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Review
. 2016 Jun 1;21(7):1296-313.
doi: 10.2741/4458.

Implication of sphingosin-1-phosphate in cardiovascular regulation

Ningjun Li  1 , Fan Zhang  2
Affiliations
Review

Implication of sphingosin-1-phosphate in cardiovascular regulation

Ningjun Li et al. Front Biosci (Landmark Ed). .

Abstract

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite generated by phosphorylation of sphingosine catalyzed by sphingosine kinase. S1P acts mainly through its high affinity G-protein-coupled receptors and participates in the regulation of multiple systems, including cardiovascular system. It has been shown that S1P signaling is involved in the regulation of cardiac chronotropy and inotropy and contributes to cardioprotection as well as cardiac remodeling; S1P signaling regulates vascular function, such as vascular tone and endothelial barrier, and possesses an anti-atherosclerotic effect; S1P signaling is also implicated in the regulation of blood pressure. Therefore, manipulation of S1P signaling may offer novel therapeutic approaches to cardiovascular diseases. As several S1P receptor modulators and sphingosine kinase inhibitors have been approved or under clinical trials for the treatment of other diseases, it may expedite the test and implementation of these S1P-based drugs in cardiovascular diseases.

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Figures

Figure 1
Figure 1
Pathway for the biosynthesis of S1P.
Figure 2
Figure 2
Role of S1P signaling in vascular tone. S1P1 & 3 receptors on endothelial cells mediate a vasodilator effect, whereas S1P2 & 3 on vascular smooth muscle cells (VSMCs) mediate a vasoconstrictor effect.
Figure 3
Figure 3
Role of S1P signaling in endothelial barrier. A low level of S1P produces a tight endothelial barrier via S1P1 receptor on endothelial cells (EC), but a high level of S1P induces a loose barrier via S1P3 receptor on ECs.
Figure 4
Figure 4
Role of S1P signaling in atherosclerosis. S1P mainly induces an atheroprotective effect via S1P1 receptor on endothelial and hematopoietic cells and S1P2 & 3 on VSMCs, although S1P2&3 receptors on macrophages have been shown to mediate a pro-atherosclerotic effect.
Figure 5
Figure 5
Role of S1P signaling in blood pressure. S1P1&3-mediated vasodilation reduces blood pressure (BP), whereas S1P2&3-mediated vasoconstriction increases BP. Strong natriuretic effect of S1P via S1P1 on renal tubules may contribute to the long-term control of blood pressure.
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References

    1. Ghosh TK, Bian J, Gill DL. Intracellular calcium release mediated by sphingosine derivatives generated in cells. Science. 1990;248(4963):1653–6. DOI: 10.1126/science.2163543. - PubMed
    1. Zhang H, Desai NN, Olivera A, Seki T, Brooker G, Spiegel S. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J Cell Biol. 1991;114(1):155–67. DOI: 10.1083/jcb.114.1.155. - PMC - PubMed
    1. Sadahira Y, Ruan F, Hakomori S, Igarashi Y. Sphingosine 1-phosphate, a specific endogenous signaling molecule controlling cell motility and tumor cell invasiveness. Proc Natl Acad Sci U S A. 1992;89(20):9686–90. DOI: 10.1073/pnas.89.20.9686. - PMC - PubMed
    1. Kunkel GT, Maceyka M, Milstien S, Spiegel S. Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013;12(9):688–702. DOI: 10.1038/nrd4099. - PMC - PubMed
    1. Liu X, Zhang QH, Yi GH. Regulation of metabolism and transport of sphingosine-1-phosphate in mammalian cells. Mol Cell Biochem. 2012;363(1-2):21–33. DOI: 10.1007/s11010-011-1154-1. - PubMed

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