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Thromb Haemost 2001; 86(01): 164-171
DOI: 10.1055/s-0037-1616214
Research Article
Schattauer GmbH

Von Willebrand Factor Propeptide in Vascular Disorders

Jan A. van Mourik
1   Departments of Plasma Proteins and Blood Coagulation, CLB, Amsterdam
2   Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Thalia Romani de Wit
1   Departments of Plasma Proteins and Blood Coagulation, CLB, Amsterdam
› Author Affiliations
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Publication History

Publication Date:
12 December 2017 (online)

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Summary

Von Willebrand factor (VWF) is a multifunctional plasma protein that plays a prominent role in haemostasis. In endothelial cells, processing of its precursor pro-VWF results in the formation of two large polypeptides, mature VWF and a propeptide. These proteins are co-secreted on an equimolar basis but are cleared from the circulation at different rates. VWF levels are frequently elevated in response to vascular disorders. Similarly, propeptide levels are increased under these conditions, although primarily in fulminant vascular disease, such as thrombotic thrombocytopenic purpura and septicemia. In chronic vascular disease, e.g. diabetes or peripheral vascular disease, propeptide levels are much less elevated. The differential response of VWF and propeptide levels to vascular disease could provide a means to assess the extent and time course of endothelial cell activation. After secretion, the propeptide may play a role in modulating cellular adhesion processes. Thus, enhanced propeptide secretion seems not to be of merely diagnostic significance.

Key words

Von Willebrand factor - endothelial cells - von Willebrand factor propeptide - vascular disease - Weibel-Palade bodies
 

  • References

  • 1 Montgomery RR, Zimmerman TS. Von Willebrand‘s antigen II: a new plasma and platelet antigen deficient in severe von Willebrand‘s disease. J Clin Invest 1978; 62: 1498-507.
    PubMedGoogle Scholar
  • 2 McCarroll DR, Ruggeri ZM, Montgomery RR. Correlation between circulating levels of von Willebrand‘s antigen II and von Willebrand factor: discrimination between type I and type II von Willebrand‘s disease. J Lab Clin Med 1984; 103: 704-11.
    PubMedGoogle Scholar
  • 3 Verweij CL, Diergaarde P, Hart M, Pannekoek H. Full-length von Willebrand factor (VWF) cDNA encodes a highly repetitive protein, considerably larger than mature VWF subunit. EMBO J 1986; 5: 1839-47.
    PubMedGoogle Scholar
  • 4 Bonthron DT, Handin RI, Kaufman RJ, Wasley LC, Orr EC, Mitsock LM, Ewenstein B, Loscalzo J, Ginsberg D, Orkin SH. Structure of pre-pro von Willebrand factor and its expression in heterologous cells. Nature 1986; 324: 270-3.
    CrossrefPubMedGoogle Scholar
  • 5 Fay PJ, Kawai Y, Wagner DD, Ginsburg D, Bonthron D, Ohlsson-Wilhelm BM, Chavin SI, Abraham GN, Handin RI, Orkin SH, Montgomery RR, Marder VJ. Propolypeptide of von Willebrand factor circulates in blood and is identical to von Willebrand antigen II. Science 1986; 232: 995-8.
    CrossrefPubMedGoogle Scholar
  • 6 Mannucci PM. Von Willebrand factor, a marker of endothelial damage?. Arterioscler Thromb Vasc Biol 1998; 18: 1359-2.
    CrossrefPubMedGoogle Scholar
  • 7 Van Mourik JA, Boertjes R, Huisveld IA, Fijnvandraat K, Pajkrt D, van Genderen PJJ, Fijnheer R. Von Willebrand factor propeptide in vascular disorders: a tool to distinguish between acute and chronic endothelial cell perturbation. Blood 1999; 94: 179-85.
    PubMedGoogle Scholar
  • 8 Rubin DB, Wiener-Kronish JP, Murray JF, Green DR, Turner J, Luce JM, Montgomery AB, Marks JD, Matthay MA. Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome. J Clin Invest 1990; 86: 474-80.
    CrossrefPubMedGoogle Scholar
  • 9 Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635-41.
    CrossrefPubMedGoogle Scholar
  • 10 Qizilbash N, Duffy S, Prentice CRM, Boothby M, Warlow C. Von Willebrand factor and risk of ischemic stroke. Neurology 1997; 49: 1552-6.
    CrossrefPubMedGoogle Scholar
  • 11 Rumley A, Lowe GDO, Sweetnam PM, Yarnell JWG, Ford RP. Factor VIII von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study. Brit J Haematol 1999; 105: 110-6.
    CrossrefPubMedGoogle Scholar
  • 12 Goto S, Sakai H, Goto M, Ono M, Handa S, Ruggeri ZM. Enhanced shear-induced platelet aggregation in acute myocardial infarction. Circulation 1999; 99: 608-13.
    CrossrefPubMedGoogle Scholar
  • 13 Lip GYH, Blann A. Von Willebrand factor: a marker of endothelial dysfunction in vascular disorders?. Cardiovasc Res 1997; 34: 255-65.
    CrossrefPubMedGoogle Scholar
  • 14 Vischer UM, Ingerslev J, Wollheim CB, Mestries JC, Tsakiris DA, Haefeli WE, Kruithof EKO. Acute von Willebrand factor secretion from the endothelium in vivo: assessment through plasma propeptide (VWF:AgII) levels. Thromb Haemost 1997; 77: 387-93.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Van Buul-Wortelboer M, Brinkman HJ, Reinders JH, van Aken WG, van Mourik JA. Polar secretion of von Willebrand factor by endothelial cells. Biochim Biophys Acta 1989; 1011: 129-33.
    CrossrefPubMedGoogle Scholar
  • 16 Sporn LA, Marder VJ, Wagner DD. Differing polarity of the constitutive and regulated secretory pathways for von Willebrand factor in endothelial cells. J Cell Biol 1989; 108: 1283-9.
    CrossrefPubMedGoogle Scholar
  • 17 Wagner DD, Fay PJ, Sporn LA, Sinha S, Lawrence SO, Marder VJ. Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells. Proc Natl Acad Sci USA 1987; 84: 1955-9.
    CrossrefPubMedGoogle Scholar
  • 18 Sporn LA, Marder VJ, Wagner DD. Von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively. Blood 1987; 69: 1531-4.
    CrossrefPubMedGoogle Scholar
  • 19 Etingin OR, Silverstein RL, Hajjar DP. Von Willebrand factor mediates platelet adhesion to virally infected endothelial cells. Proc Natl Acad Sci USA 1993; 90: 5153-6.
    CrossrefPubMedGoogle Scholar
  • 20 André P, Denis CV, Ware J, Saffaripour S, Hynes RO, Ruggeri ZM, Wagner DD. Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins. Blood 2000; 96: 3322-8.
    PubMedGoogle Scholar
  • 21 Borchiellini A, Fijnvandraat K, ten Cate JW, Pajkrt D, van Deventer SJH, Pasterkamp G, Meijer-Huizinga F, Zwart-Huinink L, Voorberg J, van Mourik JA. Quantitative analysis of von Willebrand factor propeptide release in vivo: effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans. Blood 1996; 88: 2951-8.
    PubMedGoogle Scholar
  • 22 Blann AD, de Romeuf C, Mazurier C, McCollum CN. Circulating von Willebrand factor antigen II in atherosclerosis: a comparison with von Willebrand factor and soluble thrombomodulin. Blood Coagul Fibrinolysis 1998; 9: 261-6.
    CrossrefPubMedGoogle Scholar
  • 23 Vischer UM, Emeis JJ, Bilo HJG, Stehouwer CDA, Thomsen C, Rasmussen O, Hermansen K, Wollheim CB, Ingerslev J. VWF as a plasma marker of endothelial activation in diabetes: improved reliability with parallel determination of the VWF propeptide (VWF:AgII). Thromb Haemost 1998; 80: 1002-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Wagner DD. Cell biology of von Willebrand factor. Annu Rev Cell Biol 1990; 6: 217-46.
    CrossrefPubMedGoogle Scholar
  • 25 Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 1998; 67: 395-424.
    CrossrefPubMedGoogle Scholar
  • 26 Verwey CL, Hart M, Pannekoek H. Expression of variant von Willebrand factor (VWF) cDNA in heterologous cells: requirement of the pro-polypeptide in VWF multimer formation. EMBO J 1987; 6: 2885-90.
    PubMedGoogle Scholar
  • 27 Wise RJ, Pittman DD, Handin RI, Kaufman RJ, Orkin SH. The propeptide of von Willebrand factor independently mediates the assembly of von Willebrand multimers. Cell 1988; 52: 229-36.
    CrossrefPubMedGoogle Scholar
  • 28 Vischer U, Wagner DD. von Willebrand factor proteolytic processing and multimerization precede the formation of Weibel-Palade bodies. Blood 1994; 83: 3536-44.
    PubMedGoogle Scholar
  • 29 Sporn LA, Marder VJ, Wagner DD. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell 1986; 46: 185-90.
    CrossrefPubMedGoogle Scholar
  • 30 Levine JD, Harlan JM, Harker LA, Joseph ML, Counts RB. Thrombin-mediated release of factor VIII-related antigen from human umbilical vein endothelial cells in culture. Blood 1982; 60: 531-4.
    PubMedGoogle Scholar
  • 31 Loesberg C, Gonsalves MD, Zandbergen J, Willems Ch, van Aken WG, Stel HV, van Mourik JA, de Groot PG. The effect of calcium on the secretion of factor VIII-related antigen by cultured human endothelial cells. Biochim Biophys Acta 1983; 763: 160-8.
    CrossrefPubMedGoogle Scholar
  • 32 Hamilton KK, Sims PF. Changes in cytosolic Ca2+ associated with von Willebrand factor release in human endothelial cells exposed to histamine. Study of microcarrier cell monolayers using the fluorescent probe indo-1. J Clin Invest 1987; 79: 600-8.
    CrossrefPubMedGoogle Scholar
  • 33 Birch KA, Pober JS, Zavoico GB, Means AR, Ewenstein BM. Calcium/ calmodulin transduces trhombin-stimulated secretion: studies in intact and minimally permeabilized human umbilical vein endothelial cells. J Cell Biol 1992; 118: 1501-10.
    CrossrefPubMedGoogle Scholar
  • 34 Vischer UM, Wollheim CB. Purine nucleotides induce regulated secretion of von Willebrand factor: involvement of cytosolic Ca2+ and cyclic adenosine monophosphate-dependent signalling in endothelial exocytosis. Blood 1998; 91: 118-27.
    PubMedGoogle Scholar
  • 35 Hageman RJ, van den Eijnden-Schrauwen Y, Emeis JJ. Adenosine 3′:5′-cyclic monophosphate induces regulated secretion of tissue-type plasminogen activator and von Willebrand factor from cultured human endothelial cells. Thromb Haemost 1998; 79: 853-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 McCarroll DR, Ruggeri ZM, Montgomery RR. The effect of DDAVP on plasma levels of von Willebrand antigen II in normal individuals and patients with von Willebrand‘s disease. Blood 1984; 63: 532-5.
    PubMedGoogle Scholar
  • 37 De Romeuf C, Mazurier C. Comparison between von Willebrand factor (VWF) and VWF antigen II in normal individuals and patients with von Willebrand disease. Thromb Haemost 1998; 80: 37-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 De Jong SC, Stehouwer CDA, van den Berg M, Vischer UM, Rauwerda JA, Emeis JJ. Endothelial marker proteins in hyperhomocysteinemia. Thromb Haemost 1997; 78: 1332-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Gill JC, Endres-Brooks J, Bauer PJ, Marks Jr WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69: 1691-5.
    PubMedGoogle Scholar
  • 40 Sodetz JM, Paulson JC, McKee PA. Carbohydrate composition and identification of blood group A, B, and H oligosaccharide structures on human factor VIII/von Willebrand factor. J Biol Chem 1979; 254: 10754-60.
    PubMedGoogle Scholar
  • 41 Matsui T, Titani K, Mizuochi T. Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor: occurrence of blood group A,B, and H(O) structures. J Biol Chem 1992; 267: 8723-31.
    PubMedGoogle Scholar
  • 42 Matsui T, Shimoyama T, Matsumoto M, Fujimura Y, Takemoto Y, Sako M, Hamako J, Titani K. ABO blood group antigens on human plasma von Willebrand factor after ABO-mismatched bone marrow transplantation. Blood 1999; 94: 2895-900.
    PubMedGoogle Scholar
  • 43 Scott JP, Montgomery RR. Platelet von Willebrand‘s antigen II: active release by aggregating agents and a marker of platelet release reaction in vivo. Blood 1981; 58: 1075-80.
    PubMedGoogle Scholar
  • 44 Nichols TC, Samama CM, Bellinger DA, Roussi J, Reddick RL, Bonneau M, Read MS, Bailliart O, Koch GG, Vaiman M, Sigman JL, Pignaud GA, Brinkhous KM, Griggs TR, Drouet L. Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: Effect on arterial thrombosis in chimeras. Proc Natl Acad Sci USA 1995; 92: 2455-9.
    CrossrefPubMedGoogle Scholar
  • 45 Fijnheer R, Frijns CJM, Korteweg J, Rommes H, Peters JH, Sixma JJ, Nieuwenhuis HK. The origin of P-selectin as a circulating plasma protein. Thromb Haemost 1997; 77: 1081-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Blann A, Lip GYH, Gareth Beevers D, McCollum CN. Soluble P-selectin in atherosclerosis: a comparison with endothelial cell and platelet markers. Thromb Haemost 1997; 77: 1077-80.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Turecek PL, Pichler L, Auer W, Eder G, Varadi K, Mitterer A, Mundt W, Schlokat U, Drouet LO, Roussi J, van Mourik JA, Schwarz HP. Evidence for extracellular processing of pro-VWF after infusion in animals with and without severe von Willebrand disease. Blood 1999; 94: 1637-47.
    PubMedGoogle Scholar
  • 48 Reinders JH, de Groot PhG, Gonsalves 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; 803: 361-9.
    PubMedGoogle Scholar
  • 49 Sakai H, Goto S, Kim JY, Aoki N. Plasma concentration of von Willebrand factor in acute myocardial infarction. Thromb Haemost 2000; 84: 204-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 50 Jahroudi N, Lynch DC. Endothelial cell-specific regulation of von Willebrand factor gene expression. Mol Cell Biol 1994; 14: 999-1008.
    CrossrefPubMedGoogle Scholar
  • 51 Jahroudi N, Ardekani AM, Greenberger JS. Ionizing irradiation increases transcription of the von Willebrand factor gene in endothelial cells. Blood 1996; 88: 3801-14.
    PubMedGoogle Scholar
  • 52 Usui T, Takagi J, Saito Y. Propolypeptide of von Willebrand factor serves as a substrate for factor XIIIa and is cross-linked to laminin. J Biol Chem 1993; 268: 12311-6.
    PubMedGoogle Scholar
  • 53 Takagi J, Aoyama T, Ueki S, Ohba H, Saito Y, Lorand L. Identification of factor XIIIa-reactive glutaminyl residues in the propolypeptide of bovine von Willebrand factor. Eur J Biochem 1995; 232: 773-7.
    CrossrefPubMedGoogle Scholar
  • 54 Takagi J, Sudo Y, Saito T, Saito Y. Beta 1 integrin-mediated adhesion of melanoma cells to the propolypetide of von Willebrand factor. Eur J Biochem 1994; 222: 861-7.
    CrossrefPubMedGoogle Scholar
  • 55 Isobe T, Hisaoka T, Shimizu A, Okuno M, Aimoto S, Takada Y, Saito Y, Takagi J. Propolypeptide of von Willebrand factor is a novel ligand for very late antigen-4 integrin. J Biol Chem 1997; 272: 8447-53.
    CrossrefPubMedGoogle Scholar
  • 56 Takahashi H, Isobe T, Horibe S, Takagi J, Yokosaki Y, Sheppard D, Saito Y. Tissue transglutaminase, coagulation factor XIII, and the pro-polypeptide of von Willebrand factor are all ligands for the integrins 9 1 and 4 1. J Biol Chem 2000; 275: 23589-95.
    CrossrefPubMedGoogle Scholar
  • 57 Taooka Y, Chen J, Yednock T, Sheppard D. The integrin 9 1 mediates adhesion to activated endothelial cells and transendothelial neutrophil migration through interaction with vascular cell adhesion molecule-1. J Cell Biol 1999; 145: 413-20.
    CrossrefPubMedGoogle Scholar
  • 58 Mayadas TN, Wagner DD. Vicinal cysteines in the prosequence play a role in von Willebrand factor multimer assembly. Proc Natl Acad Sci USA 1992; 89: 3531-5.
    CrossrefPubMedGoogle Scholar
  • 59 Takagi J, Sekiya F, Kasahara K, Inada Y, Saito Y. Inhibition of platelet-collagen interaction by propolypeptide of von Willebrand factor. J Biol Chem 1989; 264: 6017-20.
    PubMedGoogle Scholar
  • 60 Takagi J, Kasahara K, Sekiya F, Inada Y, Saito Y. A collagen-binding glycoprotein from bovine platelets is identical to propolypeptide of von Willebrand factor. J Biol Chem 1989; 264: 10425-30.
    PubMedGoogle Scholar
  • 61 Ido Y, Vindigni A, Chang K, Stramm L, Chance R, Heath WF, DiMarch RD, Di Cera E, Williamson JR. Prevention of vascular and neural dysfunction in diabetic rats by C-peptide. Science 1997; 277: 563-6.
    CrossrefPubMedGoogle Scholar
  • 62 Wagner DD, Olmsted JB, Marder VJ. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol 1982; 95: 355-60.
    CrossrefPubMedGoogle Scholar
  • 63 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: 1423-33.
    CrossrefPubMedGoogle Scholar
  • 64 Bonfanti R, Furie BC, Furie B, Wagner DD. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood 1989; 73: 1109-12.
    PubMedGoogle Scholar
  • 65 Hattori R, Hamilton KK, Fugate RD, McEver RP, Sims PJ. Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem 1989; 264: 7768-71.
    PubMedGoogle Scholar
  • 66 McEver RP, Beckstead JH, Moore KL, Marshall-Carlson L, Bainton DF. GMP-140, a platelet α-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest 1989; 84: 92-9.
    CrossrefPubMedGoogle Scholar
  • 67 Vischer UM, Wagner DD. CD63 is a component of Weibel-Palade bodies of human endothelial cells. Blood 1993; 82: 1184-91.
    PubMedGoogle Scholar
  • 68 Russell FD, Skepper JN, Davenport AP. Evidence using immunelectron microscopy for regulated and constitutive pathways in the transport and release of endothelin. J Cardiovasc Pharm 1998; 31: 424-30.
    CrossrefPubMedGoogle Scholar
  • 69 Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G. Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of micro-vascular endothelial cells. J Exp Med 1998; 188: 1751-6.
    CrossrefPubMedGoogle Scholar
  • 70 Wolff B, Burns AR, Middleton J, Rot A. Endothelial cell "memory" of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies. J Exp Med 1998; 188: 1757-62.
    CrossrefPubMedGoogle Scholar
  • 71 Schnyder-Candrian S, Borsig L, Moser R, Berger EG. Localization of a 1,3-fucosyltransferase VI in Weibel-Palade bodies of human endothelial cells. Proc Natl Acad Sci USA 2000; 97: 8369-74.
    CrossrefPubMedGoogle Scholar
  • 72 Rosnoblet C, Vischer UM, Gerard RD, Irminger JC, Halban PA, Kruithof EK. Storage of tissue-type plasminogen activator in Weibel-Palade bodies of human endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 1796-803.
    CrossrefPubMedGoogle Scholar
  • 73 Emeis JJ, van den Eijnden-Schrauwen Y, van den Hoogen CM, de Priester W, Westmuckett A, Lupu F. An endothelial storage granule for tissue-type plasminogen activator. J Cell Biol 1997; 139: 245-56.
    CrossrefPubMedGoogle Scholar
  • 74 Van de Ven WJM, Voorberg J, Fontijn R, Pannekoek H, van den Ouwe-hand AMW, van Duijnhoven HLP, Roebroek AJM, Siezen RJ. Furin is a subtilisin-like proprotein processing enzyme in higher eukaryotes. Mol Biol Rep 1990; 14: 265-75.
    PubMedGoogle Scholar
  • 75 Wise RJ, Barr PJ, Wong PA, Kiefer MC, Brake AJ, Kaufman RJ. Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site. Proc Natl Acad Sci USA 1990; 87: 9378-82.
    CrossrefPubMedGoogle Scholar
  • 76 Laporte S, Denault JB, D’Orleans-Juste P, Leduc R. Presence of furin mRNA in cultured bovine endothelial cells and possible involvement of furin in the processing of the endothelin precursor. J Cardiovasc Pharm 1993; 22 (Suppl. 08) S7-10.
    PubMedGoogle Scholar
  • 77 De Leeuw HP. Small GTP-binding proteins and regulated secretion of von Willebrand factor by endothelial cells. PhD Thesis, University of Amsterdam 2000.
    PubMedGoogle Scholar