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A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
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Atheroprotective role of high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P)

Francesco Potì1, Manuela Simoni1, Jerzy-Roch Nofer2

  • 1Department of Biomedical, Metabolic and Neural Sciences-Endocrinology Section, University of Modena and Reggio Emilia, Modena, Italy.

Cardiovascular Research
|June 4, 2014
PubMed

Insights

High-density lipoprotein (HDL) cholesterol levels correlate with reduced atherosclerosis, but HDL-targeted therapies lack benefits. Sphingosine-1-phosphate (S1P) within HDL may offer cardiovascular protection.

Area of Science:

  • Cardiovascular Science
  • Lipid Metabolism
  • Molecular Biology

Background:

  • Epidemiological studies show an inverse relationship between high-density lipoprotein (HDL) cholesterol and atherosclerotic disease.
  • Clinical trials targeting HDL cholesterol have not demonstrated significant cardiovascular risk reduction.
  • This suggests HDL components other than cholesterol may mediate its atheroprotective effects.

Purpose of the Study:

  • To review evidence supporting the role of sphingosine-1-phosphate (S1P) as a key atheroprotective component of HDL.
  • To explore the mechanisms by which S1P, a lysosphingolipid, contributes to cardiovascular health.

Main Methods:

  • Review of epidemiological data linking HDL and atherosclerosis.
  • Analysis of in vitro experimental findings on S1P function.
  • Examination of data from animal models of atherosclerosis.

Main Results:

  • Sphingosine-1-phosphate (S1P) is an integral component of HDL particles.
  • S1P exerts biological activity through specific G protein-coupled receptors.
  • Evidence suggests S1P contributes to the anti-atherogenic properties of HDL.

Conclusions:

  • HDL's atheroprotective effects may be significantly mediated by its S1P content, not just cholesterol levels.
  • S1P represents a potential therapeutic target for cardiovascular disease prevention.
  • Further research into S1P's role in HDL function is warranted.

Keywords:
AtherosclerosisHigh-density lipoproteinsInflammationSphingosine-1-phosphate

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