Thromb Haemost 2010; 104(03): 449-455
DOI: 10.1160/TH09-11-0777
Theme Issue Article
Schattauer GmbH

Regulation of von Willebrand factor-platelet interactions

Peter J. Lenting
1   INSERM U.770 and Univ. Paris-Sud, 94276, Le Kremlin-Bicêtre, France
,
Julie N. Pegon
1   INSERM U.770 and Univ. Paris-Sud, 94276, Le Kremlin-Bicêtre, France
,
Evelyn Groot
2   Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands
,
Philip G. de Groot
2   Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 16 November 2009

Accepted after minor revision: 15 April 2010

Publication Date:
23 November 2017 (online)

Summary

The formation of thrombi is a multistep process involving several components, including von Willebrand factor (VWF). VWF is an adhesive multimeric protein, which acts as a molecular bridge between the subendothelial matrix and the glycoprotein Ib/IX/V receptor complex. Furthermore, VWF promotes the expansion of the platelet plug by cross-linking platelets via binding to integrin αIIbβ3. In terms of thrombus formation, it is essential that VWF-platelet interactions occur timely, that is: it should happen not too early or too late. Given the co-existence of VWF and platelets in the circulation, this implies that there must be regulatory mechanisms that prevent premature formation of VWF-rich platelet aggregates that could occlude the vasculature. Indeed, several mechanisms have been identified at the level of VWF, which are dedicated to the prevention of excessive VWF-platelet interactions following endothelial release of VWF (which may include limited exposure to shear stress, the presence of Mg2+ ions, inhibition of VWF-platelet interactions by endothelial proteins, ADAMTS13-mediated proteolysis) and of circulating VWF-platelet aggregates during normal circulation (shielding of the platelet-binding A1 domain by other regions of the VWF molecule, inhibition of VWF-platelet interactions by β2-glycoprotein I). In the present review an overview of these mechanisms will be discussed.

 
  • References

  • 1 Vischer UM. von Willebrand factor, endothelial dysfunction, and cardiovascular disease. J Thromb Haemost 2006; 4: 1186-1193.
  • 2 Spiel AO, Gilbert JC, Jilma B. von Willebrand factor in cardiovascular disease: focus on acute coronary syndromes. Circulation 2008; 117: 1449-1459.
  • 3 Ruggeri ZM. Von Willebrand factor: looking back and looking forward. Thromb Haemost 2007; 98: 55-62.
  • 4 Chauhan AK, Kisucka J, Lamb CB. et al. von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins. Blood 2007; 109: 2424-2429.
  • 5 Takahashi M, Yamashita A, Moriguchi-Goto S. et al. Critical role of von Wille-brand factor and platelet interaction in venous thromboembolism. Histol Histopathol 2009; 24: 1391-1398.
  • 6 Feng S, Resendiz JC, Lu X. et al. Filamin A binding to the cytoplasmic tail of glycoprotein Ibalpha regulates von Willebrand factor-induced platelet activation. Blood 2003; 102: 2122-2129.
  • 7 Dai K, Bodnar R, Berndt MC. et al. A critical role for 14–3–3zeta protein in regulating the VWF binding function of platelet glycoprotein Ib-IX and its therapeutic implications. Blood 2005; 106: 1975-1981.
  • 8 Huang J, Roth R, Heuser JE. et al. Integrin alpha(v)beta(3) on human endothelial cells binds von Willebrand factor strings under fluid shear stress. Blood 2009; 113: 1589-1597.
  • 9 Turner NA, Nolasco L, Ruggeri ZM. et al. Endothelial cell ADAMTS-13 and VWF: production, release and VWF string cleavage. Blood 2009; 114: 5102-5111.
  • 10 Andre P, Denis CV, Ware J. et al. Platelets adhere to and translocate on von Wille-brand factor presented by endothelium in stimulated veins. Blood 2000; 96: 3322-3328.
  • 11 Motto DG, Chauhan AK, Zhu G. et al. Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice. J Clin Invest 2005; 115: 2752-2761.
  • 12 Dong JF, Moake JL, Nolasco L. et al. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 2002; 100: 4033-4039.
  • 13 Dong JF, Cruz MA, Aboulfatova K. et al. Magnesium maintains endothelial integrity, up-regulates proteolysis of ultra-large von Willebrand factor, and reduces platelet aggregation under flow conditions. Thromb Haemost 2008; 99: 586-593.
  • 14 Rondaij MG, Bierings R, Kragt A. et al. Dynamics and plasticity of Weibel-Palade bodies in endothelial cells. Arterioscler Thromb Vasc Biol 2006; 26: 1002-1007.
  • 15 Zannettino AC, Holding CA, Diamond P. et al. Osteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor. J Cell Physiol 2005; 204: 714-723.
  • 16 Shahbazi S, Lenting PJ, Fribourg C. et al. Characterization of the interaction between von Willebrand factor and osteoprotegerin. J Thromb Haemost 2007; 5: 1956-1962.
  • 17 Zhang X, Halvorsen K, Zhang CZ. et al. Mechanoenzymatic cleavage of the ultra-large vascular protein von Willebrand factor. Science 2009; 324: 1330-1334.
  • 18 Tsai HM. Mechanisms of microvascular thrombosis in thrombotic thrombocytopenic purpura. Kidney Int Suppl 2009; 112: S11-S14.
  • 19 Shim K, Anderson PJ, Tuley EA. et al. Platelet-VWF complexes are preferred substrates of ADAMTS13 under fluid shear stress. Blood 2008; 111: 651-657.
  • 20 Tsai HM, Nagel RL, Hatcher VB. et al. Multimeric composition of endothelial cell-derived von Willebrand factor. Blood 1989; 73: 2074-2076.
  • 21 Groot E, Fijnheer R, Sebastian SA. et al. The active conformation of von Wille-brand factor in patients with thrombotic thrombocytopenic purpura in remission. J Thromb Haemost 2009; 7: 962-969.
  • 22 Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339: 1585-1594.
  • 23 Furlan M, Robles R, Solenthaler M. et al. Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura. Blood 1998; 91: 2839-2846.
  • 24 Levy GG, Nichols WC, Lian EC. et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001; 413: 488-494.
  • 25 Siedlecki CA, Lestini BJ, Kottke-Marchant KK. et al. Shear-dependent changes in the three-dimensional structure of human von Willebrand factor. Blood 1996; 88: 2939-2950.
  • 26 Schneider SW, Nuschele S, Wixforth A. et al. Shear-induced unfolding triggers adhesion of von Willebrand factor fibers. Proc Natl Acad Sci USA 2007; 104: 7899-7903.
  • 27 Singh I, Shankaran H, Beauharnois ME. et al. Solution structure of human von Willebrand factor studied using small angle neutron scattering. J Biol Chem 2006; 281: 38266-38275.
  • 28 Savage B, Sixma JJ, Ruggeri ZM. Functional self-association of von Willebrand factor during platelet adhesion under flow. Proc Natl Acad Sci USA 2002; 99: 425-430.
  • 29 Shankaran H, Alexandridis P, Neelamegham S. Aspects of hydrodynamic shear regulating shear-induced platelet activation and self-association of von Wille-brand factor in suspension. Blood 2003; 101: 2637-2645.
  • 30 Ulrichts H, Vanhoorelbeke K, Girma JP. et al. The von Willebrand factor self-association is modulated by a multiple domain interaction. J Thromb Haemost 2005; 3: 552-561.
  • 31 Ulrichts H, Udvardy M, Lenting PJ. et al. Shielding of the A1 domain by the D’D3 domains of von Willebrand factor modulates its interaction with platelet glyco-protein Ib-IX-V. J Biol Chem 2006; 281: 4699-4707.
  • 32 Martin C, Morales LD, Cruz MA. Purified A2 domain of von Willebrand factor binds to the active conformation of von Willebrand factor and blocks the interaction with platelet glycoprotein Ibalpha. J Thromb Haemost 2007; 5: 1363-1370.
  • 33 Sodetz JM, Pizzo SV, McKee PA. Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. J Biol Chem 1977; 252: 5538-5546.
  • 34 Sodetz JM, Paulson JC, Pizzo SV. et al. Carbohydrate on human factor VIII/von Willebrand factor. Impairment of function by removal of specific galactose residues. J Biol Chem 1978; 253: 7202-7206.
  • 35 Kao KJ, Pizzo SV, McKee PA. Factor VIII/von Willebrand protein. Modification of its carbohydrate causes reduced binding to platelets. J Biol Chem 1980; 255: 10134-10139.
  • 36 Carew JA, Quinn SM, Stoddart JH. et al. O-linked carbohydrate of recombinant von Willebrand factor influences ristocetin-induced binding to platelet glycoprotein 1b. J Clin Invest 1992; 90: 2258-2267.
  • 37 Federici AB, De Romeuf C, de Groot PG. et al. Adhesive properties of the carbohydrate-modified von Willebrand factor (CHO-vWF). Blood 1988; 71: 947-952.
  • 38 Schulte am Esch J, Robson SC, Knoefel WT. et al. Impact of O-linked glycosylation of the VWF-A1-domain flanking regions on platelet interaction. Br J Haematol 2005; 128: 82-90.
  • 39 Cruz MA, Handin RI, Wise RJ. The interaction of the von Willebrand factor-A1 domain with platelet glycoprotein Ib/IX. The role of glycosylation and disulfide bonding in a monomeric recombinant A1 domain protein. J Biol Chem 1993; 268: 21238-21245.
  • 40 Vermylen J. More on: ‘new light on an old story: von Willebrand factor binding to collagen‘. J Thromb Haemost 2007; 5: 440-441.
  • 41 Ruggeri ZM, Orje JN, Habermann R. et al. Activation-independent platelet adhesion and aggregation under elevated shear stress. Blood 2006; 108: 1903-1910.
  • 42 Groot E, de Groot PG, Fijnheer R. et al. The presence of active von Willebrand factor under various pathological conditions. Curr Opin Hematol 2007; 14: 284-289.
  • 43 Federici AB, Mannucci PM. Management of inherited von Willebrand disease in 2007. Ann Med 2007; 39: 346-358.
  • 44 Hulstein JJ, de Groot PG, Silence K. et al. A novel nanobody that detects the gain-of-function phenotype of von Willebrand factor in ADAMTS13 deficiency and von Willebrand disease type 2B. Blood 2005; 106: 3035-3042.
  • 45 de Mast Q, Groot E, Lenting PJ. et al. Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria. J Infect Dis 2007; 196: 622-628.
  • 46 de Mast Q, Groot E, Asih PB. et al. ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria. Am J Trop Med Hyg 2009; 80: 492-498.
  • 47 van den Born BJ, van der Hoeven NV, Groot E. et al. Association between thrombotic microangiopathy and reduced ADAMTS13 activity in malignant hypertension. Hypertension 2008; 51: 862-866.
  • 48 Hulstein JJ, Runnard Heimel PJ, Franx A. et al. Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. J Thromb Haemost 2006; 4: 2569-2575.
  • 49 Hulstein JJ, Lenting PJ, de Laat B. et al. beta2-Glycoprotein I inhibits von Wille-brand factor dependent platelet adhesion and aggregation. Blood 2007; 110: 1483-1491.
  • 50 de Groot PG, Derksen RH. Pathophysiology of the antiphospholipid syndrome. J Thromb Haemost 2005; 3: 1854-1860.
  • 51 de Laat HB, Derksen RH, Urbanus RT. et al. beta2-glycoprotein I-dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome. Blood 2004; 104: 3598-3602.
  • 52 Miyakis S, Giannakopoulos B, Krilis SA. Beta 2 glycoprotein I--function in health and disease. Thromb Res 2004; 114: 335-346.
  • 53 de Laat B, de Groot PG, Derksen RH. et al. Association between beta2-glycoprotein I plasma levels and the risk of myocardial infarction in older men. Blood 2009; 114: 3656-3561.
  • 54 Lin F, Murphy R, White B. et al. Circulating levels of beta2-glycoprotein I in thrombotic disorders and in inflammation. Lupus 2006; 15: 87-93.
  • 55 Coppola R, Mari D, Lattuada A. et al. Von Willebrand factor in Italian centenarians. Haematologica 2003; 88: 39-43.
  • 56 Rayes J, Hollestelle MJ, Legendre P. et al. Mutation & ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B. Blood. 2010 preprint online.