Endothelial Cell Function in Hemostasis and Thrombosis

  • Kenneth Kun-yu Wu
  • Karen Frasier-Scott
  • Helen Hatzakis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 242)


The endothelium comprises a single layer of polygonal cells lining the entire length of blood vessels. It plays a pivotal role in modulating a number of physiologic and pathophysiologic processes including hemostasis, thrombosis, inflammation and immune responses.1 This review will focus on the endothelial cell function in hemostasis and thrombosis. Hemostasis is a complex event involving multiple interactions between blood cells and the damaged vessel wall, the coagulation proteins and blood cell constituents and the cell-cell interactions. These complex biologic processes generally do not occur without endothelial damage. Intact endothelium appears to function not only as a physical barrier which blocks active interaction between the cellular and protein constituents of blood and the vessel wall but also as a biologically active tissue capable of synthesizing compounds that promote and control hemostatic function. Moreover, its surface possesses specific properties for modulating certain key reactions in the coagulation cascade.


Endothelial Cell Plasminogen Activator Tissue Factor Platelet Adhesion Fibrinolytic Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    M.A. Gimbrone, ed., “Vascular endothelium in Hemostasis and Thrombosis,” Churchill Livingstone, Edinburgh (1986).Google Scholar
  2. 2.
    C.T. Esmon and W.G. Owen, Identification of an endothelial cell cofactor for thrombin catalyzed activation of protein, C. Proc, Natl. Acad. Sci (USA) 78:2249–2252 (1981).CrossRefGoogle Scholar
  3. 3.
    W.G. Owen and C.T. Esmon, Functional properties of an endothelial cell cofactor for thrombincatalyz-ed activation of protein, C. J. Biol. Chem. 256:5532–5535 (1981).Google Scholar
  4. 4.
    F.J. Walker, P.W. Sexton and C.T. Esmon, The inhibition of blood coagulation by activated protein C through the selective inactivation of activated factor V, Biochim. Biophys. Acta 571:333–342 (1979).PubMedCrossRefGoogle Scholar
  5. 5.
    F.J. Walker, Regulation of activated protein C by protein S: The role of phospholipid in factor Va inactivation, J. Biol. Chem. 256:11128–11131 (1981).PubMedGoogle Scholar
  6. 6.
    P.C. Comp and C.T. Esmon, Generation of fibrinolytic activity by infusion of activated protein C into dogs, J. Clin. Invest. 68:1221–1228 (1981).PubMedCrossRefGoogle Scholar
  7. 7.
    N. Savion, J.D. Issacs, D. Gospaclarowicz and M.A. Shuman, Internalization and degradation of thrombin and up regulation of thrombin binding sites in corneal endothelial cells, J. Biol. Chem. 256:4514–4519 (1981).PubMedGoogle Scholar
  8. 8.
    J.A. Marcimi and R.D. Rosenberg, Anticoagulantly active heparin-like molecules from vascular tissue, Biochem. 23:1730–1737 (1984).CrossRefGoogle Scholar
  9. 9.
    J.A. Marcum, L. Fritze, S.J. Galli, G. Karp and R.D. Rosenberg: Microvascular heparin-like species with anticoagulant activity, Amer. J. Physiol. 245:H725–733 (1983).PubMedGoogle Scholar
  10. 10.
    Y. Nemerson and R. Bach: Tissue factor revisited, Progress in Hemost. and Thromb. 6:237–261 (1982).Google Scholar
  11. 11.
    M.P. Bevilacqua, J.S. Pober, G.R. Majeau, R.S. Cotran and M.A. Gimbrone, Jr. Interleukin-1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells, J. Exp. Med. 160:618–623 (1984).PubMedCrossRefGoogle Scholar
  12. 12.
    D.M. Stern, M. Drillings, H.L. Nossel, A. Hurlet-Jensen, K. La Gamma and J. Owen, Binding of factor IX and IXa to cultured vascular endothelial cells, Proc. Natl. Acad. Sci. (USA) 80:4119–4123 (1983).PubMedCrossRefGoogle Scholar
  13. 13.
    P.P. Nawroth and D.M. Stern, An endothelial cell coagulant pathway,J. Cellular Biochem 28:253–264 (1985).CrossRefGoogle Scholar
  14. 14.
    D.M. Stern, P.P. Nawroth, W. Kisil, G. Vehar and C.T. Esmon, The binding of factor IXa to cultured bovine aortic endothelial cells, J. Biol. Chem. 260:6717–6722 (1985).PubMedGoogle Scholar
  15. 15.
    T.S. Zimmerman, Z.M. Ruggeri and C.A. Fulcer, Factor VIII/VWF factor. In “Progress in Hematology,” E.B. Brown, ed., Grune and Stratton, New York. Vol. 13, P. 279–309 (1983).Google Scholar
  16. 16.
    D.C. Lynch, R. Williams, T.S. Zimmerman, E.P. Kirby and D.M. Livingston, Biosynthesis of the subunit of factor VIIIR by bovine aortic endothelial cells, Proc. Natl. Acad. Sci. (USA) 180: 2738–2742 (1983).CrossRefGoogle Scholar
  17. 17.
    D.D. Wagner and V.G. Marder, Biosynthesis of vWF protein by human endothelial cells, J. Biol. Chem. 258:2065–2067 (1983).PubMedGoogle Scholar
  18. 18.
    D.D. Wagner, J.B. Olmstead and V.J. Marder, Immunolocalization of vWF in Weibel-Palade bodies of human endothelial cells, Cell Biol. 95:355–360 (1982).CrossRefGoogle Scholar
  19. 19.
    B.M. Ewenstein, M.J. Warhol, R.I. Handln and J.S. Pober, Composition of the vWF storage organelle (Weibel-Palde body) isolated from cultured human umbilical vein endothelial cells, J. Cell Biol. 104:1423–1433 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    J.J. Sixma, K.S. Sakariassen and P.A. Bohuis, The relationship between the multimeric structure of factor VIII/vWF and the facilitation of platelet adhesion to human subendothelium, Thromb. andHaemost. 46:199 (1981).Google Scholar
  21. 21.
    L.W. Hoyer, The factor VIII complex: Structure cell function, Blood 58:1–13 (1981).PubMedGoogle Scholar
  22. 22.
    D.F. Mosher, M.J. Doyle and E.A. Jaffe, Synthesis and secretion of thrombospondin by cultured human endothelial cells, J. Cell Biol. 93:343–348 (1982).PubMedCrossRefGoogle Scholar
  23. 23.
    H. Sage, Characterization and modulation of extracellular glycoproteins secreted by endothelial cells in culture in vascular endothelium, in “Hemostasis and Thrombosis.” M.A. Gimbrone Jr., ed. Livingstone, Edinburgh, pp. 187–208 (1986).Google Scholar
  24. 24.
    D. Collen, On the regulation and control of fibrinolysis,Thromb. and Haemost. 43:77–89 (1980).Google Scholar
  25. 25.
    D.J. Loskutoff and T.S. Edgington, Synthesis of a fibrinolytic activator and inhibitor by endothelial cells, Proc. Natl. Acad. Sci. (USA) 74:3903–3907 (1977).CrossRefGoogle Scholar
  26. 26.
    D.J. Loskutoff, J.A. VanMourik, L.A. Erickson and D. Lawrence, Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells, Proc. Natl. Acad. Sci. (USA) 80:2956–2960 (1983).CrossRefGoogle Scholar
  27. 27.
    S. Moncada, R. Gryglewski, S. Bunting and J.R. Vane, An enzyme isolated from arteries transform prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation, Nature 263:663–665 (1974).CrossRefGoogle Scholar
  28. 28.
    B.B. Weksler, Prostacyclin. In “Progress in Hemostasis and Thrombosis,” T.H. Spaet ed., Grune and Staton, New York. Vol. 6 113–138 (1982).Google Scholar
  29. 29.
    B.B. Weksler, C.W. Ley and E.A. Jaffe, Stimulation of endothelial cell prostacyclin production by thrombin, trypsin and ionophore A23187, Clin. Invest. 62:923–930 (1978).CrossRefGoogle Scholar
  30. 30.
    N.L. Baenziger, L.E. Force and P.R. Becherer, Histamine stimulates PGI2 synthesis in cultured human umbilical vein endothelial cells, Biochem. Biophys. Res. Comm. 92:1435–1440 (1980).PubMedCrossRefGoogle Scholar
  31. 31.
    J.C. Goldsmith and J.J. McCormick, Immunologic injury to vascular endothelial cells: Effects on release of prostacyclin. Blood 63:984–989 (1984).PubMedGoogle Scholar
  32. 32.
    F. Alhence-Gelas, S.J. Tsai, K.S. Callahan, W.B. Campbell and A.R. Johnson, Stimulation of prostaglandin formation by vasoactive cells, Prostagl. 24:723–742 (1982).CrossRefGoogle Scholar
  33. 33.
    D.K. Miller, S. Sadowski, D.D. Soderman and F.A. Kuehl, Endothelial prostacyclin production induced by activated neutrophils, J. Biol. Chem. 260:1006–1014 (1985).PubMedGoogle Scholar
  34. 34.
    D.J. Loskutoff, Effect of thrombin on the fibrinolytic activity of cultured bovine endothelial cells, J. Clin, Invest. 64:329–332 (1979).CrossRefGoogle Scholar
  35. 35.
    M.P. Bevilacqua, J.S. Pober, M.E. Wheeler, R.S. Cotran and M.A. Gimbrone Jr., IL-1 activation of vascular endothelium: effects on procoagulant activity and leukocyte adhesion, Am. J. Pathol. 121:394–403 (1985).PubMedGoogle Scholar
  36. 36.
    M.P. Bevilacque, R.R. Schleef, M A Jr. Gimbrone and D.J. Loskutoff, Regulation of fibrinolyticsystem of cultured human vascular endothelium by IL-1, Clin. Invest 78:587–591 (1986).CrossRefGoogle Scholar
  37. 37.
    D.A. Morgan, F.W. Ruscelli and R.C. Gallo, Selective in vitro growth of lymphocytes from normal human bone marrows, Science 193:1007–1008 (1976).PubMedCrossRefGoogle Scholar
  38. 38.
    F.W. Ruscetti, D.A. Morgan and R.C. Gallo, Functional and morphologic characterization of human T cell continuously growth in vitro,J. Immunol. 119:131–138 (1977).PubMedGoogle Scholar
  39. 39.
    J.M. Zarling and F.H. Bach, Continuous culture of T cells cytotoxic for autologous human leukemiacells, Nature 280:685–688 (1979).PubMedCrossRefGoogle Scholar
  40. 40.
    S. Gillis, K.A. Smith and J. Watson, Biochemical and biologic characterization of lymphocyte regulatory molecules. II. Purification of a class of rat and human lymphokines, J. Immunol. 124:1954–1962 (1980).PubMedGoogle Scholar
  41. 41.
    C.S. Henney, K. Kuribayashi, D.E. Kern and S. Gillis, Interleukin-2 augments natural killer cell activity, Nature 291: 335–338 (1981).PubMedCrossRefGoogle Scholar
  42. 42.
    J.R. Ortaldo, A.T. Mason, J.P. Gerard, L.E. Henderson, W. Farrar, R.F. Hopkins, R.B. Herber-man and H. Rabin, Effect of natural and recombinant IL-2 on regulation of IFN-y production and natural killer cell activity, J. Immunol. 133:779–783 (1984).PubMedGoogle Scholar
  43. 43.
    M.C. Mingari, F. Gerora, G. Carra, R.S. Acold, A. Moretta, R.H. Zubler, T.A. Waldman and L. Moretta, Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells, Nature 312:641–643 (1984).PubMedCrossRefGoogle Scholar
  44. 44.
    B.C. Pike, A. Raubitischets and G.J.V. Nossal, Human interleukin 2 can promote the growth and differentiation of single hapten-specific B cells in the presence of specific antigen, Proc. Natl. Acad. Sci. 81:7917–7921 (1984).PubMedCrossRefGoogle Scholar
  45. 45.
    E.A. Grimm, A. Mazumder, H. Zhang and S.A. Rosenber, Lymphokine-activated killer cell phenomenon: Lysis of natural killer resistant fresh solid tumor cells by interleukin 2 activated autologous human peripheral blood lymphocytes, J. Exp. Med. 155:1823–1841 (1982).PubMedCrossRefGoogle Scholar
  46. 46.
    A. Mazumder and S.A. Rosenberg, Successful immunotherapy of natural killer resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of synegeneic lymphocytes activated in vitro by interleukin 2, J. Exp. Med. 159:495–507 (1984).PubMedCrossRefGoogle Scholar
  47. 47.
    E.R. Hall, A.C. Papp, W.E. Jr. Scifert and K.K. Wu, Stimulation of endothelial cell prostacyclin formation by IL-2,Lymphokine Res. 5:87–96 (1986).PubMedGoogle Scholar
  48. 48.
    E.A. Hann, R.A. Egan, D.D. Soderman, P.H. Gale and F.A. Kuehl, Jr., Peroxidase-dependent deactivation of prostacyclin synthetase, J. Biol. Chem. 254:2191–2194 (1979).Google Scholar
  49. 49.
    R.W. Egan, J. Paxton and F.A. Keuhl, Jr., Mechanism for irreversible self-deactivation of prostaglandin synthetase, J. Biol. Chem. 251:7325–7335 (1976).Google Scholar
  50. 50.
    M.E. Hemler and W.E.M. Lands, Evidence for a peroxide-initiated free radical mechanism of prostaglandin biosynthesis, J. Biol. Chem. 255:6253–6261 (1980).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Kenneth Kun-yu Wu
    • 1
  • Karen Frasier-Scott
    • 1
  • Helen Hatzakis
    • 1
  1. 1.Division of Hematology-Oncology Department of Internal MedicineUniversity of Texas, Health Science Center at HoustonHoustonUSA

Personalised recommendations