Sphingosine-1-phosphate and modulation of vascular tone

^{Department of Cardiovascular Physiology, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan}

^{Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Thorn Building, Room 1210A, 75 Francis Street, Boston, MA 02115, USA}

^{Corresponding authors. Tel: +81 87 891 2099 (J.I.)/+1 617 732 7376 (T.M.); fax: +81 87 891 2101 (J.I.)/Fax: +1 617 732 5132 (T.M.).}E-mail addresses: pj.ca.u-awagak.dem@ihsaragi (J.I.)/ude.dravrah@lehcim_samoht (T.M.)

Received 2008 Aug 26; Revised 2009 Jan 30; Accepted 2009 Feb 3.

Abstract

Sphingosine-1-phosphate (S1P) is a phosphorylated product of sphingosine, the core structure of the class of lipids termed sphingolipids. S1P is a naturally occurring lipid metabolite, and usually is present at a concentration of a few 100 nanomolar in human sera. S1P has been found to exert a diverse set of physiological and pathophysiological responses in mammalian tissues through the activation of heterotrimeric G-proteins that in turn modulate the activity of various downstream effecter molecules. In blood vessels, vascular endothelial cells and smooth muscle cells express specific receptors for S1P that modulate vascular tone. This article will provide a brief overview of S1P metabolism in the vasculature and will discuss some of the pathways whereby S1P regulates intracellular signal transduction pathways in endothelial and smooth muscle cells, leading to the activation of both vasorelaxation and vasoconstriction responses.

Keywords: Vasoactive agents, Lipid signalling, Receptors, G-proteins, eNOS

Abstract

References

1. Hla TPhysiological and pathological actions of sphingosine 1-phosphate. Semin Cell Dev Biol. 2004;15:513–520.[PubMed][Google Scholar]
2. Hla T, Lee MJ, Ancellin N, Paik JH, Kluk MJLysophospholipids–receptor revelations. Science. 2001;294:1875–1878.[PubMed][Google Scholar]
3. Liu Y, Wada R, Yamashita T, Mi Y, Deng CX, Hobson JP, et al Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J Clin Invest. 2000;106:951–961.[Google Scholar]
4. Kupperman E, An S, Osborne N, Waldron S, Stainier DYA sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development. Nature. 2000;406:192–195.[PubMed][Google Scholar]
5. Payne SG, Milstien S, Spiegel SSphingosine-1-phosphate: dual messenger functions. FEBS Lett. 2002;531:54–57.[PubMed][Google Scholar]
6. Cavalli AL, O’Brien NW, Barlow SB, Betto R, Glembotski CC, Palade PT, et al Expression and functional characterization of SCaMPER: a sphingolipid-modulated calcium channel of cardiomyocytes. Am J Physiol Cell Physiol. 2003;284:C780–C790.[PubMed][Google Scholar]
7. Futerman AH, Hannun YAThe complex life of simple sphingolipids. EMBO Rep. 2004;5:777–782.[Google Scholar]
8. Spiegel S, Milstien SFunctions of the multifaceted family of sphingosine kinases and some close relatives. J Biol Chem. 2007;282:2125–2129.[PubMed][Google Scholar]
9. Yatomi YPlasma sphingosine 1-phosphate metabolism and analysis. Biochim Biophys Acta. 2008;1780:606–611.[PubMed][Google Scholar]
10. Okajima FPlasma lipoproteins behave as carriers of extracellular sphingosine 1-phosphate: is this an atherogenic mediator or an anti-atherogenic mediator? Biochim Biophys Acta. 2002;1582:132–137.[PubMed][Google Scholar]
11. Yatomi Y, Yamamura S, Ruan F, Igarashi YSphingosine 1-phosphate induces platelet activation through an extracellular action and shares a platelet surface receptor with lysophosphatidic acid. J Biol Chem. 1997;272:5291–5297.[PubMed][Google Scholar]
12. Tani M, Sano T, Ito M, Igarashi YMechanisms of sphingosine and sphingosine 1-phosphate generation in human platelets. J Lipid Res. 2005;46:2458–2467.[PubMed][Google Scholar]
13. Kobayashi N, Nishi T, Hirata T, Kihara A, Sano T, Igarashi Y, et al Sphingosine 1-phosphate is released from the cytosol of rat platelets in a carrier-mediated manner. J Lipid Res. 2006;47:614–621.[PubMed][Google Scholar]
14. Mizugishi K, Yamashita T, Olivera A, Miller GF, Spiegel S, Proia RLEssential role for sphingosine kinases in neural and vascular development. Mol Cell Biol. 2005;25:11113–11121.[Google Scholar]
15. Pappu R, Schwab SR, Cornelissen I, Pereira JP, Regard JB, Xu Y, et al Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science. 2007;316:295–298.[PubMed][Google Scholar]
16. Xia P, Gamble JR, Rye KA, Wang L, Hii CS, Cockerill P, et al Tumor necrosis factor-alpha induces adhesion molecule expression through the sphingosine kinase pathway. Proc Natl Acad Sci USA. 1998;95:14196–14201.[Google Scholar]
17. Ancellin N, Colmont C, Su J, Li Q, Mittereder N, Chae SS, et al. Extracellular export of sphingosine kinase-1 enzyme. Sphingosine 1-phosphate generation and the induction of angiogenic vascular maturation. J Biol Chem. 2002;277:6667–6675.[PubMed]
18. Venkataraman K, Lee YM, Michaud J, Thangada S, Ai Y, Bonkovsky HL, et al Vascular endothelium as a contributor of plasma sphingosine 1-phosphate. Circ Res. 2008;102:669–676.[Google Scholar]
19. Peter BF, Lidington D, Harada A, Bolz HJ, Vogel L, Heximer S, et al Role of sphingosine-1-phosphate phosphohydrolase 1 in the regulation of resistance artery tone. Circ Res. 2008;103:315–324.[Google Scholar]
20. Loscalzo J, Welch GNitric oxide and its role in the cardiovascular system. Prog Cardiovasc Dis. 1995;38:87–104.[PubMed][Google Scholar]
21. Dudzinski DM, Igarashi J, Greif D, Michel TThe regulation and pharmacology of endothelial nitric oxide synthase. Annu Rev Pharmacol Toxicol. 2006;46:235–276.[PubMed][Google Scholar]
22. Igarashi J, Michel TAgonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae: eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction. J Biol Chem. 2000;275:32363–32370.[PubMed][Google Scholar]
23. Igarashi J, Bernier SG, Michel TSphingosine 1-phosphate and activation of endothelial nitric oxide synthase: differential regulation of Akt and MAP kinase pathways by EDG and bradykinin receptors in vascular endothelial cells. J Biol Chem. 2001;276:12420–12426.[PubMed][Google Scholar]
24. Lee MJ, Thangada S, Claffey KP, Ancellin N, Liu CH, Kluk M, et al Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell. 1999;99:301–312.[PubMed][Google Scholar]
25. Morales-Ruiz M, Lee MJ, Zoellner S, Gratton JP, Scotland R, Shiojima I, et al Sphingosine-1-phosphate activates Akt, nitric oxide production and chemotaxis through a Gi-protein/ phosphoinositide 3-kinase pathway in endothelial cells. J Biol Chem. 2001;276:19672–19677.[PubMed][Google Scholar]
26. Igarashi J, Miyoshi M, Hashimoto T, Kubota Y, Kosaka HStatins induce S1P(1) receptors and enhance endothelial nitric oxide production in response to high-density lipoproteins. Br J Pharmacol. 2007;150:470–479.[Google Scholar]
27. Igarashi J, Michel T. Sphingosine 1-phosphate and isoform-specific activation of phosphoinositide 3-kinase beta. Evidence for divergence and convergence of receptor-regulated endothelial nitric-oxide synthase signaling pathways. J Biol Chem. 2001;276:36281–36288.[PubMed]
28. Kimura T, Sato K, Kuwabara A, Tomura H, Ishiwara M, Kobayashi I, et al Sphingosine 1-phosphate may be a major component of plasma lipoproteins responsible for the cytoprotective actions in human umbilical vein endothelial cells. J Biol Chem. 2001;276:31780–31785.[PubMed][Google Scholar]
29. Dantas AP, Igarashi J, Michel TSphingosine 1-phosphate and control of vascular tone. Am J Physiol Heart Circ Physiol. 2003;284:H2045–H2052.[PubMed][Google Scholar]
30. Nofer JR, Van Der Giet M, Tolle M, Wolinska I, Von Wnuck Lipinski K, Baba HA, et al HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P(3) J Clin Invest. 2004;113:569–581.[Google Scholar]
31. Theilmeier G, Schmidt C, Herrmann J, Keul P, Schafers M, Herrgott I, et al High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P₃ lysophospholipid receptor. Circulation. 2006;114:1403–1409.[PubMed][Google Scholar]
32. Igarashi J, Erwin PA, Dantas AP, Chen H, Michel TVEGF induces S1P₁ receptors in endothelial cells: implications for cross-talk between sphingolipid and growth factor receptors. Proc Natl Acad Sci USA. 2003;100:10664–10669.[Google Scholar]
33. Hla T, Maciag TAn abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors. J Biol Chem. 1990;265:9308–9313.[PubMed][Google Scholar]
34. Shu X, Wu W, Mosteller RD, Broek DSphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases. Mol Cell Biol. 2002;22:7758–7768.[Google Scholar]
35. Endo A, Nagashima KI, Kurose H, Mochizuki S, Matsuda M, Mochizuki NSphingosine 1-phosphate induces membrane ruffling and increases motility of human umbilical vein endothelial cells via vascular endothelial growth factor receptor and CrkII. J Biol Chem. 2002;277:23747–23754.[PubMed][Google Scholar]
36. Tanimoto T, Jin ZG, Berk BCTransactivation of vascular endothelial growth factor (VEGF) receptor Flk-1/KDR is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS) J Biol Chem. 2002;277:42997–43001.[PubMed][Google Scholar]
37. Levine YC, Li GK, Michel TAgonist-modulated regulation of AMP-activated protein kinase (AMPK) in endothelial cells: evidence for an AMPK → Rac1 → Akt → endothelial nitric-oxide synthase pathway. J Biol Chem. 2007;282:20351–20364.[PubMed][Google Scholar]
38. Cai HHydrogen peroxide regulation of endothelial function: origins, mechanisms, and consequences. Cardiovasc Res. 2005;68:26–36.[PubMed][Google Scholar]
39. Igarashi J, Miyoshi M, Hashimoto T, Kubota Y, Kosaka HHydrogen peroxide induces S1P₁ receptors and sensitizes vascular endothelial cells to sphingosine 1-phosphate, a platelet-derived lipid mediator. Am J Physiol Cell Physiol. 2007;292:C740–C748.[PubMed][Google Scholar]
40. Mason RP, Walter MF, Jacob RFEffects of HMG-CoA reductase inhibitors on endothelial function: role of microdomains and oxidative stress. Circulation. 2004;109:II34–II41.[PubMed][Google Scholar]
41. Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, et al Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004;427:355–360.[PubMed][Google Scholar]
42. Kabashima K, Haynes NM, Xu Y, Nutt SL, Allende ML, Proia RL, et al Plasma cell S1P₁ expression determines secondary lymphoid organ retention versus bone marrow tropism. J Exp Med. 2006;203:2683–2690.[Google Scholar]
43. Shaul PW, Anderson RGWRole of plasmalemmal caveolae in signal transduction. Am J Physiol. 1998;275:L843–L851.[PubMed][Google Scholar]
44. Sase K, Michel TExpression and regulation of endothelial nitric oxide synthase. Trends Cardiovasc Med. 1997;7:28–37.[PubMed][Google Scholar]
45. Busconi L, Michel T. Endothelial nitric oxide synthase. N-terminal myristoylation determines subcellular localization. J Biol Chem. 1993;268:8410–8413.[PubMed]
46. Yeh CD, Duncan JA, Yamashita S, Michel TDepalmitoylation of endothelial nitric-oxide synthase by acyl-protein thioesterase 1 is potentiated by Ca^-calmodulin.J Biol Chem. 1999;274:33148–33154.[PubMed][Google Scholar]
47. Shaul PWRegulation of endothelial nitric oxide synthase: location, location, location. Annu Rev Physiol. 2002;64:749–774.[PubMed][Google Scholar]
48. Feron O, Belhassen L, Kobzik L, Smith TW, Kelly RA, Michel T. Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem. 1996;271:22810–22814.[PubMed]
49. Michel JB, Feron O, Sase K, Prabhakar P, Michel T. Caveolin versus calmodulin. Counterbalancing allosteric modulators of endothelial nitric oxide synthase. J Biol Chem. 1997;272:25907–25912.[PubMed]
50. Robinson LJ, Busconi L, Michel TAgonist-modulated palmitoylation of endothelial nitric oxide synthase. J Biol Chem. 1995;270:995–998.[PubMed][Google Scholar]
51. Gonzalez E, Kou R, Lin AJ, Golan DE, Michel TSubcellular targeting and agonist-induced site-specific phosphorylation of endothelial nitric-oxide synthase. J Biol Chem. 2002;277:39554–39560.[PubMed][Google Scholar]
52. Michel T, Feron ONitric oxide synthases: which, where, how, and why? J Clin Invest. 1997;100:2146–2152.[Google Scholar]
53. Lee H, Goetzl EJ, An SLysophosphatidic acid and sphingosine 1-phosphate stimulate endothelial cell wound healing. Am J Physiol. 2000;278:C612–C618.[PubMed][Google Scholar]
54. Muraki K, Imaizumi YA novel function of sphingosine 1-phosphate to activate a non-selective cation channel in human endothelial cells. J Physiol. 2001;537:431–441.[Google Scholar]
55. McCabe TJ, Fulton D, Roman LJ, Sessa WCEnhanced electron flux and reduced calmodulin dissociation may explain ‘calcium-independent’ eNOS activation by phosphorylation. J Biol Chem. 2000;275:6123–6128.[PubMed][Google Scholar]
56. Gonzalez E, Kou R, Michel TRac1 modulates sphingosine 1-phosphate-mediated activation of phosphoinositide 3-kinase/Akt signaling pathways in vascular endothelial cells. J Biol Chem. 2006;281:3210–3216.[PubMed][Google Scholar]
57. Igarashi J, Michel TMore sweetness than light? A search for the causes of diabetic vasculopathy. J Clin Invest. 2001;108:1425–1427.[Google Scholar]
58. Fulton D, Ruan L, Sood SG, Li C, Zhang Q, Venema RC. Agonist-stimulated endothelial nitric oxide synthase activation and vascular relaxation. Role of eNOS phosphorylation at Tyr83. Circ Res. 2008;102:497–504.[PubMed]
59. Coussin F, Scott RH, Wise A, Nixon GFComparison of sphingosine 1-phosphate-induced intracellular signaling pathways in vascular smooth muscles: differential role in vasoconstriction. Circ Res. 2002;91:151–157.[PubMed][Google Scholar]
60. Salomone S, Potts EM, Tyndall S, Ip PC, Chun J, Brinkmann V, et al Analysis of sphingosine 1-phosphate receptors involved in constriction of isolated cerebral arteries with receptor null mice and pharmacological tools. Br J Pharmacol. 2008;153:140–147.[Google Scholar]
61. Lorenz JN, Arend LJ, Robitz R, Paul RJ, MacLennan AJVascular dysfunction in S1P₂ sphingosine 1-phosphate receptor knockout mice. Am J Physiol Regul Integr Comp Physiol. 2007;292:R440–R446.[PubMed][Google Scholar]
62. Kluk MJ, Hla TRole of the sphingosine 1-phosphate receptor EDG-1 in vascular smooth muscle cell proliferation and migration. Circ Res. 2001;89:496–502.[PubMed][Google Scholar]
63. Wamhoff BR, Lynch KR, Macdonald TL, Owens GKSphingosine-1-phosphate receptor subtypes differentially regulate smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol. 2008;28:1454–1461.[Google Scholar]
64. Zhou H, Murthy KSDistinctive G protein-dependent signaling in smooth muscle by sphingosine 1-phosphate receptors S1P₁ and S1P₂. Am J Physiol Cell Physiol. 2004;286:C1130–C1138.[PubMed][Google Scholar]
65. Rosenfeldt HM, Amrani Y, Watterson KR, Murthy KS, Panettieri RA, Jr, Spiegel SSphingosine-1-phosphate stimulates contraction of human airway smooth muscle cells. FASEB J. 2003;17:1789–1799.[PubMed][Google Scholar]
66. Somlyo AP, Somlyo AVCa^{sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase.}Physiol Rev. 2003;83:1325–1358.[PubMed][Google Scholar]
67. Sanders KMInvited review: mechanisms of calcium handling in smooth muscles. J Appl Physiol. 2001;91:1438–1449.[PubMed][Google Scholar]
68. McFadzean I, Gibson AThe developing relationship between receptor-operated and store-operated calcium channels in smooth muscle. Br J Pharmacol. 2002;135:1–13.[Google Scholar]
69. Bischoff A, Czyborra P, Fetscher C, Meyer Zu Heringdorf D, Jakobs KH, et al Sphingosine-1-phosphate and sphingosylphosphorylcholine constrict renal and mesenteric microvessels in vitro. Br J Pharmacol. 2000;130:1871–1877.[Google Scholar]
70. Ohmori T, Yatomi Y, Osada M, Kazama F, Takafuta T, Ikeda H, et al Sphingosine 1-phosphate induces contraction of coronary artery smooth muscle cells via S1P₂. Cardiovasc Res. 2003;58:170–177.[PubMed][Google Scholar]
71. Tosaka M, Okajima F, Hashiba Y, Saito N, Nagano T, Watanabe T, et al Sphingosine 1-phosphate contracts canine basilar arteries in vitro and in vivo: possible role in pathogenesis of cerebral vasospasm. Stroke. 2001;32:2913–2919.[PubMed][Google Scholar]
72. Bolz SS, Vogel L, Sollinger D, Derwand R, de Wit C, Loirand G, et al Nitric oxide-induced decrease in calcium sensitivity of resistance arteries is attributable to activation of the myosin light chain phosphatase and antagonized by the RhoA/Rho kinase pathway. Circulation. 2003;107:3081–3087.[PubMed][Google Scholar]
73. Hardin CD, Vallejo JCaveolins in vascular smooth muscle: form organizing function. Cardiovasc Res. 2006;69:808–815.[Google Scholar]
74. Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, et al Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science. 2002;296:346–349.[PubMed][Google Scholar]
75. Tolle M, Levkau B, Keul P, Brinkmann V, Giebing G, Schonfelder G, et al Immunomodulator FTY720 induces eNOS-dependent arterial vasodilatation via the lysophospholipid receptor S1P₃. Circ Res. 2005;96:913–920.[PubMed][Google Scholar]
76. Hemmings DG, Xu Y, Davidge STSphingosine 1-phosphate-induced vasoconstriction is elevated in mesenteric resistance arteries from aged female rats. Br J Pharmacol. 2004;143:276–284.[Google Scholar]
77. Alewijnse AE, Peters SL, Michel MCCardiovascular effects of sphingosine-1-phosphate and other sphingomyelin metabolites. Br J Pharmacol. 2004;143:666–684.[Google Scholar]
78. Salomone S, Yoshimura S, Reuter U, Foley M, Thomas SS, Moskowitz MA, et al S1P₃ receptors mediate the potent constriction of cerebral arteries by sphingosine-1-phosphate. Eur J Pharmacol. 2003;469:125–134.[PubMed][Google Scholar]
79. Hemmings DG, Hudson NK, Halliday D, O’Hara M, Baker PN, Davidge ST, et al Sphingosine-1-phosphate acts via rho-associated kinase and nitric oxide to regulate human placental vascular tone. Biol Reprod. 2006;74:88–94.[PubMed][Google Scholar]
80. Russo G, Leopold JA, Loscalzo JVasoactive substances: nitric oxide and endothelial dysfunction in atherosclerosis. Vascul Pharmacol. 2002;38:259–269.[PubMed][Google Scholar]
81. Loscalzo JNitric oxide insufficiency, platelet activation, and arterial thrombosis. Circ Res. 2001;88:756–762.[PubMed][Google Scholar]
82. McVerry BJ, Garcia JG. In vitro and in vivo modulation of vascular barrier integrity by sphingosine 1-phosphate: mechanistic insights. Cell Signal. 2005;17:131–139.[PubMed]
83. Kume N, Gimbrone MAJLysophosphatidylcholine transcriptionally induces growth factor gene expression in cultured human endothelial cells. J Clin Invest. 1994;93:907–911.[Google Scholar]
84. Maschberger P, Bauer M, Baumann-Siemons J, Zangl KJ, Negrescu EV, Reininger AJ, et al Mildly oxidized low density lipoprotein rapidly stimulates via activation of the lysophosphatidic acid receptor Src family and Syk tyrosine kinases and Ca^{influx in human platelets.}J Biol Chem. 2000;275:19159–19166.[PubMed][Google Scholar]