High-density lipoprotein stimulates endothelial cell migration and survival through sphingosine 1-phosphate and its receptors
High-density lipoprotein stimulates endothelial cell migration and survival through sphingosine 1-phosphate and its receptors
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DOI：
10.1161/01.atv.0000079011.67194.5a
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发表时间：
2003-07-01
影响因子：
8.7
通讯作者：
Okajima, F
中科院分区：
文献类型：
--
作者：
Kimura, T;Sato, K;Okajima, F
血浆高密度脂蛋白（HDL）水平与动脉粥样硬化的风险呈负相关。然而，HDL发挥抗动脉粥样硬化作用的细胞机制还不清楚。在这项研究中，我们专注于HDL的脂质成分作为介质的脂蛋白诱导的antiatherogenicactions.Methods和Results-HDL和鞘氨醇1-磷酸（S1 P）刺激人脐静脉内皮细胞的迁移和生存。这些对HDL和S1 P的反应几乎完全被百日咳毒素和其他细胞内信号通路的特异性抑制剂抑制，尽管迁移和存活的抑制谱是不同的。S1 P受体EDG-1/S1 P（1）和EDG-3/S1 P（3）的反义寡核苷酸可明显抑制HDL刺激的细胞迁移和存活。细胞迁移对两种受体都敏感，但细胞存活仅对S1 P敏感（1）。富含S1 P的组分和从HDL中层析纯化的S1 P刺激细胞迁移，但其余组分不刺激细胞迁移，细胞存活也是如此。结论HDL诱导的内皮细胞迁移和存活可能是由脂蛋白组分S1 P和脂质受体S1 P（1）和S1 P（3）介导的。
Objective-Plasma high-density lipoprotein (HDL) level is inversely correlated with the risk of atherosclerosis. However, the cellular mechanism by which HDL exerts antiatherogenic actions is not well understood. In this study, we focus on the lipid components of HDL as mediators of the lipoprotein-induced antiatherogenic actions.Methods and Results-HDL and sphingosine 1-phosphate (S1P) stimulated the migration and survival of human umbilical vein endothelial cells. These responses to HDL and S1P were almost completely inhibited by pertussis toxin and other specific inhibitors for intracellular signaling pathways, although the inhibition profiles of migration and survival were different. The HDL-stimulated migration and survival of the cells were markedly inhibited by antisense oligonucleotides against the S1P receptors EDG-1/S1P(1) and EDG-3/S1P(3). Cell migration was sensitive to both receptors, but cell survival was exclusively sensitive to S1P(1). The S1P-rich fraction and chromatographically purified S1P from HDL stimulated cell migration, but the rest of the fraction did not, as was the case of the cell survival.Conclusions-HDL-induced endothelial cell migration and survival may be mediated by the lipoprotein component S1P and the lipid receptors S1P(1) and S1P(3).