Involvement of Cyclooxygenase- and Lipoxygenase-Mediated Conversion of Arachidonic Acid in Controlling Human Vascular Smooth Muscle Cell Proliferation

Herm-Jan M Brinkman; Marijke F van Buul-Worteiboer; Jan A van Mourik

doi:10.1055/s-0038-1645212

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1990; 63(02): 291-297
DOI: 10.1055/s-0038-1645212

Original Article

Schattauer GmbH Stuttgart

Involvement of Cyclooxygenase- and Lipoxygenase-Mediated Conversion of Arachidonic Acid in Controlling Human Vascular Smooth Muscle Cell Proliferation

Authors

Herm-Jan M Brinkman

The Central Laboratory of the Netherlands Red Cros Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands
Marijke F van Buul-Worteiboer

The Central Laboratory of the Netherlands Red Cros Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands
Jan A van Mourik

The Central Laboratory of the Netherlands Red Cros Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands

Abstract

PDF Download

Summary

We observed that the growth of human umbilical arterysmooth muscle cells was inhibited by the phospholipase A₂ inhibitors p-bromophenacylbromide and mepacrine. Thesefindings suggest that fatty acid metabolism might be integrated in the control mechanism of vascular smooth muscle cell proliferation. To identify eicosanoids possibly involved in this process, we studied both the metabolism of arachidonic acid of these cells in more detail and the effect of certain arachidonic acid metabolites on smooth muscle cells growth. We found no evidence for the conversion of arachidonic acid via the lipoxygenase pathway. In contrast, arachidonic acid was rapidly converted via the cyclooxy-genase pathway. The following metabolites were identified: prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F_1α (6-k-PGF_1α), prostaglandin F_2α (PGF_2α), 12-hydroxyheptadecatrienoic acid (12-HHT) and 11-hydroxyeicosatetetraenoic acid (11-HETE). PGE₂ was the major metabolite detected. Arachidonic acid metabolites were only found in the culture medium, not in the cell. After synthesis, 11-HETE was cleared from the culture medium. We have previously reported that PGE₂ inhibits the serum-induced [³H]-thymidine incorporation of growth-arrested human umbilical artery smooth muscle cells. Here we show that also 11-HETEexerts this inhibitory property. Thus, our data suggeststhat human umbilical artery smooth muscle cells convert arachidonic acid only via the cyclooxygenase pathway. Certain metabolites produced by this pathway, including PGE₂ and 11-HETE, may inhibit vascular smooth muscle cell proliferation.

PDF (390 kb)

References

References
1 Ross R. The pathogenesis of atherosclerosis, an update. New Engl J Med 1986; 314: 488-500
2 Spraragen SC, Bond VP, Dahl LK. Role of hyperplasia in vascular lesions of cholesterol-fed rabbits studied with thymidine-H³ autoradiography.. Circ Res 1962; 11: 329-336
3 Deuel TF, Huang JS. Platelet-derived growth factor: structure, function and roles in normal and transformed cells. J Clin Invest 1984; 74: 669-676
4 Libby P, Warner S JC, Friedman GB. Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest 1988; 81: 487-498
5 van Buul-Wortelboer MF, Brinkmann H JM, Dingemans KP, de Groot PhG, van Aken WG, van Mourik JA. Reconstitution of the vascular wall in vitro: a novel model to study interactions between endothelial and smooth muscle cells. Exp Cell Res 1986; 162: 151-158
6 Castellot JJ, Favreau LV, Karnovsky MJ, Rosenberg RD. Inhibition of vascular smooth muscle cell growth by endothelial cell-derived heparin. J Biol Chem 1982; 257: 11256-11260
7 de Groot PhD, Brinkman H JM, Gonzalves MD, van Mourik JA. The role of thrombin in the regulation of endothelial prostaglandin production. Biochim Biophys Acta 1985; 846: 342-349
8 Smith DL, Willis AL, Mahmud I. Eicosanoid effects on cell proliferation in vitro: Relevance to Atherosclerosis. Prostaglandins Leukotriens Med 1984; 16: 1-10
9 Huttner JJ, Gwebu ET, Panganamala RV. et al Fatty acids and their prostaglandin derivatives: inhibitor of proliferation in aortic smooth muscle cells. Science 1977; 197: 289-291
10 Loesberg C, van Wijk R, Zandbergen JJ, van Akcn WG, van Mourik JA, de Groot PhG. Cell cycle-dependent inhibition of human vascular smooth muscle cell proliferation by prostaglandin E₁ . Exp Cell Res 1985; 160: 117-125
11 Coughlin SR, Moskowitz MA, Zetter BR, Antoniades HN, Levine L. Platelet-dependent stimulation of prostacyclin synthesis by plateletderived growth factor. Nature 1980; 288: 600-602
12 Cornwell DG, Huttner JJ, Milo GE, Panganamala RV, Sharma HM, Geer JC. Polyunsaturated fatty acids, vitamin E and the proliferation of aortic smooth muscle cells. Lipids 1979; 14: 194-207
13 Bailey JM, Bryant RW, Low CE, Pupillo MB, Vanderhoek JY. Regulation of T-lymphocyte mitogenesis by the leukocyte product 15-hydroxy-eicosatetraenoic acid. Cell Immunol 1982; 67: 112-120
14 Setty B NY, Dubowy RL, Stuart MJ. Endothelial cell proliferation may be mediated via the production of endogenous lipoxygenase metabolites. Biochem Biophys Res Commun 1987; 144: 345-351
15 Hamberg M, Samuelsson B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc Natl Acad Sci USA 1974; 71: 3400-3404
16 Borgeat P, Samuelsson B. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci USA 1979; 76: 2148-2152
17 Turk J, Maas RL, Brash AR, Roberts J, Oates JA. Arachidonic acid 15-lipoxygenase products from human eosinophils. J Biol Chem 1982; 257: 7068-7076
18 Spector AA, Gordon JA, More SA. Hydroxyeicosatetraenoic acids (HETEs). Progr Lipid Res 1988; 27: 271-323
19 Hemler ME, Crawford CG, Lands W EM. Lipoxygenation activity of purified prostaglandin-forming cyclooxygenase. Biochemistry 1978; 17: 1772-1779
20 Porter NA, Wolf RA, Pagels WR, Marnett LJ. A test for the intermediacy of ll-hydroperoxyeicosa-5,8,12,14-tetraenoic acid (11-HPETE) in prostaglandin biosynthesis. Biochem Biophys Res Commun 1980; 92: 349-355
21 Nakao J, Ooyama T, Ito H, Ghang WC, Murota ST. Comparative effect of lipoxygenase products of arachidonic acid on rat aortic smooth muscle cell migration. Atherosclerosis 1982; 44: 339-342
22 Goetzl E, Woods JM, Gorman RR. Stimulation of human eosinophil and neutrophil polymorphonuclear leukocyte chemotaxis and random migration by 12-hvdroxy-5,8,10,14-eicosatetraenoic acid. J Clin Invest 1977; 59: 179-183
23 Stenson WF, Parker CW. Monohydroxyeicosatetraenoic acids (HETEs) induce degranulation of human neutrophils. J Immunol 1980; 124: 2100-2104
24 Stenson WF, Parker CW, Sullivan TJ. Augmentation of IgEmediated release of histamine by 5-hydroxyeicosatetraenoic acid and 12-hydroxyeicosatetraenoic acid. Biochem Biophys Res Commun 1980; 96: 1045-1052
25 Graeber JE, Walenga RW, Conner TB, Stuart MJ, Glaser BM. Hydroxyeicosatetraenoic acids (12- and 15-HETE) alter endothelial cell migration in vitro. Fed Proc 1984; 43: 588
26 Crutchley DJ. Hydroxyeicosatetraenoic acids and other unsaturated fatty acids inhibit endotoxin-induced thromboplastin activity in human monocytes. Biochem Biophys Res Commun 1985; 132: 67-53
27 Hajjar DP, Marcus AJ, Hajjar KA. Interactions of arterial cells. Studies on the mechanisms of endothelial cell modulation of chlores-terol metabolism in co-cultured smooth muscle cells. J Biol Chem 1987; 263: 6976-6981
28 Setty BN Y, Graeber JE, Stuart MJ. The mitogenic effect of 15- and 12-hydroxyeicosatetraenoic acid on endothelial cells may be mediated via diacylglycerol kinase inhibition. J Biol Chem 1987; 261: 17613-17622
29 Larrue J, Rigaud M, Razaka G, Daret D, Demond-Henri J, Bricaud H. Formation of monohydroxyeicosatetraenoic acids form arachidonic acid by cultured rabbit aortic smooth muscle cells. Biochem Biophys Res Commun 1983; 112: 242-249
30 Bailey JM, Bryant RW, Whiting J, Salata K. Characterization of 11-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid together with prostacyclin, as major product of the cyclooxygenase pathway in cultured rat aorta smooth muscle cells. J Lipid Res 1983; 24: 1419-1428
31 Takayama H, Gimbrone MA, Schafer AI. Vascular lipoxygenase activity:synthesis of 15-hydroxyeicosatetraenoic acid form arachidonic acid by blood vessels and cultured vascular endothelial cells. Thromb Res 1987; 45: 803-816
32 Feinmark SJ, Cannon PJ. Vascular smooth muscle cell leukotriene C₄synthesis: requirement for transcellular leukotriene A₄ metabolism. Biochim Biophys Acta 1987; 922: 125-135
33 Reinders JH, de Groot PHG, Gonzalves MD, Zandbergen J, Loesberg C, van Mourik JA. Isolation of a storage and secretory organelle containing von Willebrand protein from cultured human endothelial cells. Biochim Biophys Acta 1984; 804: 361-369
34 Powell WS. Reversed-Phase High-Pressure Liquid Chromatography ofarchidonic acid metabolites formed by cyclooxygenase andlipoxygenase. Anal Biochem 1985; 148: 56-69
35 Willems Ch, de Groot Ph, Pool GA, Gonzalves MS, van Aken WG, van Mourik JA. Arachidonate metabolism in cultured human vascular endothelial cells. Evidence for two prostaglandin synthetic pathways sensitive to acetylsalicylic acid. Biochim Biophys Acta 1982; 713: 581-588
36 Hopkins NK, Oglesby TD, Bundy GL, Gorman RR. Biosynthesis and metabolism of 15-hydroperoxy-5,8,ll,13-eicosatetraenoic acid by human umbilical vein endothelial cells. J Biol Chem 1984; 259: 14048-14053
37 Docherty JC, Wilson TW. Indomethacin increases the formation of lipoxygenase products in calcium-ionophore-stimulated human neutrophils. Biochem Biophys Res Commun 1987; 148: 534-538
38 Setty BN Y, Stuart MJ, Walenga RW. Formation of 11-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid in human umbilical arteries is catalyzed by cyclooxygenase. Biochim Biophys Acta 1985; 833: 484-494
39 Stenson WJ, Parker CW, Stuart MJ. 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid, a chemotactic fatty acid, is incorporated into neutrophil phospholipids and triglyceride. Prostaglandins 1979; 18: 285-292
40 Marcus AJ, Safier LB, Ullman HL. et al 12S.20-dihydroxyeicosate-traenoic acid: a new icosanoid synthesized by neutrophils from 12S-hydroxyicosatetraenoic acid produced by thrombin- or collagen-stimulated platelets. Proc Natl Acad Sci USA 1984; 81: 903-907
41 Pawlowski NA, Scott WA, Andreach M, Cohn ZA. Uptake and metabolism of monohydroxy-eicosatetraenoic acids by macrophages. J Exp 1982; 155: 1653-1664
42 Schafer AI, Takayama H, Farrell S, Gimbrone Jr MA. Incorporation of platelet and leukocyte lipoxygenase metabolites by cultured vascular cells. Blood 1986; 67: 373-378
43 Stenson WF, Parker CW. Metabolism of arachidonic acid in ionophore-stimulated neutrophils. J Clin Invest 1979; 64: 1457-1465
44 Bonser RW, Siegel MI, Chung SM, McConnell RT, Cuatrecasas P. Esterification of an endogenously synthesized lipoxygenase product into granulocyte cellular lipids. Biochemistry 1981; 20: 5297-5301
45 Stenson WF, Nickells MW, Atkinson JP. Esterification of monohydroxy fatty acids into the lipids of a macrophage cell line. Prostaglandins 1983; 26: 253-264
46 Richards CF, Johnson AR, Campbell WB. Specific incorporation of 5-hydroxy-6,8,ll,14-eicosatetraenoic acid into phosphatidylcholine in human endothelial cells. Biochim Biophys Acta 1986; 875: 569-581
47 Buchanan MR, Maas TA, Lagarde N, Guichardant M. 13-Hydroxyoctadecadienoic acid is the vessel wall chemorepellant factor, LOX. J Biol Chem 1985; 260: 16056-16059
48 Warden CH, Friedkin M. Regulation of phosphatidylcholine biosynthesis by mitogenic growth factors. Biochim Biophys Acta 1984; 792: 270-280
49 Habenicht AJ R, Glomset JA, Goerig M, Gronwald R, Grulich J, Loth U, Schettler G. Cellcycle-dependent changes in arachidonic acid and glycerol metabolism in Swiss 3T3 cells stimulated by platelet-derived growth factor. J Biol Chem 1985; 260: 1370-1373
50 Lindahl M, Bruhn R, Tagesson C. Lysophosphatidylcholine and the inflammatory action of neutrophils. Scand J Clin Lab Invest 1988; 48: 303-311
51 Hofmann SL, Prescott SM, Majerus PW. The effects of mepacrine and p. Bromophenacyl Bromide on arachidonic acid release in human platelets. Arch Biochem Biophys 1982; 215: 237-244