Lucke Susann, Levkau Bodo
Institute of Pathophysiology, Universitätsklinikum Essen, Essen, Germany.
Cell Physiol Biochem. 2010;26(1):87-96. doi: 10.1159/000315109. Epub 2010 May 18.
The biologically active sphingolipid sphingosine-1-phosphate (S1P) plays key functions in the immune, inflammatory, and cardiovascular systems. In the vasculature, S1P and its receptors are involved in vessel morphogenesis and angiogenesis during embryonic development and in the adult organism both under normal and pathological conditions. Via its actions on endothelial and smooth muscle cells, S1P regulates arterial tone, vascular permeability, and tissue perfusion. Elevated local S1P levels during inflammation induce endothelial adhesion molecules, recruit inflammatory cells, and activate dendritic cells. At the same time, S1P activates a negative feedback loop that consecutively seals endothelial cell-cell contacts, decreases vascular leakage, and inhibits cytokine-induced leukocyte adhesion. Thus S1P determines not only the build-up, magnitude, and duration of an inflammatory reaction but also the pace of its resolution. This review focuses on the role S1P plays in endothelial function, its receptors and signalling pathways, and the role its major carrier high-density lipoproteins (HDL) play in its bioavailability and transport. We will also discuss the potential of interfering with S1P-S1P receptor interactions for the treatment of endothelial disorders and vascular pathologies.
具有生物活性的鞘脂类物质1-磷酸鞘氨醇（S1P）在免疫、炎症和心血管系统中发挥着关键作用。在脉管系统中，S1P及其受体在胚胎发育期间以及在成年生物体的正常和病理条件下均参与血管形态发生和血管生成。通过作用于内皮细胞和平滑肌细胞，S1P调节动脉张力、血管通透性和组织灌注。炎症期间局部S1P水平升高会诱导内皮黏附分子表达、募集炎症细胞并激活树突状细胞。与此同时，S1P激活一个负反馈回路，该回路会依次封闭内皮细胞间连接、减少血管渗漏并抑制细胞因子诱导的白细胞黏附。因此，S1P不仅决定炎症反应的形成、强度和持续时间，还决定其消退的速度。本综述重点关注S1P在内皮功能中的作用、其受体和信号通路，以及其主要载体高密度脂蛋白（HDL）在其生物利用度和转运中的作用。我们还将讨论干扰S1P-S1P受体相互作用在治疗内皮疾病和血管病变方面的潜力。
