Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1582, Issue 1-3, Pages 228-239Publisher
ELSEVIER
DOI: 10.1016/S1388-1981(02)00176-2
Keywords
sphingosine 1-phosphate; angiogenesis; vascular development; lipid mediator; endothelial cell; smooth muscle cell
Funding
- NHLBI NIH HHS [R01 HL 61751, HL 69340, P01 HL 58064] Funding Source: Medline
- NIGMS NIH HHS [GM 43880] Funding Source: Medline
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Investigations carried out over the past 3 years have implicated a key role for sphingosine 1-phosphate (SPP) in angiogenesis and blood vessel maturation. SPP is capable of inducing almost every aspect of angiogenesis and vessel maturation in vitro, including endothelial cell chemotaxis, survival, proliferation, capillary morphogenesis and adherence antigen deployment, as well as stabilizing developing endothelial cell monolayers and recruitment of smooth muscle cells to maturing vessels. Acting in conjunction with protein angiogenic factors, SPP induces prolific vascular development in many established models of angiogenesis in vivo. Thus, SPP is a unique, potent and multifaceted angiogenic agent. while SPP induces angiogenic effects by ligating members of the endothelial differentiation gene (EDG) G-protein-coupled family of receptors, recent studies suggest that endogenously produced SPP may also account for the ability of tyrosine kinase receptors to induce cell migration. Thus, SPP provides a clear link between tyrosine kinase and G-protein-coupled receptor agonists involved in the angiogenic response. However, the mechanisms by which SPP exerts its effects on vascular cells remain unclear, conflicting and controversial. Precise definition of the signalling pathways by which SPP induces specific aspects of the angiogenic response promises to lead to new and effective therapeutic approaches to regulate angiogenesis at sites of tissue damage, neoplastic transformation and inflammation. This review will trace the discovery of SPP as a novel angiogenic factor as it outlines present information on the signalling pathways by which SPP induces its effects on cells of the developing vascular bed. (C) 2002 Elsevier Science B.V. All rights reserved.
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