Sphingosine signaling and atherogenesis  

作　　者：Cang-baoXU JacobHANSEN-SCHWARTZ LarsEDVINSSON 

机构地区：[1]DivisionofExperimentalVascularResearch,InstituteofMedicine,LundUniversity,Sweden [2]DepartmentofClinicalExperimentalResearch,GlostrupUniversityHospital,Glostrup,Denmark

出　　处：《Acta Pharmacologica Sinica》2004年第7期849-854,共6页中国药理学报（英文版）

基　　金：This work is supported by Swedish Research Council (grandNo5958).

摘　　要：Sphingosine-1-phosphate (S1P) has diverse biological functions acting insidecells as a second messenger to regulate cell proliferation and survival, and extracellularly, as aligand for a group of G protein-coupled receptors (GPCRs) named the endothelial differentiation gene(EDG) family. Five closely related GPCRs of EDG family (EDG1, EDG3, EDG5, EDG6, and EDG8) haverecently been identified as high-affinity S1P receptors. These receptors are coupled via Gi, Gq,G_(12/13), and Rho. The signaling pathways are linked to vascular cell migration, proliferation,apoptosis, intracellular Ca^(2+) mobilization, and expression of adhesion molecules. The formationof an atherosclerotic lesion occurs through activation of cellular events that include monocyteadhesion to the endothelium and vascular smooth muscle cell (VSMC) migration and proliferation.Thus, S1P signaling may play an important role in the pathogenesis of atherosclerotic vasculardisease. This review highlights S1P signalling in vascular cells and its involvement in theformation of atherosclerotic lesions.Sphingosine-1-phosphate (S1P) has diverse biological functions acting insidecells as a second messenger to regulate cell proliferation and survival, and extracellularly, as aligand for a group of G protein-coupled receptors (GPCRs) named the endothelial differentiation gene(EDG) family. Five closely related GPCRs of EDG family (EDG1, EDG3, EDG5, EDG6, and EDG8) haverecently been identified as high-affinity S1P receptors. These receptors are coupled via Gi, Gq,G_(12/13), and Rho. The signaling pathways are linked to vascular cell migration, proliferation,apoptosis, intracellular Ca^(2+) mobilization, and expression of adhesion molecules. The formationof an atherosclerotic lesion occurs through activation of cellular events that include monocyteadhesion to the endothelium and vascular smooth muscle cell (VSMC) migration and proliferation.Thus, S1P signaling may play an important role in the pathogenesis of atherosclerotic vasculardisease. This review highlights S1P signalling in vascular cells and its involvement in theformation of atherosclerotic lesions.

关 键 词：sphingosine 1-phosphate sphingosine kinase sphingosine-1-phosphatereceptors ENDOTHELIUM MYOCARDIUM smooth muscle ARTERIOSCLEROSIS 

分 类 号：R543.5[医药卫生—心血管疾病]