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Sphingosine 1-phosphate signaling in atherosclerosis and vascular biology
Kenichi Tamama1, Fumikazu Okajima
1Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
Purpose Of Review:
Sphingosine 1-phosphate is a novel lipid mediator which exerts various actions on endothelial cells and vascular smooth muscle cells. In this review, we discuss the latest findings about the molecule in vascular biology.
Recent Findings:
It has been demonstrated that most sphingosine 1-phosphate-induced actions are mediated by the Edg-family of its receptors. Sphingosine 1-phosphate stimulates the migration and proliferation of endothelial cells and is cytoprotective towards them. The involvement of phosphoinositide 3-kinase and nitric oxide in sphingosine 1-phosphate downstream signaling in endothelial cells was recently reported, as was the enhancement of endothelial barrier integrity induced by the molecule. Sphingosine 1-phosphate inhibits migration of vascular smooth muscle cells and this inhibition was reported to be mediated by inhibition of Rac. Sphingosine 1-phosphate is concentrated in the lipoprotein fraction in plasma, and high-density lipoprotein exerted endothelial cytoprotection through its component of this molecule.
Summary:
Sphingosine 1-phosphate might play a critical role in the development of atherosclerosis.