Research Article| Volume 95, ISSUE 2, P198-201, April 2001

The endothelium: vascular control of haemostasis


      Within many general functions the endothelium is equipped with a number of mechanisms that prevent thrombus formation in the circulatory system. It harbours factors that interrupt the coagulation cascade, such as antithrombin III, the protein C receptor thrombomodulin, and tissue factor pathway inhibitor. It prevents platelet activation by the production of nitric oxide and prostacyclin, exonucleotidases and surface heparan sulphates. Furthermore, it can trigger and control fibrinolysis by the synthesis and release of tissue-type plasminogen activator and its inhibitor PAI-1. The general properties of the endothelium are subject to adaptation by environmental factors, such as inflammatory mediators and shear forces. Interleukin-1 and tumour necrosis factor-α reduce the antithrombotic properties of the endothelium. Furthermore, local variation exists between different vascular beds and vessel types, such as in the endometrium. While the endothelium controls blood fluidity on its apical side, adaptation of the endothelium also prepares its involvement in tissue repair upon inflammation or damage. The fibrin matrix, which is formed after damage of the vascular system, not only acts as a sealing of the wound, but also facilitates the repair process by providing a scaffolding for cell invasion and angiogenesis.


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      1. Bush PC, Owen WG. Interactions of thrombin with endothelium. In: Nossel HL, Vogel HJ, editors, Pathophysiology of the endothelial cell. New York: Academic Press, 1982. pp. 97–101.

      2. van Hinsbergh VWM, editor. Vascular Control of Hemostasis, Advances in Vascular Biology, vol. 1. New York: Harwood Academic Publishers, 1996.

        • Cines D.B.
        • Pollak E.S.
        • Buck C.A.
        • Loscalzo J.
        • Zimmerman G.A.
        • McEver R.P.
        • Pober J.S.
        • Wick T.M.
        • Konkle B.A.
        • Schwartz B.S.
        • Barnathan E.S.
        • McCrae K.R.
        • Hug B.A.
        • Schmidt A.M.
        • Stern D.M.
        Endothelial cells in physiology and in the pathophysiology of vascular disorders.
        Blood. 1998; 91: 3527-3561
        • van Hinsbergh V.W.M.
        Endothelial permeability for macromolecules. Mechanistic aspects of pathophysiological modulation.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1018-1023
        • Mantovani A.
        • Bussolino F.
        • Introna M.
        Cytokine regulation of endothelial cell function: from molecular level to the bedside.
        Immunol. Today. 1997; 18: 231-240
        • Etzioni A.
        • Doerschuk C.M.
        • Harlan J.M.
        Of man and mouse: leukocyte and endothelial adhesion molecule deficiencies.
        Blood. 1999; 94: 3281-3288
        • Ross R.
        Atherosclerosis-an inflammatory disease.
        N. Engl. J. Med. 1999; 340: 115-126
        • Davie E.W.
        • Fujikawa K.
        • Kisiel W.
        The coagulation cascade: initiation, maintenance, and regulation.
        Biochemistry. 1991; 30: 10363-10370
        • Sixma J.J.
        • Wester J.
        The hemostatic plug.
        Semin. Haematol. 1977; 14: 165-199
      3. Rosenberg RD, Bauer KA. The heparan sulphate-antithrombin pathway: a natural anticoagulant mechanism of the blood vessel wall. In: van Hinsbergh VWM, editor. Vascular control of hemostasis. New York: Harwood Academic Publishers, 1996. pp. 39–71.

        • Esmon C.T.
        The roles of protein C and thrombomodulin in the regulation of blood coagulation.
        J. Biol. Chem. 1989; 264: 4743-4746
      4. Contribution of Bertina, 2000.

        • Rapaport S.I.
        • Rao L.V.
        The tissue factor pathway: how it has become a prima ballerina.
        Thromb. Haemost. 1995; 74: 7-17
        • Sixma J.J.
        • van Zanten G.H.
        • Huizinga E.G.
        • van der Plas R.M.
        • Verkley M.
        • Wu Y.P.
        • Gros P.
        • de Groot P.G.
        Platelet adhesion to collagen: an update.
        Thromb. Haemost. 1997; 78: 434-438
        • Gerritsen M.E.
        Functional heterogeneity of vascular endothelial cells.
        Biochem. Pharmacol. 1987; 36: 2701-2711
        • Moncada S.
        Nitric oxide: discovery and impact on clinical medicine.
        J. R. Soc. Med. 1999; 92: 164-169
        • Busse R.
        • Fleming I.
        Pulsatile stretch and shear stress: physical stimuli determining the production of endothelium-derived relaxing factors.
        J. Vasc. Res. 1998; 35: 73-84
        • Pearson J.D.
        Endothelial cell function and thrombosis.
        Baillieres Best Pract. Res. Clin. Haematol. 1999; 12: 329-341
        • Collen D.
        The plasminogen (fibrinolytic) system.
        Thromb. Haemost. 1999; 82: 259-270
        • Kohler H.P.
        • Grant P.J.
        Plasminogen-activator inhibitor type 1 and coronary artery disease.
        N. Engl. J. Med. 2000; 342: 1792-1801
        • Emeis J.J.
        • van den Eijnden-Schrauwen Y.
        • van den Hoogen C.M.
        • de Priester W.
        • Westmuckett A.
        • Lupu F.
        An endothelial storage granule for tissue-type plasminogen activator.
        J. Cell. Biol. 1997; 139: 245-256
        • Wagner D.D.
        The Weibel–Palade body: the storage granule for von Willebrand factor and P-selectin.
        Thromb. Haemost. 1993; 70: 105-110
        • Ruggeri Z.M.
        Mechanisms initiating platelet thrombus formation.
        Thromb. Haemost. 1997; 78: 611-616
        • Topper J.N.
        • Gimbrone Jr, M.A.
        Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype.
        Mol. Med. Today. 1999; 5: 40-46
        • Lockwood C.J.
        • Krikun G.
        • Aigner S.
        • Schatz F.
        Effects of thrombin on steroid-modulated cultured endometrial stromal cell fibrinolytic potential.
        J. Clin. Endocrinol. Metab. 1996; 81: 107-112
        • Cameron I.T.
        • Campbell S.
        Nitric oxide in the endometrium. Review.
        Hum. Reprod. Update. 1998; 4: 565-569
        • Lockwood C.J.
        • Schatz F.
        A biological model for the regulation of peri-implantational hemostasis and menstruation. Review.
        J. Soc. Gynecol. Invest. 1996; 3: 159-165
        • Casslen B.
        • Urano S.
        • Lecander I.
        • Ny T.
        Plasminogen activators in the human endometrium, cellular origin and hormonal regulation.
        Blood Coagul. Fibrinolysis. 1992; 3: 133-138
        • Sandberg T.
        • Casslen B.
        • Gustavsson B.
        • Benraad T.J.
        Human endothelial cell migration is stimulated by urokinase plasminogen activator:plasminogen activator inhibitor 1 complex released from endometrial stromal cells stimulated with transforming growth factor beta1 possible mechanism for paracrine stimulation of endometrial angiogenesis.
        Biol. Reprod. 1998; 59: 759-767
        • Schatz F.
        • Soderland C.
        • Hendricks-Munoz K.D.
        • Gerrets R.P.
        • Lockwood C.J.
        Human endometrial endothelial cells: isolation, characterization, and inflammatory-mediated expression of tissue factor and type 1 plasminogen activator inhibitor.
        Biol. Reprod. 2000; 62: 691-697
        • Iruela-Arispe M.L.
        • Rodriguez-Manzaneque J.C.
        • Abu-Jawdeh G.
        Endometrial endothelial cells express estrogen and progesterone receptors and exhibit a tissue specific response to angiogenic growth factors.
        Microcirculation. 1999; 6: 127-140
      5. Colvin RB. Wound healing processes in hemostasis and thrombosis. In: Gimbrone MA, editor. Vascular endothelium in hemostasis and thrombosis. Edinburgh: Churchill Livingstone, 1986. pp. 220–41.

        • Dvorak H.F.
        Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing.
        N. Engl. J. Med. 1986; 315: 1650-1659
        • van Hinsbergh V.W.
        • Koolwijk P.
        • Hanemaaijer R.
        Role of fibrin and plasminogen activators in repair-associated angiogenesis: in vitro studies with human endothelial cells.
        EXS. 1997; 79: 391-411
        • Rogers P.A.W.
        • Gargett C.E.
        Endometrial angiogenesis.
        Angiogenesis. 1999; 2: 287-294