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Sphingosine signaling and atherogenesis
Cang-bao Xu1, Jacob Hansen-Schwartz, Lars Edvinsson
1Division of Experimental Vascular Research, Institute of Medicine, Lund University, Sweden. Cang-Bao.Xu@med.lu.se
Acta Pharmacologica Sinica
|June 24, 2004
Summary
Sphingosine-1-phosphate (S1P) regulates cell functions. S1P signaling in vascular cells is crucial for the development of atherosclerotic vascular disease, highlighting its role in lesion formation.
Area of Science:
- Biochemistry
- Cell Biology
- Vascular Biology
Background:
- Sphingosine-1-phosphate (S1P) acts as an intracellular second messenger and an extracellular ligand.
- S1P binds to G protein-coupled receptors (GPCRs) of the endothelial differentiation gene (EDG) family.
- Five EDG receptors (EDG1, EDG3, EDG5, EDG6, EDG8) are high-affinity S1P receptors.
Purpose of the Study:
- To review the role of S1P signaling in vascular cells.
- To highlight S1P's involvement in the pathogenesis of atherosclerotic vascular disease.
- To examine S1P signaling pathways in the context of atherosclerotic lesion formation.
Main Methods:
- Literature review of S1P signaling pathways.
- Analysis of S1P receptor coupling to G proteins (Gi, Gq, G12/13, Rho).
- Examination of cellular events in atherosclerotic lesion formation, including monocyte adhesion and VSMC migration/proliferation.
Main Results:
- S1P signaling pathways influence vascular cell migration, proliferation, apoptosis, Ca2+ mobilization, and adhesion molecule expression.
- Atherosclerotic lesion formation involves monocyte adhesion and VSMC migration and proliferation.
- S1P signaling pathways are implicated in these cellular events.
Conclusions:
- S1P signaling is integral to vascular cell function.
- S1P plays a significant role in the pathogenesis of atherosclerotic vascular disease.
- Targeting S1P signaling pathways may offer therapeutic strategies for atherosclerosis.