Rodríguez Cristina, González-Díez María, Badimon Lina, Martínez-González José
Centro de Investigación Cardiovascular (CSIC-ICCC), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Thromb Haemost. 2009 Apr;101(4):665-73.
Sphingosine-1-phosphate (S1P) is a bioactive lipid generated in the intracellular membranes from the metabolism of sphingomyelin. Once secreted/exported by cells of haematopoietic origin and vascular cells S1P interacts with plasma proteins and accumulates in high-density lipoprotein (HDL). Growing evidence indicates that HDL-associated S1P is responsible for the beneficial effects of these lipoproteins on vasorelaxation, cell survival, cell adhesiveness, angiogenesis and synthesis of two powerful endogenous anti-atherogenic and anti-thrombotic molecules such as nitric oxide (NO) and prostacyclin (PGI(2)). It is likely that vascular effects of HDL-S1P are regulated by the local expression of S1P receptors. Five G protein-coupled receptors (S1P(1) to S1P(5)), with differential expression patterns and dissimilar coupling mechanism to G protein subunits, have been identified in the vasculature. This review is focused on the central role of S1P as a bioactive component that confers vasculoprotective properties to HDL by eliciting a wide range of biological responses on endothelial and smooth muscle cells largely dependent on the up-regulation of NO and prostacyclin.
鞘氨醇-1-磷酸（S1P）是一种由鞘磷脂代谢产生于细胞内膜的生物活性脂质。一旦由造血来源细胞和血管细胞分泌/输出，S1P就会与血浆蛋白相互作用，并在高密度脂蛋白（HDL）中积累。越来越多的证据表明，与HDL相关的S1P是这些脂蛋白对血管舒张、细胞存活、细胞黏附、血管生成以及两种强大的内源性抗动脉粥样硬化和抗血栓形成分子（如一氧化氮（NO）和前列环素（PGI₂））合成产生有益作用的原因。HDL-S1P的血管效应可能受S1P受体的局部表达调控。在脉管系统中已鉴定出五种G蛋白偶联受体（S1P₁至S1P₅），它们具有不同的表达模式以及与G蛋白亚基不同的偶联机制。本综述聚焦于S1P作为一种生物活性成分的核心作用，它通过在内皮细胞和平滑肌细胞上引发广泛的生物学反应，很大程度上依赖于NO和前列环素的上调，赋予HDL血管保护特性。
