title: Targeting sphingosine-1-phosphate signalling for cardioprotection.
abstract: Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid generated by the sphingosine kinase (SK1 or SK2)-catalysed phosphorylation of sphingosine. Plasma S1P is carried in high-density lipoprotein (HDL) or bound to albumin and is reported to arise from activated platelets and erythrocytes. In addition, extracellular SK1 released from vascular endothelial cells may also contribute to plasma S1P levels. S1P exerts its effects through a family of five high affinity S1P-specific G protein-coupled receptors (GPCRs), S1P(1-5). Various S1P receptors are present in the cardiovascular system, including cardiac tissue. Additionally, intracellular S1P may have a second messenger action. Since S1P is recognised as a survival factor in many tissues, there has been much interest in S1P as a cardioprotective agent. Recent evidence indicates that S1P can pre-condition and post-condition the heart and that the cardioprotective effect of HDL may be because of its S1P content. In addition, evidence is emerging that the cardioprotective effects of cannabinoids and S1P may be linked.
authors.affiliation: Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. s.kennedy@bio.gla.ac.uk
authors.forename: Simon
authors.initials: S
authors.lastname: Kennedy
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Kane
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Pyne
authors.forename: Susan
authors.initials: S
authors.lastname: Pyne
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002319:Cardiovascular System / Q000378:metabolism / Q000503:physiopathology; D016503:Drug Delivery Systems; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008246:Lysophospholipids / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine