Prostacyclin induction by high-density lipoprotein (HDL) in vascular smooth muscle cells depends on sphingosine 1-phosphate receptors: Effect of simvastatin

María González-Díez; Cristina Rodríguez; Lina Badimon; José Martínez-González

doi:10.1160/TH07-11-0675

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(01): 119-126
DOI: 10.1160/TH07-11-0675

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Prostacyclin induction by high-density lipoprotein (HDL) in vascular smooth muscle cells depends on sphingosine 1-phosphate receptors: Effect of simvastatin

María González-Díez

¹Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

,

Cristina Rodríguez

¹Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

,

Lina Badimon

¹Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

,

José Martínez-González

¹Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

› Author Affiliations

Abstract

Summary

Prostacyclin (PGI2) is an important regulator of vascular homeostasis. Our goal was to analyze the role of sphingosine 1-phosphate (S1P) and its receptors in the up-regulation of cyclooxygenase-2 (Cox-2) induced by HDL in human vascular smooth muscle cells (VSMC). S1P induces Cox-2 expression in a time-and dose-dependent manner at concentrations (0.02–1 µM) compatible with those present in physiological HDL levels. The effect was mimicked by dihydro-S1P (DhS1P), a S1P derivative that only acts through cell surface S1P receptors. Desensitiz-ation of S1P receptors with S1P (or DhS1P) abolished HDL-induced Cox-2 up-regulation and PGI2 release. Inhibition of S1P receptors by suramin (inhibitor of S1P3), JTE013 (inhibitor of S1P2) or VPC23019 (inhibitor of S1P1 and S1P3) reduced the up-regulation of Cox-2 induced by HDL and S1P. The combination of suramin and JTE013 increased the inhibitory effect compared to that observed in cells treated with each inhibitor alone. siRNA against S1P2 or S1P3 significantly reduced the ability of HDL and S1P to up-regulate Cox-2. Simvastatin induced over-expression of S1P3 and potentiated the induction of Cox-2 expression produced by HDL (or S1P). Finally, suramin, JTE013 and VPC23019 inhibited p38 MAPK and ERK1/2 signaling pathways activated by HDL (or S1P) and the downstream activation of CREB, a key transcription factor involved in Cox-2 transcriptional up-regulation. These results indicate that S1P receptors, in particular S1P2 and S1P3, are involved in the Cox-2-dependent effects of HDL on vascular cells. Strategies aimed to therapeutically modulate S1P or S1P receptors could be useful to improve cardiovascular protection.

Keywords

Atherothrombosis - smooth muscle cells - lipoproteins - gene expression - antiplatelet agents

Full Text

References

References
1 Assmann G, Nofer JR. Atheroprotective effects of high-density lipoproteins. Annu Rev Med 2003; 54: 321-341.
2 Badimon JJ, Badimon L, Galvez A. et al. HDL plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits. Lab Invest 1989; 60: 455-461.
3 Badimon JJ, Badimon L, Fuster V. Regression of atherosclerotic lesions by HDL plasma fraction in the cholesterol-fed rabbit. J Clin Invest 1990; 85: 1234-1241.
4 Mineo C, Deguchi H, Griffin JH. et al. Endothelial and antithrombotic actions of HDL. Circ Res 2006; 98: 1352-1364.
5 Viñals M, Martínez-González J, Badimon L. HDL-Induced Prostacyclin release in smooth muscle cells is dependent on cyclooxygenase-2 (Cox-2). Arterioscler Thromb Vasc Biol 1997; 17: 3481-3488.
6 Vinals M, Martinez-Gonzalez J, Badimon L. Regulatory effects of HDL on smooth muscle cell prostacyclin release. Arterioscler Thromb Vasc Biol 1999; 19: 2405-2411.
7 Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest 2006; 116: 4-15.
8 Martinez-Gonzalez J, Badimon L. Mechanisms underlying the cardiovascular effects of Cox-inhibition: benefits and risks. Curr Pharm Des 2007; 13: 2215-2227.
9 Schrör K, Weber AA. COX-2 inhibitors and the thrombotic risk. Thromb Haemost 2006; 96: 391-392.
10 Escudero I, Martinez-Gonzalez J, Alonso R. et al. Experimental and interventional dietary study in humansonthe role ofHDL fatty acid composition in PGI₂ release and Cox-2 expression by VSMC. Eur J Clin Invest 2003; 33: 779-786.
11 Martinez-Gonzalez J, Escudero I, Badimon L. Sim-vastatin potentiates PGI₂ release induced by HDL in human VSMC: effect on Cox-2 up-regulation and MAPK signaling pathways activated by HDL. Atherosclerosis 2004; 174: 305-313.
12 Cockerill GW, Saklatvala J, Ridley SH. et al. HDL differentially modulate cytokine-induced expression of E-selectin and cyclooxygenase-2. Arterioscler Thromb Va sc Biol 1999; 19: 910-917.
13 Kimura T, Sato K, Kuwabara A. et al. Sphingosine 1-phosphate may bea major component of plasma lipo-proteins responsible for the cytoprotective actions in human umbilical vein endothelial cells. J Biol Chem 2001; 276: 31780-31785.
14 Sachinidis A, Kettenhofen R, Seewald S. et al. Evidence that lipoproteins are carriers of bioactive factors. Arterioscler Thromb Va sc Biol 1999; 19: 2412-2421.
15 Waeber C, Blondeau N, Salomone S. Va scular sphingosine-1-phosphate S1P1 and S1P3 receptors. Drug News Perspect 2004; 17: 365-382.
16 Spiegel S. Sphingosine 1-phosphate: a ligand for the EDG-1 family of G-protein-coupled receptors. Ann NY Acad Sci 2000; 905: 54-60.
17 Nofer JR, Levkau B, Wolinska I. et al. Suppression of endothelial cell apoptosis by HDL and HDL-associated lysosphingolipids. J Biol Chem 2001; 276: 34480-34485.
18 Kimura T, Sato K, Malchinkhuu E. et al. HDL stimulates endothelial cell migration and survival through sphingosine 1-phosphate and its receptors. Arterioscler Thromb Va sc Biol 2003; 23: 1283-1288.
19 Nofer JR, van der Giet M, Tolle M. et al. HDL induces NO-dependentvasorelaxation via the lysophospholipid receptor S1P3. J Clin Invest 2004; 113: 569-581.
20 Nofer JR, Junker R, Pulawski E. et al. High density lipoproteins induce cell cycle entry in vascular smooth muscle cells via mitogen activated protein kinase-dependent pathway. Thromb Haemost 2001; 85: 730-735.
21 von Otte S, Paletta JR, Becker S. et al. Follicular fluid HDL-associated sphingosine 1-phosphate is a novel mediator of ovarian angiogenesis. J Biol Chem 2006; 281: 5398-5405.
22 Martínez-González J, Viñals M, Vidal F. et al. Mevalonate deprivation impairs IGF-I/insulin signaling in human VSMC. Atherosclerosis 1997; 135: 213-223.
23 Tamama K, Tomura H, Sato K. et al. HDL inhibits migration of VSMC through its sphingosine 1-phosphate component. Atherosclerosis 2005; 178: 19-23.
24 Martorell L, Martínez-González J, Crespo J. et al. Neuron-derived orphan receptor-1 (NOR-1) is induced by thrombin and mediates vascular endothelial growth. J Thromb Haemost 2007; 05: 1766-1773.
25 Murata N, Sato K, Kon J. et al. Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions. Biochem J 2000; 352: 809-815.
26 Malchinkhuu E, Sato K, Muraki T. et al. Assessment of the role of sphingosine 1-phosphate and its receptors in HDL-induced stimulation of astroglial cell function. Biochem J 2003; 370: 817-827.
27 Van Brocklyn JR, Lee MJ, Menzeleev R. et al. Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled receptor Edg-1 and intracellular to regulate proliferation and survival. J Cell Biol 1998; 142: 229-240.
28 Ancellin N, Hla T. Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5. J Biol Chem 1999; 274: 18997-19002.
29 Damirin A, Tomura H, Komachi M. et al. Sphingosine 1-phosphate receptors mediate the lipid-induced cAMP accumulation through cyclooxygenase-2/prostaglandin I2 pathway in human coronary artery smooth muscle cells. Mol Pharmacol 2005; 67: 1177-1185.
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.
31 Davis MD, Clemens JJ, Macdonald TL. et al. Sphingosine 1-phosphate analogs as receptor antagonists. J Biol Chem 2005; 280: 9833-9841.
32 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. Arterioscler Thromb Vasc Biol 2004; 24: 871-877.
33 Martínez-González J, Rodríguez-Rodríguez R, González-Díez M. et al. Oleanolic acid induces pros-tacyclin release in human vascular smooth muscle cells through a cyclooxygenase-2-dependent mechanism. J Nutr 2008; 138: 443-448.
34 Kim JI, Jo EJ, Lee HY. et al. Sphingosine 1-phosphate in amniotic fluid modulates cyclooxygenase-2 expression in human amnion-derived WISH cells. J Biol Chem 2003; 278: 31731-31736.
35 Nodai A, Machida T, Izumi S. et al. Sphingosine 1-phosphate induces cyclooxygenase-2 via Ca2+-de-pendent, but MAPK-independent mechanism in rat vascular smooth muscle cells. Life Sci 2007; 80: 1768-1776.
36 Alfon J, Pueyo Palazon C, Royo T, Badimon L. Effects of statins in thrombosis and aortic lesion development in a dyslipemic rabbit model. Thromb Haemost 1999; 81: 822-827.
37 Casani L, Sanchez-Gomez S, Vilahur G, Badimon L. Pravastatin reduces thrombogenicity by mechanisms beyond plasma cholesterol lowering. Thromb Haemost 2005; 94: 1035-1041.
38 Martínez-González J, Badimon L. Influence of statin use on endothelial function: from bench to clinics. Curr Pharm Des 2007; 13: 1771-1786.
39 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.
40 Argraves KM, Argraves WS. HDL serves as an S1P signaling platform mediating a multitude of cardiovascular effects. J Lipid Res 2007; 48: 2325-2333.
41 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.
42 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.