 induction. Methods : We investigated the associations of S1P, apoM, and PAI-1 concentrations in the plasma of normal coronary artery (NCA), stable angina pectoris (SAP), and acute coronary syndrome (ACS) subjects ( n =32, 71, and 38, respectively). Then, we compared the effects of S1P with various vehicles on the PAI-1 expression in 3T3L1 adipocytes. We also investigated the modulation of the PAI-1 levels in mice infected with adenovirus coding apoM. Results : Among ACS subjects, the PAI-1 level was positively correlated with the S1P level, but not the apoM level. In adipocytes, S1P bound to an apoM-rich vehicle induced PAI-1 expression to a lesser extent than the control vehicle, while S1P bound to an apoM-depleted vehicle induced PAI-1 expression to a greater extent than the control vehicle in 3T3L1 adipocytes. Additionally, apoM overexpression in mice failed to modulate the plasma PAI-1 level and the adipose PAI-1 expression level. S1P bound to albumin increased PAI-1 expression through the S1P receptor 2-Rho/ROCK-NFκB pathway. Conclusion : S1P bound to albumin, but not to apoM, induces PAI-1 expression in adipocytes, indicating that S1P can exert different properties on the pathogenesis of vascular diseases, depending on its vehicle.
机译：目的：1-磷酸鞘氨醇（S1P）被认为是脂肪细胞中纤溶酶原激活物抑制剂1（PAI-1）的正调节剂，而一些研究与S1P的这种血栓形成特性并不一致。由于S1P与HDL上的载脂蛋白M（apoM）或血浆中的白蛋白结合，因此我们比较了这两种形式在PAI-1诱导上的特性。方法：我们调查了正常冠状动脉（NCA），稳定型心绞痛（SAP）和急性冠状动脉综合征（ACS）受试者（n = 32、71和29）的血浆中S1P，apoM和PAI-1浓度的关联。 38）。然后，我们比较了S1P与各种媒介物对3T3L1脂肪细胞中PAI-1表达的影响。我们还研究了编码apoM的腺病毒感染的小鼠中PAI-1水平的调节。结果：在ACS受试者中，PAI-1水平与S1P水平呈正相关，但与apoM水平无关。在脂肪细胞中，S1P与富含apoM的媒介物结合诱导的PAI-1表达程度低于对照媒介，而S1P与3a3L1脂肪细胞中与apoM减少媒介物结合诱导的PAI-1表达程度高于对照媒介。 。此外，小鼠中的apoM过表达未能调节血浆PAI-1水平和脂肪PAI-1表达水平。与白蛋白结合的S1P通过S1P受体2-Rho /ROCK-NFκB途径增加了PAI-1的表达。结论：S1P结合白蛋白但不结合apoM诱导脂肪细胞中PAI-1表达，这表明S1P可以根据其媒介物在血管疾病的发病机制中发挥不同的作用。

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