Targeting sphingosine-1-phosphate signalling for cardioprotection

S. Kennedy, K.A. Kane, N.J. Pyne, S. Pyne

Research output: Contribution to journalLiterature review

27 Citations (Scopus)

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), S1P1-5. 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.
Original languageEnglish
Pages (from-to)194-201
Number of pages7
JournalCurrent Opinion in Pharmacology
Volume9
Issue number2
DOIs
Publication statusPublished - Apr 2009

Keywords

  • sphingosine-1-phosphate
  • S1P
  • high-density lipoprotein
  • cardioprotection
  • cardiac tissue
  • HDL

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