Sphingosine-1-phosphate signaling in the cardiovascular system.

Increasing evidence suggests a key role for the bioactive lipid sphingosine-1-phosphate (S1P) and its G-protein-coupled receptors (S1P(1-5)) in the cardiovascular system. Recent advances in sphingolipid research indicates that cardiomyocyte, vascular smooth muscle and endothelial cell function is greatly influenced by the relative expression and activity both of S1P receptors and of the enzymes involved in sphingolipid metabolism. For instance, the discovery and development of S1P receptor agonists such as FTY720 has clearly indicated the involvement of S1P receptors in the regulation of heart rate. In addition, sphingolipid metabolism induced, for example, by tumour necrosis factor-alpha or angiotensin II plays an important role in vessel structure, function and tone.