Summary
Sphingosine-1-phosphate (S1P) is a bioactive lipid generated in the intracellular
membranes from the metabolism of sphingomyelin. Once secreted/exported by cells of
haematopoietic origin and vascular cells S1P interacts with plasma proteins and accumulates
in high-density lipoprotein (HDL). Growing evidence indicates that HDL-associated
S1P is responsible for the beneficial effects of these lipoproteins on vasorelaxation,
cell survival, cell adhesiveness, angiogenesis and synthesis of two powerful endogenous
anti-atherogenic and anti-thrombotic molecules such as nitric oxide (NO) and prostacyclin
(PGI2). It is likely that vascular effects of HDL-S1P are regulated by the local expression
of S1P receptors. Five G protein-coupled receptors (S1P1 to S1P5), with differential expression patterns and dissimilar coupling mechanism to G protein
subunits, have been identified in the vasculature. This review is focused on the central
role of S1P as a bioactive component that confers vasculoprotective properties to
HDL by eliciting a wide range of biological responses on endothelial and smooth muscle
cells largely dependent on the up-regulation of NO and prostacyclin.
Keywords
High-density lipoproteins - sphingosine-1-phosphate - prostacyclin - nitric oxide
- vascular function