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Cardiovascular Research Advance Access [Accepted Manuscript] published online on February 20, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp070
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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.

Sphingosine-1-phosphate as a mediator of high-density lipoprotein effects in cardiovascular protection

Katherine Sattler and Bodo Levkau

Institute of Pathophysiology, Universitätsklinikum Essen, Germany

Corresponding author: Prof. Dr. Bodo Levkau, Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstr. 55, 45122 Essen, Germany, bodo.levkau{at}uni-due.de, phone: ++49-201-723-4414, fax: ++49-201-723-4413

Sphingosine-1-phosphate (S1P) has gained special attention in the high-density lipoprotein (HDL) field because HDL is the most prominent plasma carrier of S1P and because the S1P content of HDL may be responsible for many of the pleiotropic functions of HDL. This revelation has come from the evidence that HDL employ S1P receptors and signalling pathways to implement several HDL-ascribed biological effects as diverse as endothelial nitric oxide production, vasodilation, survival, and cardioprotection. This review focuses on HDL effects that are completely or partially mediated by the S1P content of the HDL particle and differentiates them from genuine HDL effects that are S1P-independent. Conversely, clear differences exist between the biological functions of S1P and HDL. In addition, the functional properties of "free" S1P appear to be sometimes distinct from those of HDL-associated S1P. The nature of the physical interactions between HDL and local and systemic S1P production will be discussed as well as their consequences for organ function. Finally, we will discuss the potential benefits and limitations of S1P analogues as a new class of functional HDL mimetics for cardiovascular therapy.

KEYWORDS High-density lipoproteins (HDL); sphingosine-1-phosphate (S1P); cardiovascular protection

Time for primary review: 32 Days


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