van der Giet Markus, Tölle Markus, Kleuser Burkhard
Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik mit Schwerpunkt Nephrologie, Hindenburgdamm 30, D-12203 Berlin, Germany.
Biol Chem. 2008 Nov;389(11):1381-90. doi: 10.1515/BC.2008.165.
The typical pathological feature of atherosclerosis is inflammation. In the last years, it has become evident that inhibition of inflammation is one important therapeutic option in atherosclerosis. Recently, sphingolipid sphingosine-1-phosphate (S1P) was identified as a crucial molecule with potent anti-inflammatory properties. Indeed, S1P activates various G protein-coupled receptors, namely S1P1-S1P5. In the vasculature, mainly S1P1-3 receptors are present. FTY720, after phosphorylation to FTY720-P, is an orally active S1P mimetic. FTY720 has been developed for therapy in the field of autoimmune diseases and organ transplantation. In analogy to S1P, FTY720 shows potent anti-inflammatory effects and several groups have tested the in vivo effects of FTY720 on the progression of inflammatory vascular diseases. They could show that S1P receptor activation might lead to a partial inhibition of the progression of atherosclerotic lesions. S1P receptor activation therefore might be a concept for anti-inflammatory drug treatment. However, it is not clear how S1P and FTY720 exactly act on vascular inflammation. This review article gives a brief overview over the known actions of S1P in vascular inflammatory disease.
动脉粥样硬化的典型病理特征是炎症。近年来，抑制炎症已成为动脉粥样硬化的一种重要治疗选择这一点变得很明显。最近，鞘脂类的1-磷酸鞘氨醇（S1P）被确定为一种具有强大抗炎特性的关键分子。实际上，S1P可激活多种G蛋白偶联受体，即S1P1 - S1P5。在脉管系统中，主要存在S1P1 - 3受体。FTY720磷酸化后成为FTY720 - P，是一种口服活性S1P模拟物。FTY720已被开发用于自身免疫性疾病和器官移植领域的治疗。与S1P类似，FTY720显示出强大的抗炎作用，并且有几个研究小组测试了FTY720对炎症性血管疾病进展的体内作用。他们发现S1P受体激活可能会部分抑制动脉粥样硬化病变的进展。因此，S1P受体激活可能是一种抗炎药物治疗的理念。然而，尚不清楚S1P和FTY720究竟如何作用于血管炎症。这篇综述文章简要概述了S1P在血管炎性疾病中的已知作用。
