Thromb Haemost 1988; 59(02): 248-250
DOI: 10.1055/s-0038-1642763
Original Articles
Schattauer GmbH Stuttgart

Epidermal Growth Factor Stimulates Prostacyclin Production by Cultured Human Vascular Endothelial Cells

Ari Ristimäki
1   Children's Hospital, University of Helsinki, Helsinki, Finland
,
Olavi Ylikorkala
2   The Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland
,
Jaakko Perheentupa
1   Children's Hospital, University of Helsinki, Helsinki, Finland
,
Lasse Viinikka
1   Children's Hospital, University of Helsinki, Helsinki, Finland
› Author Affiliations
Further Information

Publication History

Received 04 August 1987

Accepted after revision 03 December 1987

Publication Date:
21 May 2018 (online)

Summary

Epidermal growth factor (EGF) stimulated prostacyclin (PGI2) production by cultured human umbilical vein endothelial cells, as measured by radioimmunoassay of its stable metabolite 6-keto- prostaglandin F. This effect of EGF was dose-dependent, the lowest stimulatory concentration of EGF was 1.0 ng/ml and 100 ng/ml caused a 2.7 ± 0.3 (mean ± SEM) fold increase in the PGI2 synthesis. The stimulation appeared at 3-6 h of incubation and lasted at least 24 h. It was suppressed by EGF antibodies and blocked by protein synthesis inhibitor cycloheximide. Cells preincubated 12 h with EGF released also higher amounts of PGI2when incubated with thrombin for 5 min. It is concluded that EGF liberated from platelets during aggregation may prevent local thrombogenesis and atherogenesis by stimulating the release of the antiaggregatory, vasodilatory PGI2 from vascular endothelial cells.

 
  • References

  • 1 Moncada S, Vane JR. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin. Pharmacol Rev 1979; 30: 293-331
  • 2 Ross R. The pathogenesis of atherosclerosis - an update. N Engl J Med 1986; 314: 488-500
  • 3 Coughlin SR, Moskowitz MA, Zetter BR, Antoniades HN, Levine L. Platelet-dependent stimulation of prostacyclin synthesis by platelet-derived growth factor. Nature 1980; 288: 600-602
  • 4 Seid JM, Jones PB B, Russel RG G. The presence in normal plasma, serum and platelets of factors that stimulate the production of prostcycylin (PGT) by cultured endothelial cells. Clin Sci 1983; 64: 387-394
  • 5 Tremoli E, Jaffe EA, Goldman KT, Weksler BB. Prostacyclin production by endothelial cells. Effects of sera from normal and hyperlipidemic subjects. Arteriosclerosis 1985; 5: 178-185
  • 6 Levine L, Hassid A. Epidermal growth factor stimulates prostaglandin biosynthesis by canine kidney (MDCK) cells. Biochem Biophys Res Commun 1977; 76: 1181-1187
  • 7 Rigas A, Levine L. Arachidonic acid metabolism by rat liver cells (the C-9 cell line). J Pharmacol Exp Ther 1984; 231: 230-235
  • 8 Hirata Y, Uchihashi M, Nakashima H, Fujita T, Matsukura S. Stimulatory effect of epidermal growth factor on prostaglandin E2 production in mouse fibrosarcoma cell line (HSDM! Q).. Horm metabol Res 1985; 17: 448-450
  • 9 Takasu N, Sato S, Yamada T, Shimizu Y. Epidermal growth factor (EGF) and tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulate pg synthesis and thymidine incorporation in cultured porcine thyroid cells. Biochem Biophys Res Commun 1987; 143: 880-884
  • 10 Gospodarowicz D, Brown KD, Birdwell CR, Zetter BR. Control of proliferation of human vascular endothelial cells. Characterization of the response of human umbilical vein endothelial cells to fibroblast growth factor, epidermal growth factor, and thrombin. J Cell Biol 1978; 77: 774-788
  • 11 Oka Y, Orth DN. Human plasma epidermal growth factor/(3-urogastrone is associated with blood platelets. J Clin Invest 1983; 72: 249-259
  • 12 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria J Clin Invest 1973; 52: 2745-2756
  • 13 Johnson RA, Morton DR, Kinner JH, Gorman RR, McGuire JC, Sun FF, Whittaker N, Bunting S, Salmon J, Moncada S, Vane JR. The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 1976; 12: 915-928
  • 14 Mäkilä U-M, Jouppila P, Kirkinen P, Viinikka L, Ylikorkala O. Relation between umbilical prostacyclin production and blood-flow in the fetus. Lancet 1983; 1: 728-729
  • 15 Sorger T, Germinario RJ. A direct solubilization procedure for the determination of DNA and protein in cultured fibroblasts monolayers. Anal Biochem 1983; 131: 254-256
  • 16 Carpenter G, Cohen S. Epidermal growth factor. Ann Rev Biochem 1979; 48: 193-216
  • 17 Haudenschild C, Zahniser D, Folkman J, Klagsbrun M. Human vascular endothelial cells in culture. Lack of response to serum growth factors Exptl Cell Res 1976; 98: 175-183
  • 18 Assoian RK, Grotendorst GR, Miller DM, Sporn MB. Cellular transformation by coordinated action of three peptide growth factors from human platelets. Nature 1984; 309: 804-806
  • 19 Callahan KS, Schorer A, Harlan JM. Platelet-derived growth factor does not stimulate prostacyclin synthesis by cultured endothelial cells. Blood 1986; 67: 131-134
  • 20 Weksler BB, Ley CW, Jaffe EA. Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and ionophore A 23187. J Clin Invest 1978; 62: 923-930
  • 21 Nawroth PP, Stern DM, Kaplan KL, Nossel HL. Prostacyclin production by perturbed bovine aortic endothelial cells in culture. Blood 1984; 64: 801-806
  • 22 Rossi V, Breviario F, Ghezzi P, Dejana E, Mantovani A. Prostacyclin synthesis induced in vascular cells by interleukin-1. Science 1985; 229: 174-176
  • 23 Kawakami M, Ishibashi S, Ogawa H, Murase T, Takaku F, Shibata S. Cachectin/ TNF as well as interleukin-1 induces prostacyclin synthesis in cultured vascular endothelial cells. Biochem Biophys Res Commun 1986; 141: 482-487
  • 24 Mantovani A, Dejana E. Modulation of endothelial function by interleukin-1. A novel target for pharmacological intervention?. Biochem Pharmacol 1987; 36: 301-305
  • 25 Sinzinger H, Zidek T, Fitscha P, Wagner O, Rogatti W. PGI2 and PGEX inhibit smooth muscle cell proliferation, mitotic activity and extracellular matrix formation. Thromb Haemostas 1987; 58: 272 (Abstr 999)