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Thromb Haemost 2009; 101(04): 665-673
DOI: 10.1160/TH08-10-0675
Review Article
Schattauer GmbH

Sphingosine-1-phosphate: A bioactive lipid that confers high-density lipoprotein with vasculoprotection mediated by nitric oxide and prostacyclin

Cristina Rodríguez   *
,
María González-Díez   *
,
Lina Badimon
1   Centro de Investigación Cardiovascular (CSIC-ICCC), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
José Martínez-González
1   Centro de Investigación Cardiovascular (CSIC-ICCC), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
› Author Affiliations
Further Information

Publication History

Received: 17 October 2008

Accepted after minor revision: 21 January 2009

Publication Date:
23 November 2017 (online)

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Summary

Sphingosine-1-phosphate (S1P) is a bioactive lipid generated in the intracellular membranes from the metabolism of sphingomyelin. Once secreted/exported by cells of haematopoietic origin and vascular cells S1P interacts with plasma proteins and accumulates in high-density lipoprotein (HDL). Growing evidence indicates that HDL-associated S1P is responsible for the beneficial effects of these lipoproteins on vasorelaxation, cell survival, cell adhesiveness, angiogenesis and synthesis of two powerful endogenous anti-atherogenic and anti-thrombotic molecules such as nitric oxide (NO) and prostacyclin (PGI2). It is likely that vascular effects of HDL-S1P are regulated by the local expression of S1P receptors. Five G protein-coupled receptors (S1P1 to S1P5), with differential expression patterns and dissimilar coupling mechanism to G protein subunits, have been identified in the vasculature. This review is focused on the central role of S1P as a bioactive component that confers vasculoprotective properties to HDL by eliciting a wide range of biological responses on endothelial and smooth muscle cells largely dependent on the up-regulation of NO and prostacyclin.

Keywords

High-density lipoproteins - sphingosine-1-phosphate - prostacyclin - nitric oxide - vascular function

* These authors contributed equally.


 

  • References

  • 1 Yatomi Y, Ozaki Y, Ohmori T. et al. Sphingosine 1-phosphate: synthesis and release. Prostaglandins Other Lipid Mediat 2001; 64: 107-122.
    CrossrefPubMedGoogle Scholar
  • 2 Hänel P, Andréani P, Gräler MH. Erythrocytes store and release sphingosine 1-phosphate in blood. FASEB J 2007; 21: 1202-1209.
    CrossrefPubMedGoogle Scholar
  • 3 Venkataraman K, Lee YM, Michaud J. et al. Vascular endothelium as a contributor of plasma sphingosine 1-phosphate. Circ Res 2008; 102: 669-676.
    CrossrefPubMedGoogle Scholar
  • 4 Mitra P, Oskeritzian CA, Payne SG. et al. Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc Natl Acad Sci USA 2006; 103: 16394-16399.
    CrossrefPubMedGoogle Scholar
  • 5 Okajima F. Plasma 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.
    CrossrefPubMedGoogle Scholar
  • 6 Rhoads GG, Gulbrandsen CL, Kagan A. Serum lipoproteins and coronary heart disease in a population study of Hawaii Japanese men. N Engl J Med 1976; 294: 293-298.
    CrossrefPubMedGoogle Scholar
  • 7 Badimon JJ, Badimon L, Galvez A. et al. High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits. Lab Invest 1989; 60: 455-461.
    PubMedGoogle Scholar
  • 8 Badimon JJ, Badimon L, Fuster V. Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit. J Clin Invest 1990; 85: 1234-1241.
    CrossrefPubMedGoogle Scholar
  • 9 Ibanez B, Vilahur G, Cimmino G. et al. Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis. J Am Coll Cardiol 2008; 51: 1104-1109.
    CrossrefPubMedGoogle Scholar
  • 10 Assmann G, Nofer JR. Atheroprotective effects of high-density lipoproteins. Annu Rev Med 2003; 54: 321-341.
    CrossrefPubMedGoogle Scholar
  • 11 Mineo C, Deguchi H, Griffin JH, Shaul PW. Endothelial and antithrombotic actions of HDL. Circ Res 2006; 98: 1352-1364.
    CrossrefPubMedGoogle Scholar
  • 12 Barter PJ, Puranik R, Rye KA. New insights into the role of HDL as an anti-inflammatory agent in the prevention of cardiovascular disease. Curr Cardiol Rep 2007; 9: 493-498.
    CrossrefPubMedGoogle Scholar
  • 13 Spiegel S, Milstien S. Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 2003; 4: 397-407.
    CrossrefPubMedGoogle Scholar
  • 14 Nofer JR, van der Giet M, Tölle M. et al. HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J Clin Invest 2004; 113: 569-581.
    CrossrefPubMedGoogle Scholar
  • 15 Miura S, Fujino M, Matsuo Y. et al. High density lipoprotein-induced angiogenesis requires the activation of Ras/MAP kinase in human coronary artery endothelial cells. Arterioscler Thromb Vasc Biol 2003; 23: 802-808.
    CrossrefPubMedGoogle Scholar
  • 16 von Otte S, Paletta JR, Becker S. et al. Follicular fluid high density lipoprotein-associated sphingosine 1-phosphate is a novel mediator of ovarian angiogenesis. J Biol Chem 2006; 281: 5398-5405.
    CrossrefPubMedGoogle Scholar
  • 17 Nofer JR, Bot M, Brodde M. et al. FTY720, a synthetic sphingosine 1 phosphate analogue, inhibits development of atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation 2007; 115: 501-508.
    CrossrefPubMedGoogle Scholar
  • 18 Theilmeier G, Schmidt C, Herrmann J. 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.
    CrossrefPubMedGoogle Scholar
  • 19 Alewijnse AE, Peters SL. Sphingolipid signalling in the cardiovascular system: good, bad or both?. Eur J Pharmacol 2008; 585: 292-302.
    CrossrefPubMedGoogle Scholar
  • 20 Yatomi Y. Sphingosine 1-phosphate in vascular biology: possible therapeutic strategies to control vascular diseases. Curr Pharm Des 2006; 12: 575-587.
    CrossrefPubMedGoogle Scholar
  • 21 Keul P, Tölle M, Lucke S. et al. The sphingosine-1-phosphate analogue FTY720 reduces atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2007; 27: 607-613.
    CrossrefPubMedGoogle Scholar
  • 22 Martínez-González J, Badimon L. Influence of statin use on endothelial function: from bench to clinics. Curr Pharm Des 2007; 13: 1771-1786.
    CrossrefPubMedGoogle Scholar
  • 23 Igarashi J, Miyoshi M, Hashimoto T. et al. Statins induce S1P1 receptors and enhance endothelial nitric oxide production in response to high-density lipoproteins. Br J Pharmacol 2007; 150: 470-479.
    PubMedGoogle Scholar
  • 24 González-Díez M, Rodríguez C, Badimon L, Martínez-González J. Prostacyclin induction by high-density lipoprotein (HDL) in vascular smooth muscle cells depends on sphingosine 1-phosphate receptors: effect of simvastatin. Thromb Haemost 2008; 100: 119-126.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Pappu R, Schwab SR, Cornelissen I. et al. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 2007; 316: 295-298.
    CrossrefPubMedGoogle Scholar
  • 26 Ohkawa R, Nakamura K, Okubo S. et al. Plasma sphingosine-1-phosphate measurement in healthy subjects: close correlation with red blood cell parameters. Ann Clin Biochem 2008; 45: 356-363.
    CrossrefPubMedGoogle Scholar
  • 27 Hla T, Venkataraman K, Michaud J. The vascular S1P gradient-Cellular sources and biological significance. Biochim Biophys Acta 2008; 1781: 477-482.
    CrossrefPubMedGoogle Scholar
  • 28 Waeber C, Blondeau N, Salomone S. Vascular sphingosine-1-phosphate S1P1 and S1P3 receptors. Drug News Perspect 2004; 17: 365-382.
    CrossrefPubMedGoogle Scholar
  • 29 Kimura T, Watanabe T, Sato K. et al. Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3. Biochem J 2000; 348: 71-76.
    CrossrefPubMedGoogle Scholar
  • 30 Tamama K, Kon J, Sato K. et al. Extracellular mechanism through the Edg family of receptors might be responsible for sphingosine-1-phosphate-induced regulation of DNA synthesis and migration of rat aortic smooth-muscle cells. Biochem J 2001; 353: 139-146.
    CrossrefPubMedGoogle Scholar
  • 31 Mazurais D, Robert P, Gout B. et al. Cell type-specific localization of human cardiac S1P receptors. J Histochem Cytochem 2002; 50: 661-670.
    CrossrefPubMedGoogle Scholar
  • 32 Ryu Y, Takuwa N, Sugimoto N. et al. Sphingosine-1-phosphate, a platelet-derived lysophospholipid mediator, negatively regulates cellular Rac activity and cell migration in vascular smooth muscle cells. Circ Res 2002; 90: 325-332.
    CrossrefPubMedGoogle Scholar
  • 33 Damirin A, Tomura H, Komachi M. et al. Sphingo-sine 1-phosphate receptors mediate the lipid-induced cAMP accumulation through cyclooxygenase-2/pros-taglandin I2 pathway in human coronary artery smooth muscle cells. Mol Pharmacol 2005; 67: 1177-1185.
    CrossrefPubMedGoogle Scholar
  • 34 Michel MC, Mulders AC, Jongsma M. et al. Vascular effects of sphingolipids. Acta Paediatr Suppl 2007; 96: 44-48.
    PubMedGoogle Scholar
  • 35 Sensken SC, Stäubert C, Keul P. et al. Selective activation of G alpha i mediated signalling of S1P3 by FTY720-phosphate. Cell Signal 2008; 20: 1125-1133.
    CrossrefPubMedGoogle Scholar
  • 36 Yuhanna IS, Zhu Y, Cox BE. et al. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med 2001; 7: 853-857.
    CrossrefPubMedGoogle Scholar
  • 37 Mineo C, Yuhanna IS, Quon MJ, Shaul PW. High density lipoprotein-induced endothelial nitric-oxide synthase activation is mediated by Akt and MAP kinases. J Biol Chem 2003; 278: 9142-9149.
    CrossrefPubMedGoogle Scholar
  • 38 Rämet ME, Rämet M, Lu Q. et al. High-density lipoprotein increases the abundance of eNOS protein in human vascular endothelial cells by increasing its half-life. J Am Coll Cardiol 2003; 41: 2288-2297.
    CrossrefPubMedGoogle Scholar
  • 39 Tölle M, Levkau B, Keul P. et al. Immunomodulator FTY720 Induces eNOS-dependent arterial vasodilatation via the lysophospholipid receptor S1P3. Circ Res 2005; 96: 913-920.
    CrossrefPubMedGoogle Scholar
  • 40 Igarashi J, Michel T. Agonist-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.
    CrossrefPubMedGoogle Scholar
  • 41 Roviezzo F, Bucci M, Delisle C. et al. Essential requirement for sphingosine kinase activity in eNOS-dependent NO release and vasorelaxation. FASEB J 2006; 20: 340-342.
    CrossrefPubMedGoogle Scholar
  • 42 Viñals M, Martinez-Gonzalez J, Badimon JJ. et al. HDL-induced prostacyclin release in smooth muscle cells is dependent on cyclooxygenase-2 (Cox-2). Arterioscler Thromb Vasc Biol 1997; 17: 3481-3488.
    CrossrefPubMedGoogle Scholar
  • 43 Viñals M, Martinez-Gonzalez J, Badimon L. Regulatory effects of HDL on smooth muscle cell prostacyclin release. Arterioscler Thromb Vasc Biol 1999; 19: 2405-2411.
    CrossrefPubMedGoogle Scholar
  • 44 Cockerill GW, Saklatvala J, Ridley SH. et al. High-density lipoproteins differentially modulate cytokine-induced expression of E-selectin and cyclooxygenase-2. Arterioscler Thromb Vasc Biol 1999; 19: 910-917.
    CrossrefPubMedGoogle Scholar
  • 45 Norata GD, Callegari E, Inoue H, Catapano AL. HDL3 induces cyclooxygenase-2 expression and pros-tacyclin release in human endothelial cells via a p38 MAPK/CRE-dependent pathway: effects on COX-2/PGI-synthase coupling. Arterioscler Thromb Vasc Biol 2004; 24: 871-877.
    CrossrefPubMedGoogle Scholar
  • 46 Escudero I, Martínez-González J, Alonso R. et al. Experimental and interventional dietary study in humans on the role of HDL fatty acid composition in PGI2 release and Cox-2 expression by VSMC. Eur J Clin Invest 2003; 33: 779-786.
    CrossrefPubMedGoogle Scholar
  • 47 Martínez-González J, Badimon L. Mechanisms underlying the cardiovascular effects of COX-inhibition: benefits and risks. Curr Pharm Des 2007; 13: 2215-2227.
    CrossrefPubMedGoogle Scholar
  • 48 Topper JN, Cai J, Falb D, Gimbrone Jr MA. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli. Proc Natl Acad Sci USA 1996; 93: 10417-10422.
    CrossrefPubMedGoogle Scholar
  • 49 Martínez-González J, Escudero I, Badimon L. Simvastatin potenciates PGI2 release induced by HDL in human VSMC: effect on Cox-2 up-regulation and MAPK signalling pathways activated by HDL. Atherosclerosis 2004; 174: 305-313.
    CrossrefPubMedGoogle Scholar
  • 50 Ohmori T, Yatomi Y, Osada M. et al. Sphingosine 1-phosphate induces contraction of coronary artery smooth muscle cells via S1P2. Cardiovasc Res 2003; 58: 170-177.
    CrossrefPubMedGoogle Scholar
  • 51 Salomone S, Potts EM, Tyndall S. 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.
    CrossrefPubMedGoogle Scholar
  • 52 Cockerill GW, Rye KA, Gamble JR. et al. High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol 1995; 15: 1987-1994.
    CrossrefPubMedGoogle Scholar
  • 53 Schmidt A, Geigenmüller S, Völker W, Buddecke E. The antiatherogenic and antiinflammatory effect of HDL-associated lysosphingolipids operates via Akt -->NF-kappaB signalling pathways in human vascular endothelial cells. Basic Res Cardiol 2006; 101: 109-116.
    CrossrefPubMedGoogle Scholar
  • 54 Kimura T, Tomura H, Mogi C. et al. Role of scavenger receptor class B type I and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells. J Biol Chem 2006; 281: 37457-37467.
    CrossrefPubMedGoogle Scholar
  • 55 Lee H, Lin CI, Liao JJ. et al. Lysophospholipids increase ICAM-1 expression in HUVEC through a Giand NF-kappaB-dependent mechanism. Am J Physiol Cell Physiol 2004; 287: C1657-1666.
    CrossrefPubMedGoogle Scholar
  • 56 Xia P, Vadas MA, Rye KA. et al. High density lipo-proteins (HDL) interrupt the sphingosine kinase signalling pathway. A possible mechanism for protection against atherosclerosis by HDL. J Biol Chem 1999; 274: 33143-33147.
    CrossrefPubMedGoogle Scholar
  • 57 Kase H, Hattori Y, Jojima T. et al. Globular adiponectin induces adhesion molecule expression through the sphingosine kinase pathway in vascular endothelial cells. Life Sci 2007; 81: 939-943.
    CrossrefPubMedGoogle Scholar
  • 58 Kimura T, Tomura H, Mogi C. et al. Sphingosine 1-phosphate receptors mediate stimulatory and inhibitory signalings for expression of adhesion molecules in endothelial cells. Cell Signal 2006; 18: 841-850.
    CrossrefPubMedGoogle Scholar
  • 59 Whetzel AM, Bolick DT, Srinivasan S. et al. Sphingosine-1 phosphate prevents monocyte/endothelial interactions in type 1 diabetic NOD mice through activation of the S1P1 receptor. Circ Res 2006; 99: 731-739.
    CrossrefPubMedGoogle Scholar
  • 60 Tani M, Kawakami A, Nagai M. et al. Sphingosine 1-phosphate (S1P) inhibits monocyte-endothelial cell interaction by regulating of RhoA activity. FEBS Lett 2007; 581: 4621-4626.
    CrossrefPubMedGoogle Scholar
  • 61 Aoki S, Yatomi Y, Shimosawa T. et al. The suppressive effect of sphingosine 1-phosphate on monocyte-endothelium adhesion may be mediated by the rearrangement of the endothelial integrins alpha(5)beta(1) and alpha(v)beta(3). J Thromb Haemost 2007; 5: 1292-1301.
    CrossrefPubMedGoogle Scholar
  • 62 Nofer JR, Levkau B, Wolinska I. et al. Suppression of endothelial cell apoptosis by high density lipoproteins (HDL) and HDL-associated lysosphingolipids. J Biol Chem 2001; 276: 34480-34485.
    CrossrefPubMedGoogle Scholar
  • 63 Kwon YG, Min JK, Kim KM. et al. Sphingosine 1-phosphate protects human umbilical vein endothelial cells from serum-deprived apoptosis by nitric oxide production. J Biol Chem 2001; 276: 10627-10633.
    CrossrefPubMedGoogle Scholar
  • 64 Kimura T, Sato K, Kuwabara A. et al. Sphingosine 1-phosphate may be a major component of plasma lipo-proteins responsible for the cytoprotective actions in human umbilical vein endothelial cells. J Biol Chem 2001; 276: 31780-31785.
    CrossrefPubMedGoogle Scholar
  • 65 Kontush A, Therond P, Zerrad A. et al. Preferential sphingosine-1-phosphate enrichment and sphingomyelin depletion are key features of small dense HDL3 particles: relevance to antiapoptotic and antioxidative activities. Arterioscler Thromb Vasc Biol 2007; 27: 1843-1849.
    CrossrefPubMedGoogle Scholar
  • 66 Mihovilovic M, Robinette JB, DeKroon RM. et al. High-fat/high-cholesterol diet promotes a S1P receptor-mediated antiapoptotic activity for VLDL. J Lipid Res 2007; 48: 806-815.
    CrossrefPubMedGoogle Scholar
  • 67 Lee OH, Kim YM, Lee YM. et al. Sphingosine 1-phosphate induces angiogenesis: its angiogenic action and signalling mechanism in human umbilical vein endothelial cells. Biochem Biophys Res Commun 1999; 264: 743-750.
    CrossrefPubMedGoogle Scholar
  • 68 English D, Welch Z, Kovala AT. et al. Sphingosine 1-phosphate released from platelets during clotting accounts for the potent endothelial cell chemotactic activity of blood serum and provides a novel link between hemostasis and angiogenesis. FASEB J 2000; 14: 2255-2265.
    CrossrefPubMedGoogle Scholar
  • 69 Rikitake Y, Hirata K, Kawashima S. et al. Involvement of endothelial nitric oxide in sphingosine-1-phosphate-induced angiogenesis. Arterioscler Thromb Vasc Biol 2002; 22: 108-114.
    CrossrefPubMedGoogle Scholar
  • 70 Igarashi J, Erwin PA, Dantas AP. et al. VEGF 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.
    CrossrefPubMedGoogle Scholar
  • 71 Kimura T, Sato K, Malchinkhuu E. et al. High-density lipoprotein stimulates endothelial cell migration and survival through sphingosine 1-phosphate and its receptors. Arterioscler Thromb Vasc Biol 2003; 23: 1283-1288.
    CrossrefPubMedGoogle Scholar
  • 72 Miura S, Tanigawa H, Matsuo Y. et al. Ras/Raf1-dependent signal in sphingosine-1-phosphate-induced tube formation in human coronary artery endothelial cells. Biochem Biophys Res Commun 2003; 306: 924-929.
    CrossrefPubMedGoogle Scholar
  • 73 Matsuo Y, Miura S, Kawamura A. et al. Newly developed reconstituted high-density lipoprotein containing sphingosine-1-phosphate induces endothelial tube formation. Atherosclerosis 2007; 194: 159-168.
    CrossrefPubMedGoogle Scholar
  • 74 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.
    CrossrefPubMedGoogle Scholar
  • 75 Lee JF, Zeng Q, Ozaki H. et al. Dual roles of tight junction-associated protein, zonula occludens-1, in sphingosine 1-phosphate-mediated endothelial chemo-taxis and barrier integrity. J Biol Chem 2006; 281: 29190-29200.
    CrossrefPubMedGoogle Scholar
  • 76 Xu M, Waters CL, Hu C. et al. Sphingosine 1-phosphate rapidly increases endothelial barrier function independently of VE-cadherin but requires cell spreading and Rho kinase. Am J Physiol Cell Physiol 2007; 293: C1309-1318.
    CrossrefPubMedGoogle Scholar
  • 77 Argraves KM, Gazzolo PJ, Groh EM. et al. HDL-associated sphingosine-1-phosphate promotes endothelial barrier function. J Biol Chem 2008; 25074-25081.
    PubMedGoogle Scholar
  • 78 Noor R, Shuaib U, Wang CX. et al. High-density lipoprotein cholesterol regulates endothelial progenitor cells by increasing eNOS and preventing apoptosis. Atherosclerosis 2007; 192: 92-99.
    CrossrefPubMedGoogle Scholar
  • 79 Tso C, Martinic G, Fan WH. et al. High-density lipoproteins enhance progenitor-mediated endothelium repair in mice. Arterioscler Thromb Vasc Biol 2006; 26: 1144-1149.
    CrossrefPubMedGoogle Scholar
  • 80 Petoumenos V, Nickenig G, Werner N. High density lipoprotein exerts vasculoprotection via endothelial progenitor cells. J Cell Mol Med. 2008 Aug 14; epub ahead of print.
    PubMedGoogle Scholar
  • 81 Kimura T, Boehmler AM, Seitz G. et al. The sphingosine 1-phosphate receptor agonist FTY720 supports CXCR4-dependent migration and bone marrow homing of human CD34+ progenitor cells. Blood 2004; 103: 4478-4486.
    CrossrefPubMedGoogle Scholar
  • 82 Walter DH, Rochwalsky U, Reinhold J. et al. Sphingosine-1-phosphate stimulates the functional capacity of progenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor. Arterioscler Thromb Vasc Biol 2007; 27: 275-282.
    PubMedGoogle Scholar
  • 83 Tamama K, Tomura H, Sato K. et al. High-density lipoprotein inhibits migration of vascular smooth muscle cells through its sphingosine 1-phosphate component. Atherosclerosis 2005; 178: 19-23.
    CrossrefPubMedGoogle Scholar
  • 84 Damirin A, Tomura H, Komachi M. et al. Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells. Am J Physiol Heart Circ Physiol 2007; 292: H2513-2522.
    CrossrefPubMedGoogle Scholar
  • 85 Hobson JP, Rosenfeldt HM, Barak LS. et al. Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science 2001; 291: 1800-1803.
    CrossrefPubMedGoogle Scholar
  • 86 Lockman K, Hinson JS, Medlin MD. et al. Sphingosine 1-phosphate stimulates smooth muscle cell differentiation and proliferation by activating separate serum response factor co-factors. J Biol Chem 2004; 279: 42422-42430.
    CrossrefPubMedGoogle Scholar
  • 87 Kluk MJ, Hla T. Role of the sphingosine 1-phosphate receptor EDG-1 in vascular smooth muscle cell proliferation and migration. Circ Res 2001; 89: 496-502.
    CrossrefPubMedGoogle Scholar
  • 88 Takuwa Y. Subtype-specific differential regulation of Rho family G proteins and cell migration by the Edg family sphingosine-1-phosphate receptors. Biochim Biophys Acta 2002; 1582: 112-120.
    CrossrefPubMedGoogle Scholar
  • 89 Tölle M, Pawlak A, Schuchardt M. et al. HDL-associated lysosphingolipids inhibit NAD(P)H oxidase-dependent monocyte chemoattractant protein-1 production. Arterioscler Thromb Vasc Biol 2008; 28: 1542-1548.
    CrossrefPubMedGoogle Scholar
  • 90 Kothapalli D, Fuki I, Ali K. et al. Antimitogenic effects of HDL and APOE mediated by Cox-2-dependent IP activation. J Clin Invest 2004; 113: 609-618.
    CrossrefPubMedGoogle Scholar
  • 91 Duong CQ, Bared SM, Abu-Khader A. et al. Expression of the lysophospholipid receptor family and investigation of lysophospholipid-mediated responses in human macrophages. Biochim Biophys Acta 2004; 1682: 112-119.
    CrossrefPubMedGoogle Scholar
  • 92 Peng X, Hassoun PM, Sammani S. et al. Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury. Am J Respir Crit Care Med 2004; 169: 1245-1251.
    CrossrefPubMedGoogle Scholar
  • 93 Dueñas AI, Aceves M, Fernández-Pisonero I. et al. Selective attenuation of Toll-like receptor 2 signalling may explain the atheroprotective effect of sphingosine 1-phosphate. Cardiovasc Res 2008; 79: 537-544.
    CrossrefPubMedGoogle Scholar
  • 94 Hughes JE, Srinivasan S, Lynch KR. et al. Sphingo-sine-1-phosphate induces an antiinflammatory pheno-type in macrophages. Circ Res 2008; 102: 950-958.
    CrossrefPubMedGoogle Scholar
  • 95 Nissen SE, Tardif JC, Nicholls SJ. et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 2007; 356: 1304-1316.
    CrossrefPubMedGoogle Scholar