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Cardiovascular Research Advance Access first published online on March 15, 2009
This version [Corrected Proof] published online on March 31, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp088
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Regulation of vascular physiology and pathology by the S1P2 receptor subtype

Athanasia Skoura and Timothy Hla*

Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030-3501, USA

* Corresponding author. Tel: +1 860 679 4128; fax: +1 860 679 1201. E-mail address: hla{at}nso2.uchc.edu

Sphingosine-1-phosphate (S1P) is now recognized as a lipid mediator that acts via G-protein-coupled receptors. S1P receptors couple to various heterotrimeric G-proteins and regulate downstream targets and ultimately cell behaviour. The prototypical S1P1 receptor is known to couple to Gi and regulates angiogenesis, vascular development, and immune cell trafficking. In this review, we focus our attention on the S1P2 receptor, which has a unique G-protein-coupling property in that it preferentially activates the G12/13 pathway. Recent studies indicate that the S1P2 receptor regulates critical intracellular signalling pathways, such as Rho GTPase, the phosphatase PTEN, and VE-cadherin-based adherens junctions. Analysis of mutant mice has revealed the critical role of this receptor in inner ear physiology, heart and vascular development, vascular remodelling, and vascular tone, permeability, and angiogenesis in vertebrates. These studies suggest that selective modulation of S1P2 receptor function by pharmacological tools may be useful in a variety of pathological conditions.

KEYWORDS Sphingosine-1-phosphate; Angiogenesis; Vascular permeability; Inflammation; Retinopathy

Time for primary review: 34 days


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