Study on the effects of dysfunctional sphingosine 1-phosphate signal on arteriosclerosis and thrombosis

1-磷酸鞘氨醇信号功能障碍对动脉硬化和血栓形成影响的研究

• 批准号: 21790316
• 负责人: AOKI Shinya
• 金额: $ 2.66万
• 依托单位: Gifu Pharmaceutical University (2010-2011)Mie University (2009)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790316/
• 关键词: スフィンゴシン1-リン酸; 組織因子; 炎症生因子; 動脈硬化; 血栓症; 血栓; 血管内皮細胞; 赤血球; 血小板; LDL; HDL; アルブミン; トロンボキサンA_2; 動脈硬化症; 血液凝固反応; 血栓形成; 炎症; スフィンゴシン1-リン酸; 組織因子; 炎症生因子; 動脈硬化; 血栓症; 血栓; 血管内皮細胞; 赤血球; 血小板; LDL; HDL; アルブミン; トロンボキサンA_2; 動脈硬化症; 血液凝固反応; 血栓形成; 炎症

Sphingosine 1-phosphate(Sph-1-P), abundantly stored in platelets, is released by the platelets' activation. However, the role of released Sph-1-P from activated platelets is remained unclear. In the present study, it was revealed that, in vascular endothelial cells, 1) the supernatant of the activated platelets(Plt-sup) enhanced TNF-a-induced expression of tissue factor(TF), an initiator of coagulation system, that was stimulated by Sph-1-P into the Plt-sup, 2) that Sph-1-P could enhance the expression of TF induced by inflammatory mediators, and 3) that Sph-1-P promoted TF expression by the induction of the transcriptional factors such as Egr-1, NF-kB and AP-1 through MAPK cascade. These results suggest that Sph-1-P would closely be involved in the exacerbation of arteriosclerosis and thrombosis disease.

血小板的激活释放出大量存储在血小板中的1-磷酸盐（SPH-1-P）。但是，活化血小板释放的SPH-1-P的作用尚不清楚。在本研究中，据表明，在血管内皮细胞中，1）活化血小板（PLT-SUP）的上清液增强了TNF-A诱导的组织因子表达（TF）的表达（TF），一种凝结系统的启动，这是由SPH-1-P刺激的SPH-1-P在PLT-SUP中刺激的，可增强TF的表达，2）TF的表达，2） SPH-1-P通过诱导转录因子（例如EGR-1，​​NF-KB和AP-1）通过MAPK Cascade促进TF表达。这些结果表明，SPH-1-P将与动脉硬化和血栓形成疾病的加剧密切相关。