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Thromb Haemost 1994; 72(05): 770-776
DOI: 10.1055/s-0038-1648956
Original Article
Schattauer GmbH Stuttgart

Heparin Enhances Endothelial Cell von Willebrand Factor Content by Growth Factor Dependent Mechanisms

Susan H Tannenbaum
The Hematology Service, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
,
Elizabeth S Chao
The Hematology Service, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
,
Harvey R Gralnick
The Hematology Service, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
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Publikationsverlauf

Received 17. März 1994

Accepted after resubmission 01. August 1994

Publikationsdatum:
06. Juli 2018 (online)

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Summary

Von Willebrand factor (vWf), a multimeric adhesive glycoprotein synthesized, stored, and secreted in megakaryocytes and endothelial cells, is normally found in plasma, platelets and subendothelium. While many substances mediate the release of vWf from endothelial cells, factors that enhance vWf synthesis and partitioning to its regulated pathway are currently unknown. We studied the effect of pharmacologic doses of heparin on the vWf content of endothelial cells. After a lag of 8 h and in the presence of crude or purified growth factor, heparin at doses between 0.25 and 2 U (1.4-11 μg)/ml, increased the content of high moleculr weight vWf. The increased amounts of vWf were localized to Weibel-Palade bodies and extracellular matrix. Lower molecular weight highly sulfated heparin or heparin-like compounds were most active in growth factor dependent endothelial cell vWf expression. There was no clear importance of polysaccharide sequence or protein core.

 

  • References

  • 1 Wagner DD. Cell biology of von Willebrand factor. Annu Rev Cell Biol 1990; 6: 217-216
    CrossrefPubMedGoogle Scholar
  • 2 Ruggeri ZM, Zimmerman TS. Von Willebrand factor and von Willebrand disease. Blood 1987; 70: 895-904
    PubMedGoogle Scholar
  • 3 Nishino M, Girma JP, Rothschild C, Fressinaud E, Meyer D. New variant of von Willebrand disease with defective binding to factor VIII. Blood 1989; 74: 1591-1599
    PubMedGoogle Scholar
  • 4 Mazurier C, Dieval J, Jorieux S, Delobel J, Goudemand M. A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWf. Characterization of abnormal vWF/FVIII interaction. Blood 1990; 75: 20-26
    PubMedGoogle Scholar
  • 5 Wagner DD, Marder VJ. Biosynthesis of von Willebrand protein by human endothelial cells. J Biol Chem 1983; 258: 2065-2067
    PubMedGoogle Scholar
  • 6 Lynch DC, Williams R, Zimmerman TS, Kirby EP, Livingston DM. Biosynthesis of the subunits of factor VIIIR by bovine aortic endothelial cells. Proc Nat Acad Sci USA 1983; 80: 2738-2712
    CrossrefPubMedGoogle Scholar
  • 7 Wagner DD, Marder VJ. Biosynthesis of von Willebrand protein by human . endothelial cells: processing steps and their intracellular localization. J Cell Biol 1984; 99: 2123-2130
    CrossrefPubMedGoogle Scholar
  • 8 Wagner DD, Fay PJ, Sporn LA, Lawrence SO, Sinha S, Marder VJ. Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells. Proc Nat Acad Sci USA 1987; 84: 1955-1959
    CrossrefPubMedGoogle Scholar
  • 9 Wagner DD, Olmsted JB, Marder VJ. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol 1982; 95: 355-360
    CrossrefPubMedGoogle Scholar
  • 10 Ewenstein BM, Warhol MJ, Handin RI, Pober JS. Composition of the von Willebrand factor storage organelle (Weibel-Palade body) isolated from cultured human umbilical vein endothelial cells. J Cell Biol 1987; 104: 1423-1433
    CrossrefPubMedGoogle Scholar
  • 11 Loesberg C, Gonsalves MD, Zandbergen J, Willems C, Aken WGv, Stel HV, Mourik JAv, Groot PGd. The effect of calcium on the secretion of factor VIII-related antigen by cultured human endothelial cells. Biochim Biophys Acta 1983; 763: 160-168
    CrossrefPubMedGoogle Scholar
  • 12 Sporn LA, Marder VJ, Wagner DD. Inducible secretion of large biologically potent von Willebrand factor multimers. Cells 1986; 46: 185-190
    CrossrefPubMedGoogle Scholar
  • 13 Reinders JH, de Groot PG, Sixma JJ, van Mourik JA. Storage and secretion of von Willebrand factor by endothelial cells. Haemostasis 1988; 18: 246-261
    PubMedGoogle Scholar
  • 14 Ingber DE, Folkman J. Mechanochemical switching, between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix. J Cell Biol 1989; 109: 317-330
    CrossrefPubMedGoogle Scholar
  • 15 Maciag T, Kadish J, Wilkins L, Stemerman MB, Weinstein R. Organizational behavior of human umbilical vein endothelial cells. J Cell Biol 1982; 94: 511-520
    CrossrefPubMedGoogle Scholar
  • 16 Kubota Y, Kleinman HK, Martin GR, Lawley TJ. Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures. J Cell Biol 1988; 107: 1589-1598
    CrossrefPubMedGoogle Scholar
  • 17 Tannenbaum SH, Chao ES, Gralnick HR. Von Willebrand Factor in Differentiated Endothelial Cells. Blood 1991; 78: 149
    PubMedGoogle Scholar
  • 18 Friesei R, Komoriya A, Maciag T. Inhibition of endothelial cell proliferation by gamma-interferon. J Cell Biol 1987; 104: 689-696
    CrossrefPubMedGoogle Scholar
  • 19 Tannenbaum SH, Gralnick HR. γ-Interferon modulates von Willebrand factor release by cultured human endothelial cells. Blood 1990; 75: 2177-2184
    PubMedGoogle Scholar
  • 20 Maciag T, Hoover GA, Stemerman MB, Weinstein R. Serial propagation of human endothelial cells in vitro. J Cell Biol 1981; 91: 420-426
    CrossrefPubMedGoogle Scholar
  • 21 Johnson TE, Umbemhauer PR, Hill R, Bradt C, Mueller SN, Levine EM, Nichols WW. Karyotypic and phenotypic changes during in vitro aging of human endothelial cells. J Cell Physiol 1992; 150: 17-27
    CrossrefPubMedGoogle Scholar
  • 22 Dichek D, Quertermous T. Variability in messenger RNA levels in human umbilical vein endothelial cells of different lineage and time in culture. IN VITRO Cell Dev Biol 1989; 25: 289-292
    CrossrefPubMedGoogle Scholar
  • 23 Maciag T, Cerundolo J, Ilsley S, Kelley PR, Forand R. An endothelial cell growth factor from bovine hypothalamus: Identification and partial characterization. Proc Nat Acad Sci USA 1979; 76: 5674-5678
    CrossrefPubMedGoogle Scholar
  • 24 Thornton SC, Mueller SN, Levine EM. Human endothelial cells: use of heparin in cloning and long-term serial cultivation. Science 1983; 222: 623-625
    CrossrefPubMedGoogle Scholar
  • 25 Maciag T, Mehlman T, Friesei R. Heparin binds endothelial cell growth factor, the principal endothelial cell mitogen in bovine brain. Science 1984; 225: 932-935
    CrossrefPubMedGoogle Scholar
  • 26 Schreiber AB, Kenny J, Kowalski J, Friesei R, Mehlman T, Maciag T. The interaction of endothelial cell growth factor with heparin: characterization by receptor and antibody recognition. Proc Nat Acad Sci USA 1985; 82: 6138-6143
    CrossrefPubMedGoogle Scholar
  • 27 Jaffe EA, Hoyer LW, Nachman RL. Synthesis of antihemophilic factor antigen by cultured endothelial cells. J Clin Invest 1973; 52: 2757-2764
    CrossrefPubMedGoogle Scholar
  • 28 Gimbrone MA, Cotran RS, Folkman J. Human vascular endothelial cells in culture: Growth and DNA synthesis. J Cell Biol 1974; 60: 673-684
    CrossrefPubMedGoogle Scholar
  • 29 Home MK, Chao ES. The effect of molecular weight on heparin binding to platelets. Br J Haematol 1990; 74: 306-312
    CrossrefPubMedGoogle Scholar
  • 30 Tannenbaum SH, Rick ME, Shafer B, Gralnick HR. Subendothelial matrix of cultured endothelial cells contains fully processed high molecular weight von Willebrand factor. J Lab Clin Med 1989; 113: 372-378
    PubMedGoogle Scholar
  • 31 Gralnick HR, Williams S, McKeown LP, Maisonneuve P, Jenneau C, Sultan Y, Rick ME. In vitro correction of the abnormal multimeric structure of von Willebrand factor in type Ha von Willebrand’s disease. Proc Nat Acad Sci USA 1985; 82: 5968-5972
    CrossrefPubMedGoogle Scholar
  • 32 Hoyer LW. Immunologic studies of antihemophilic factor (AHF, factor VIII). IV. Radioimmunoassay for AHF antigen. J Lab Clin Med 1972; 80: 822-833
    PubMedGoogle Scholar
  • 33 Bonfanti R, Furie BC, Furie B, Wagner DD. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood 1989; 73: 1109-1112
    PubMedGoogle Scholar
  • 34 Gralnick HR, Williams S, McKeown LP, Connaghan C, Shafer B, Hansmann K, Magruder L, Vail M. Platelet activation and alpha granule secretion in type IIB von Willebrand’s disease. Br J Haematol 1991; 79: 618-623
    CrossrefPubMedGoogle Scholar
  • 35 Tannenbaum SH, Finko R, Cines DB. Antibody and immune complexes induce tissue factor production by human endothelial cells. J Immunol 1986; 137: 1532-1537
    PubMedGoogle Scholar
  • 36 Sporn LA, Chavin SI, Marder VJ, Wagner DD. Biosynthesis of von Willebrand protein by human megakaryocytes. J Clin Invest 1985; 76: 1102-1106
    CrossrefPubMedGoogle Scholar
  • 37 Reinders JH, de Groot PG, Dawes J, Hunter NR, van Heusten HA, Zandbergen J, Gonsalves MD, van Mourik JA. Comparison of secretion and subcellular localization of von Willebrand protein with that of throm-bospondin and fibronectin in cultured human vascular endothelial cells. Biochim Biophys Acta 1985; 844: 306-313
    CrossrefPubMedGoogle Scholar
  • 38 Burgess TL, Kelly RB. Constitutive and regulated secretion of proteins. Annu Rev Cell Biol 1987; 3: 243-293
    CrossrefPubMedGoogle Scholar
  • 39 Wagner DD, Saffaripour S, Bonfanti R, Sadler JE, Cramer EM, Chapman B, Mayadas T. Induction of specific storage organelles by von Willebrand factor propolypeptide. Cell 1991; 64: 403-413
    CrossrefPubMedGoogle Scholar
  • 40 Mayadas T, Wagner DD, Simpson PJ. von Willebrand factor biosynthesis and partitioning between constitutive and regulated pathways of secretion after thrombin stimulation. Blood 1989; 73: 706-711
    CrossrefPubMedGoogle Scholar
  • 41 Konkle BA, Ginsburg D. The addition of endothelial cell growth factor and heparin to human umbilical vein endothelial cell cultures decreases plasminogen activator inhibitor-I expression. J Clin Invest 1988; 82: 579-585
    CrossrefPubMedGoogle Scholar
  • 42 Almus FE, Rao LVM, Rapaport SI. Decreased inducibility of tissue factor activity on human umbilical vein endothelial cells cultured with endothelial cell growth factor and heparin. Thromb Res 1988; 50: 339-344
    CrossrefPubMedGoogle Scholar
  • 43 Minter AJ, Dawes J, Chesterman CN. Effects of heparin and endothelial cell growth supplement on haemostatic function of vascular endothelium. Thromb Haemost 1992; 67: 718-723
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 44 Gospodarowicz D, Cheng J. Heparin protects basic and acidic FGF from inactivation. J Cell Physiol 1986; 128: 475-484
    CrossrefPubMedGoogle Scholar
  • 45 Presta M, Rifkin DB. New aspects of blood vessel growth: tumor and tissue-derived angiogenesis factors. Haemostasis 1988; 18: 06-17
    PubMedGoogle Scholar
  • 46 Nader HB, Buonassisi V, Colburn P, Dietrich CP. Heparin stimulates the synthesis and modifies the sulfation pattern of heparan sulfate proteoglycan from endothelial cells. J Cell Physiol 1989; 140: 305-310
    CrossrefPubMedGoogle Scholar
  • 47 Nader HB, Toma L, Pinhal MA, Bounassisi V, Colburn P, Dietrich CP. Effect of heparin and dextran sulfate on the synthesis and structure of heparan sulfate from cultured endothelial cells. Semin Thromb Hemost 1991; 17: 47-56
    PubMedGoogle Scholar
  • 48 Silva ME, Dietrich CP. Structure of Heparin: Characterization of the products formed from heparin by the action of a heparinase and a hepara-tinase from flavobacterium heparinum. J Biol Chem 1975; 250: 6841-6846
    PubMedGoogle Scholar
  • 49 Tobelem G. Endothelial cell interactions with heparin. Semin Thromb Hemost 1989; 15: 197-199
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 50 Kumar P, Kumar S, Marsden HB, Lynch PG, Eamshaw E. Weibel-Palade bodies in endothelial cells as a marker for angiogenesis in brain tumors. Cancer Res 1980; 40: 2010-2019
    PubMedGoogle Scholar
  • 51 Saksela O, Moscatelli D, Sommer A, Rifkin DB. Endothelial cell-derived heparan sulfate binds basic fibroblast growth factor and protects it from proteolytic degradation. J Cell Biol 1988; 107: 743-751
    CrossrefPubMedGoogle Scholar
  • 52 Sommer A, Rifkin DB. Interaction of heparin with human basic fibroblast growth factor: protection of the angiogenic protein from proteolytic degradation by a glycosaminoglycan. J Cell Physiol 1989; 138: 215-220
    CrossrefPubMedGoogle Scholar
  • 53 Damon DH, Lobb RR, D’Amore PA, Wagner JA. Heparin potentiates the action of acidic fibroblast growth factor by prolonging its biologic half-life. J Cell Physiol 1989; 138: 215-220
    CrossrefPubMedGoogle Scholar