Table of Contents
Thrombosis
Volume 2010 (2010), Article ID 461238, 11 pages
http://dx.doi.org/10.1155/2010/461238
Review Article

Porcine and Canine von Willebrand Factor and von Willebrand Disease: Hemostasis, Thrombosis, and Atherosclerosis Studies

1Department of Medicine, Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, NC 27516, USA
2Pathology and Laboratory Medicine, Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, NC 27516, USA
3Division of Laboratory Animal Medicine, Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, NC 27516, USA
4Medicine/Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA
5Hemophilia Center of Western PA, Pittsburgh, PA 15213, USA

Received 27 October 2010; Accepted 29 December 2010

Academic Editor: David H. Farrell

Copyright © 2010 Timothy C. Nichols et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. E. Sadler, “Von Willebrand factor: two sides of a coin,” Journal of Thrombosis and Haemostasis, vol. 3, no. 8, pp. 1702–1709, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. T. R. Griggs, W. P. Webster, and H. A. Cooper, “Von Willebrand factor: gene dosage relationships and transfusion response in bleeder swine—a new bioassay,” Proceedings of the National Academy of Sciences of the United States of America, vol. 71, no. 5, pp. 2087–2090, 1974. View at Google Scholar · View at Scopus
  3. W. J. Dodds, “Canine von Willebrand's disease,” The Journal of Laboratory and Clinical Medicine, vol. 76, no. 5, pp. 713–721, 1970. View at Google Scholar · View at Scopus
  4. M. S. Read, R. W. Shermer, and K. M. Brinkhous, “Venom coagglutinin: an activator of platelet aggregation dependent on von Willebrand factor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 75, no. 9, pp. 4514–4518, 1978. View at Google Scholar · View at Scopus
  5. D. N. Fass, E. J. Bowie, C. A. Owen Jr., and P. E. Zollman, “Inheritance of porcine von Willbrand's disease: study of a kindred of over 700 pigs,” Blood, vol. 53, pp. 712–719, 1979. View at Google Scholar
  6. J. E. Sadler, U. Budde, J. C. J. Eikenboom et al., “Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand factor,” Journal of Thrombosis and Haemostasis, vol. 4, no. 10, pp. 2103–2114, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. M. V. Ragni, R. C. Jankowitz, H. L. Chapman et al., “A phase II prospective open-label escalating dose trial of recombinant interleukin-11 in mild von Willebrand disease,” Haemophilia, vol. 14, no. 5, pp. 968–977, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. T. C. Nichols, D. A. Bellinger, R. L. Reddick et al., “The roles of von Willebrand factor and factor VIII in arterial thrombosis: studies in canine von Willebrand disease and hemophilia A,” Blood, vol. 81, no. 10, pp. 2644–2651, 1993. View at Google Scholar · View at Scopus
  9. T. C. Nichols, C. M. Samama, D. A. Bellinger et al., “Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: effect on arterial thrombosis in chimeras,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 7, pp. 2455–2459, 1995. View at Publisher · View at Google Scholar
  10. T. C. Nichols, E. Merricks, E. M. Muchitsch et al., “Pharmacokinetics (PK) of rVWF in Dogs and Mice with VWD,” XXI ISTH Abstracts 2007:P-W-197.
  11. J. Roussi, P. L. Turecek, P. André et al., “Effects of human recombinant, plasma-derived and porcine von Willebrand factor in pigs with severe von Willebrand disease,” Blood Coagulation and Fibrinolysis, vol. 9, no. 4, pp. 361–372, 1998. View at Google Scholar · View at Scopus
  12. A. Sjöberg, W. T. Seaman, D. A. Bellinger, T. R. Griggs, T. C. Nichols, and B. P. Chowdhary, “FISH mapping of the porcine vWF gene to chromosome 5q21 extends synteny homology with human Chromosome 12,” Hereditas, vol. 124, no. 2, pp. 199–202, 1996. View at Publisher · View at Google Scholar · View at Scopus
  13. B. B. Shelton-Inloes, K. Titani, and J. E. Sadler, “cDNA sequences for human von Willebrand factor reveal five types of repeated domains and five possible protein sequence polymorphisms,” Biochemistry, vol. 25, no. 11, pp. 3164–3171, 1986. View at Google Scholar
  14. A. G. Hogan, M. E. Murhrer, and R. Bogart, “A hemophilia-like disease in swine,” Proceedings of The Society for Experimental Biology and Medicine, vol. 48, pp. 217–219, 1941. View at Google Scholar
  15. W. F. Bahou, E. J. W. Bowie, D. N. Fass, and D. Ginsburg, “Molecular genetic analysis of porcine von Willebrand disease: tight linkage to the von Willebrand factor locus,” Blood, vol. 72, no. 1, pp. 308–313, 1988. View at Google Scholar · View at Scopus
  16. R. Chenna, H. Sugawara, T. Koike et al., “Multiple sequence alignment with the Clustal series of programs,” Nucleic Acids Research, vol. 31, no. 13, pp. 3497–3500, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. B. R. Bahnak, J. M. Lavergne, V. Ferreira, D. Kerbiriou-Nabias, and D. Meyer, “Comparison of the primary structure of the functional domains of human and porcine von Willebrand factor that mediate platelet adhesion,” Biochemical and Biophysical Research Communications, vol. 182, no. 2, pp. 561–568, 1992. View at Google Scholar · View at Scopus
  18. S. A. Fahs, T. C. Nichols, D. A. Bellinger, and R. R. Montgomery, “Cloning and expression of full length recombinant porcine von Willebrand factor,” Journal of Thrombosis and Haemostasis, abstract no. OC277, 2003. View at Google Scholar
  19. W. Seaman, T. Griggs, and T. Nichols, “Sequence comparison of human and porcine vWF cDNA,” in Proceedings of the ASBMP/ASIP/AAI Joint Meeting, New Orleans, La, USA, 1996.
  20. T. N. Mayadas and D. D. Wagner, “Vicinal cysteines in the prosequence play a role in von Willebrand factor multimer assembly,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 8, pp. 3531–3535, 1992. View at Google Scholar · View at Scopus
  21. K. M. Brinkhous, B. D. Thomas, S. A. Ibrahim, and M. S. Read, “Plasma levels of platelet aggregating factor/von Willebrand factor in various species,” Thrombosis Research, vol. 11, no. 3, pp. 345–355, 1977. View at Google Scholar · View at Scopus
  22. M. S. Read, J. Y. Potter, and K. M. Brinkhous, “Venom coagglutinin for detection of von Willebrand factor activity in animal plasmas,” Journal of Laboratory and Clinical Medicine, vol. 101, no. 1, pp. 74–82, 1983. View at Google Scholar · View at Scopus
  23. M. J. Zurbano, G. Escolar, M. Heras, A. Ordinas, and R. Castillo, “Differential aspects of the glycoprotein Ib-von Willebrand factor axis in human and pig species,” Haematologica, vol. 85, no. 5, pp. 514–519, 2000. View at Google Scholar · View at Scopus
  24. V. H. Flood, J. C. Gill, P. A. Morateck et al., “Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor,” Blood, vol. 116, no. 2, pp. 280–286, 2010. View at Publisher · View at Google Scholar
  25. E. T. Mertz, “The anomaly of a normal Duke's and very prolonged saline bleeding time in swine suffering from an inherited bleeding disease,” American Journal of Physiology, vol. 136, pp. 360–362, 1942. View at Google Scholar
  26. W. P. Webster, S. R. Mandel, and L. E. Strike, “Factor VIII synthesis: hepatic and renal allografts in swine with von Willebrand's disease,” American Journal of Physiology, vol. 230, no. 5, pp. 1342–1348, 1976. View at Google Scholar
  27. E. J. W. Bowie, L. A. Solberg Jr., and D. N. Fass, “Transplantation of normal bone marrow into a pig with severe von Willebrand's disease,” Journal of Clinical Investigation, vol. 78, no. 1, pp. 26–30, 1986. View at Google Scholar
  28. J. Roussi, M. Samana, M. Vaiman et al., “An experimental model for testing von Willebrand factor function: successful SLA-matched crossed bone marrow transplantations between normal and von Willebrand pigs,” Experimental Hematology, vol. 24, no. 5, pp. 585–591, 1996. View at Google Scholar
  29. J.-P. Brouland, T. Egan, J. Roussi et al., “In vivo regulation of von Willebrand factor synthesis: von Willebrand factor production in endothelial cells after lung transplantation between normal pigs and von Willebrand factor-deficient pigs,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 12, pp. 3055–3062, 1999. View at Google Scholar
  30. K. M. Brinkhous, R. L. Reddick, M. S. Read, T. C. Nichols, D. A. Bellinger, and T. R. Griggs, “Von Willebrand factor and animal models: contributions to gene therapy, thrombotic thrombocytopenic purpura, and coronary artery thrombosis,” Mayo Clinic Proceedings, vol. 66, no. 7, pp. 733–742, 1991. View at Google Scholar · View at Scopus
  31. W. J. Dodds, “Further studies of canine von Willebrand's disease,” Blood, vol. 45, no. 2, pp. 221–230, 1975. View at Google Scholar · View at Scopus
  32. A. C. Goodeve, J. Eikenboom, G. Castaman et al., “Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD),” Blood, vol. 109, no. 1, pp. 112–121, 2007. View at Publisher · View at Google Scholar
  33. A. C. Goodeve, J. Eikenboom, G. Castaman et al., “Erratum: phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD) (Blood (2007) 109 (112–121)),” Blood, vol. 111, no. 6, pp. 3299–3300, 2008. View at Google Scholar
  34. W. L. Nichols, M. B. Hultin, A. H. James et al., “von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the national heart, lung, and blood institute (NHLBI) expert panel report (USA),” Haemophilia, vol. 14, no. 2, pp. 171–232, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. S. L. Haberichter, E. P. Merricks, S. A. Fahs, P. A. Christopherson, T. C. Nichols, and R. R. Montgomery, “Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells,” Blood, vol. 105, no. 1, pp. 145–152, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. S. L. Haberichter, S. A. Fahs, and R. R. Montgomery, “Von Willebrand factor storage and multimerization: 2 independent intracellular processes,” Blood, vol. 96, no. 5, pp. 1808–1815, 2000. View at Google Scholar · View at Scopus
  37. M. Rieger, H. P. Schwarz, P. L. Turecek, F. Dorner, J. A. Van Mourik, and C. Mannhalter, “Identification of mutations in the canine von Willebrand factor gene associated with type III von Willebrand disease,” Thrombosis and Haemostasis, vol. 80, no. 2, pp. 332–337, 1998. View at Google Scholar · View at Scopus
  38. M. S. Read, S. V. Smith, M. A. Lamb, and K. M. Brinkhous, “Role of botrocetin in platelet agglutination: formation of an activated complex of botrocetin and von Willebrand factor,” Blood, vol. 74, no. 3, pp. 1031–1035, 1989. View at Google Scholar · View at Scopus
  39. H. P. Schwarz, P. L. Turecek, L. Pichler et al., “Recombinant von Willebrand factor,” Thrombosis and Haemostasis, vol. 78, no. 1, pp. 571–576, 1997. View at Google Scholar · View at Scopus
  40. H. P. Schwarz, F. Dorner, A. Mitterer et al., “Evaluation of recombinant von Willebrand factor in a canine model of von Willebrand disease,” Haemophilia, vol. 4, no. 3, pp. 53–62, 1998. View at Publisher · View at Google Scholar · View at Scopus
  41. P. L. Turecek, H. Gritsch, L. Pichler et al., “In vivo characterization of recombinant von willebrand factor in dogs with von Willebrand disease,” Blood, vol. 90, no. 9, pp. 3555–3567, 1997. View at Google Scholar · View at Scopus
  42. P. L. Turecek, G. Schrenk, H. Rottensteiner et al., “Structure and function of a recombinant von willebrand factor drug candidate,” Seminars in Thrombosis and Hemostasis, vol. 36, no. 5, pp. 510–521, 2010. View at Publisher · View at Google Scholar
  43. K. M. Brinkhous, H. Sandberg, and J. B. Garris, “Purified human factor VIII procoagulant protein: comparative hemostatic response after infusions into hemophilic and von Willebrand disease dogs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 82, no. 24, pp. 8752–8756, 1985. View at Google Scholar
  44. E. H. N. Olsen, A. S. McCain, E. P. Merricks et al., “Comparative response of plasma VWF in dogs to up-regulation of VWF mRNA by interleukin-11 versus Weibel-Palade body release by desmopressin (DDAVP),” Blood, vol. 102, no. 2, pp. 436–441, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. T. R. Griggs, J. Potter, and S. B. McClanahan, “Macromolecular factor VIII complex: functional and structural heterogeneity observed in von Willebrand swine with transfusion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 74, no. 2, pp. 759–763, 1977. View at Google Scholar · View at Scopus
  46. T. Suiter, M. Laffan, P. M. Mannucci et al., “Recombinant human Von Willebrand Factor (rhVWF): first-in-human study evaluating pharmacokinetics, demonstrating safety and tolerability in type 3 Von Willebrand disease,” in Proceedings of the 52nd ASH Annual Meeting, 2010, Abstract 237.
  47. C. V. Denis, K. Kwack, S. Saffaripour et al., “Interleukin 11 significantly increases plasma von Willebrand factor and factor VIII in wild type and von Willebrand disease mouse models,” Blood, vol. 97, no. 2, pp. 465–472, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. A. B. Federici, G. Castaman, A. Thompson, and E. Berntorp, “Von Willebrand's disease: clinical management,” Haemophilia, vol. 12, no. 3, pp. 152–158, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. P. M. Mannucci, “Treatment of von Willebrand's disease,” New England Journal of Medicine, vol. 351, no. 7, pp. 683–694+730, 2004. View at Publisher · View at Google Scholar
  50. B. Jilma, P. Paulinska, P. Jilma-Stohlawetz, J. C. Gilbert, R. Hutabarat, and P. Knöbl, “A randomised pilot trial of the anti-von Willebrand factor aptamer ARC1779 in patients with type 2b von Willebrand disease,” Thrombosis and Haemostasis, vol. 104, no. 3, pp. 563–570, 2010. View at Publisher · View at Google Scholar
  51. J. E. Sadler and F. Rodeghiero, “Provisional criteria for the diagnosis of VWD type 1,” Journal of Thrombosis and Haemostasis, vol. 3, no. 4, pp. 775–777, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. R. Ross, “Atherosclerosis—an inflammatory disease,” New England Journal of Medicine, vol. 340, no. 2, pp. 115–126, 1999. View at Publisher · View at Google Scholar
  53. J. Folkman, “Angiogenesis: an organizing principle for drug discovery?” Nature Reviews Drug Discovery, vol. 6, no. 4, pp. 273–286, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. P. Libby, Y. Okamoto, V. Z. Rocha, and E. Folco, “Inflammation in atherosclerosis: transition from theory to practice,” Circulation Journal, vol. 74, no. 2, pp. 213–220, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. D. A. Bellinger, E. P. Merricks, and T. C. Nichols, “Swine models of type 2 diabetes mellitus: insulin resistance, glucose tolerance, and cardiovascular complications,” ILAR Journal, vol. 47, no. 3, pp. 243–258, 2006. View at Google Scholar · View at Scopus
  56. V. Fuster, J. T. Lie, and L. Badimon, “Spontaneous and diet-induced coronary atherosclerosis in normal swine and swine with von Willebrand disease,” Arteriosclerosis, vol. 5, no. 1, pp. 67–73, 1985. View at Google Scholar · View at Scopus
  57. L. Badimon, P. Steele, and J. J. Badimon, “Aortic atherosclerosis in pigs with heterozygous von Willebrand disease. Comparison with homozygous von Willebrand and normal pigs,” Arteriosclerosis, vol. 5, no. 4, pp. 366–370, 1985. View at Google Scholar · View at Scopus
  58. V. Fuster, D. N. Fass, and M. P. Kaye, “Arteriosclerosis in normal and von Willebrand pigs. Long-term prospective study and aortic transplantation study,” Circulation Research, vol. 51, no. 5, pp. 587–593, 1982. View at Google Scholar · View at Scopus
  59. W. Fuster, E. J. Bowie, J. C. Lewis, D. N. Fass, C. A. Owen, and A. L. Brown, “Resistance to arteriosclerosis in pigs with von Willebrand's disease. Spontaneous and high cholesterol diet-induced arteriosclerosis,” Journal of Clinical Investigation, vol. 61, no. 3, pp. 722–730, 1978. View at Google Scholar · View at Scopus
  60. T. R. Griggs, R. L. Reddick, D. Sultzer, and K. M. Brinkhous, “Susceptibility to atherosclerosis in aortas and coronary arteries of swine with von Willebrand's disease,” American Journal of Pathology, vol. 102, no. 2, pp. 137–145, 1981. View at Google Scholar · View at Scopus
  61. D. L. Sultzer, K. M. Brinkhous, R. L. Reddick, and T. R. Griggs, “Effect of carbon monoxide on atherogenesis in normal pigs and pigs with von Willebrand's disease,” Atherosclerosis, vol. 43, no. 2-3, pp. 303–319, 1982. View at Google Scholar · View at Scopus
  62. M. A. Lamb, J. E. Manning, R. L. Reddick, and T. R. Griggs, “Smooth muscle cell proliferation in response to endothelial injury in coronary arteries of normal and von Willebrand's disease swine,” Arteriosclerosis, vol. 4, no. 2, pp. 84–90, 1984. View at Google Scholar · View at Scopus
  63. T. R. Griggs, R. W. Bauman, and R. L. Reddick, “Development of coronary atherosclerosis in swine with severe hypercholesterolemia. Lack of influence of von Willebrand factor or acute intimal injury,” Arteriosclerosis, vol. 6, no. 2, pp. 155–165, 1986. View at Google Scholar · View at Scopus
  64. T. C. Nichols, D. A. Bellinger, D. A. Tate et al., “Von Willebrand factor and occlusive arterial thrombosis. A study in normal and von Willebrand's disease pigs with diet-induced hypercholesterolemia and atherosclerosis,” Arteriosclerosis, vol. 10, no. 3, pp. 449–461, 1990. View at Google Scholar · View at Scopus
  65. T. C. Nichols, D. A. Bellinger, K. E. Davis et al., “Porcine von Willebrand disease and atherosclerosis: influence of polymorphism in apolipoprotein B100 genotype,” American Journal of Pathology, vol. 140, no. 2, pp. 403–415, 1992. View at Google Scholar · View at Scopus
  66. A. B. Federici, P. M. Mannucci, E. Fogato, P. Ghidoni, and L. Matturri, “Autopsy findings in three patients with von Willebrand disease type IIB and type III: presence of atherosclerotic lesions without occlusive arterial thrombi,” Thrombosis and Haemostasis, vol. 70, no. 5, pp. 758–761, 1993. View at Google Scholar · View at Scopus
  67. A. Šrámek, P. Bucciarelli, A. B. Federici et al., “Patients with type 3 severe von Willebrand disease are not protected against atherosclerosis: results from a multicenter study in 47 patients,” Circulation, vol. 109, no. 6, pp. 740–744, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. T. C. Nichols, D. A. Bellinger, and T. A. Johnson, “Von Willebrand's disease prevents occlusive thrombosis in stenosed and injured porcine coronary arteries,” Circulation Research, vol. 59, no. 1, pp. 15–26, 1986. View at Google Scholar · View at Scopus
  69. D. A. Bellinger, T. C. Nichols, M. S. Read et al., “Prevention of occlusive coronary artery thrombosis by a murine monoclonal antibody to porcine von Willebrand factor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 22, pp. 8100–8104, 1987. View at Google Scholar · View at Scopus
  70. J. L. Diener, H. A. Daniel Lagassé, D. Duerschmied et al., “Inhibition of von Willebrand factor-mediated platelet activation and thrombosis by the anti-von Willebrand factor A1-domain aptamer ARC1779,” Journal of Thrombosis and Haemostasis, vol. 7, no. 7, pp. 1155–1162, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. P. M. Mannucci, “Platelet/von Willebrand factor inhibitors to the rescue of ischemic stroke,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 10, pp. 1882–1884, 2010. View at Publisher · View at Google Scholar
  72. J. C. Gilbert, T. DeFeo-Fraulini, R. M. Hutabarat et al., “First-in-human evaluation of anti-von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers,” Circulation, vol. 116, no. 23, pp. 2678–2686, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. R. H. Huang, D. H. Fremont, J. L. Diener, R. G. Schaub, and J. E. Sadler, “A structural explanation for the antithrombotic activity of ARC1172, a DNA aptamer that binds von Willebrand factor domain A1,” Structure, vol. 17, no. 11, pp. 1476–1484, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. A. O. Spiel, F. B. Mayr, N. Ladani et al., “The aptamer ARC1779 is a potent and specific inhibitor of von willebrand factor mediated ex vivo platelet function in acute myocardial infarction,” Platelets, vol. 20, no. 5, pp. 334–340, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Laffan and T. A. J. Mckinnon, “Blocking von Willebrand factor: a novel anti-platelet therapy,” Journal of Thrombosis and Haemostasis, vol. 7, no. 7, pp. 1152–1154, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. J. A. Koedam, J. C. M. Meijers, J. J. Sixma, and B. N. Bouma, “Inactivation of human Factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor,” Journal of Clinical Investigation, vol. 82, no. 4, pp. 1236–1243, 1988. View at Google Scholar · View at Scopus
  77. D. M. Monroe, M. Hoffman, and H. R. Roberts, “Platelets and thrombin generation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 22, no. 9, pp. 1381–1389, 2002. View at Publisher · View at Google Scholar · View at Scopus
  78. K. M. Brinkhous, R. L. Reddick, and T. R. Griggs, “Arterial thrombosis, atherosclerosis, and the factor VIII/von Willebrand factor complex,” in Coagulation and Bleeding Disorders: The Role of Factor VIII and von Willebrand Factor, T. S. Zimmerman and Z. M. Ruggeri, Eds., vol. 9, pp. 283–303, Marcel Dekker, New York, NY, USA, 1989. View at Google Scholar
  79. C. J. Foley, L. Nichols, K. Jeong, C. G. Moore, and M. V. Ragni, “Coronary atherosclerosis and cardiovascular mortality in hemophilia,” Journal of Thrombosis and Haemostasis, vol. 8, no. 1, pp. 208–211, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. M. V. Ragni and C. G. Moore, “Atherosclerotic heart diesease in hemophilia: prevalence and predictors,” Haemophilia, in press.
  81. Z. M. Ruggeri and J. Ware, “von Willebrand factor,” FASEB Journal, vol. 7, no. 2, pp. 308–316, 1993. View at Google Scholar
  82. Q. Y. Wu, L. Drouet, and J. L. Carrier, “Differential distribution of von Willebrand factor in endothelial cells. Comparison between normal pigs and pigs with von Willebrand disease,” Arteriosclerosis, vol. 7, no. 1, pp. 47–54, 1987. View at Google Scholar
  83. J. Koutts, P. N. Walsh, and E. F. Plow, “Active release of human platelet factor VIII related antigen by adenosine diphosphate, collagen, and thrombin,” Journal of Clinical Investigation, vol. 62, no. 6, pp. 1255–1263, 1978. View at Google Scholar
  84. L. A. Sporn, S. I. Chavin, V. J. Marder, and D. D. Wagner, “Biosynthesis of von Willebrand protein by human megakaryocytes,” Journal of Clinical Investigation, vol. 76, no. 3, pp. 1102–1106, 1985. View at Google Scholar · View at Scopus
  85. E. M. Cramer, J. P. Caen, L. Drouet, and J. Breton-Gorius, “Absence of tubular structures and immunolabeling for von Willebrand factor in the platelet α-granules from porcine von Willebrand disease,” Blood, vol. 68, no. 3, pp. 774–778, 1986. View at Google Scholar · View at Scopus
  86. H. R. Gralnick, M. E. Rick, and L. P. McKeown, “Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease,” Blood, vol. 68, no. 1, pp. 58–61, 1986. View at Google Scholar
  87. R. I. Parker, L. P. McKeown, J. I. Gallin, and H. R. Gralnick, “Absence of the largest platelet-von Willebrand multimers in a patient with lactoferrin deficiency and a bleeding tendency,” Thrombosis and Haemostasis, vol. 67, no. 3, pp. 320–324, 1992. View at Google Scholar · View at Scopus
  88. P. M. Mannucci, M. Moia, and P. Rebulla, “Correction of the bleeding time in treated patients with severe von Willebrand disease is not solely dependent on the normal multimeric structure of plasma von Willebrand factor,” American Journal of Hematology, vol. 25, no. 1, pp. 55–65, 1987. View at Google Scholar
  89. R. K. Smiley, P. Tittley, and G. Rock, “Studies on the prolonged bleeding time in von Willebrand's Disease,” Thrombosis Research, vol. 53, no. 5, pp. 417–426, 1989. View at Google Scholar · View at Scopus
  90. R. Castillo, J. Monteagudo, G. Escolar, A. Ordinas, M. Magallon, and J. M. Villar, “Hemostatic effect of normal platelet transfusion in severe von Willebrand disease patients,” Blood, vol. 77, no. 9, pp. 1901–1905, 1991. View at Google Scholar · View at Scopus
  91. W. P. Webster, S. R. Mandel, and L. E. Strike, “Factor VIII synthesis: hepatic and renal allografts in swine with von Willebrand's disease,” American Journal of Physiology, vol. 230, no. 5, pp. 1342–1348, 1976. View at Google Scholar
  92. N. C. Hasbrouck and K. A. High, “AAV-mediated gene transfer for the treatment of hemophilia B: problems and prospects,” Gene Therapy, vol. 15, no. 11, pp. 870–875, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. P. Margaritis and K. A. High, “Gene therapy in haemophilia—going for cure?” Haemophilia, vol. 16, no. 3, pp. 24–28, 2010. View at Publisher · View at Google Scholar · View at Scopus
  94. R. W. Herzog, O. Cao, and A. Srivastava, “Two decades of clinical gene therapy—success is finally mounting,” Discovery medicine, vol. 9, no. 45, pp. 105–111, 2010. View at Google Scholar · View at Scopus
  95. S. F. De Meyer, K. Vanhoorelbeke, M. K. Chuah et al., “Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor,” Blood, vol. 107, no. 12, pp. 4728–4736, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. R. G. Pergolizzi, G. Jin, D. Chan et al., “Correction of a murine model of von Willebrand disease by gene transfer,” Blood, vol. 108, no. 3, pp. 862–869, 2006. View at Publisher · View at Google Scholar · View at Scopus
  97. S. F. De Meyer, N. Vandeputte, I. Pareyn et al., “Restoration of plasma von willebrand factor deficiency is sufficient to correct thrombus formation after gene therapy for severe von willebrand disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 9, pp. 1621–1626, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. T. C. Nichols, A. M. Dillow, H. W. G. Franck et al., “Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von Willebrand disease, and factor VII deficiency,” ILAR Journal, vol. 50, no. 2, pp. 144–167, 2009. View at Google Scholar · View at Scopus
  99. Z. E. Holzknecht and J. L. Platt, “Identification of porcine endothelial cell membrane antigens recognized by human xenoreactive natural antibodies,” Journal of Immunology, vol. 154, no. 9, pp. 4565–4575, 1995. View at Google Scholar · View at Scopus
  100. C. L. Lau, E. Cantu III, G. V. Gonzalez-Stawinski et al., “The role of antibodies and von Willebrand factor in discordant pulmonary xenotransplantation,” American Journal of Transplantation, vol. 3, no. 9, pp. 1065–1075, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. J. E. Sadler, “Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura,” Blood, vol. 112, no. 1, pp. 11–18, 2008. View at Publisher · View at Google Scholar · View at Scopus
  102. W. E. Sanders Jr., R. L. Reddick, T. C. Nichols, K. M. Brinkhous, and M. S. Read, “Thrombotic thrombocytopenia induced in dogs and pigs: the role of plasma and platelet vWF in animal models of thrombotic thrombocytopenic purpura,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 15, no. 6, pp. 793–800, 1995. View at Google Scholar · View at Scopus
  103. L. H. Nolasco, N. A. Turner, A. Bernardo et al., “Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers,” Blood, vol. 106, no. 13, pp. 4199–4209, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. D. G. Motto, A. K. Chauhan, G. Zhu et al., “Shigatoxin triggers thrombic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice,” Journal of Clinical Investigation, vol. 115, no. 10, pp. 2752–2761, 2005. View at Publisher · View at Google Scholar
  105. A. K. Chauhan, M. T. Walsh, G. Zhu, D. Ginsburg, D. D. Wagner, and D. G. Motto, “The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis,” Blood, vol. 111, no. 7, pp. 3452–3457, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. J. Huang, D. G. Motto, D. R. Bundle, and J. E. Sadler, “Shiga toxin B subunits induce VWF secretion by human endothelial cells and thrombotic microangiopathy in ADAMTS13-deficient mice,” Blood, vol. 116, no. 18, pp. 3653–3659, 2010. View at Publisher · View at Google Scholar
  107. E.-M. Muchitsch, B. Dietrich, H. Rottensteiner et al., “Preclinical testing of human recombinant von willebrand factor: ADAMTS13 cleavage capacity in animals as criterion for species suitability,” Seminars in Thrombosis and Hemostasis, vol. 36, no. 5, pp. 522–528, 2010. View at Publisher · View at Google Scholar
  108. P. Knöbl, B. Jilma, J. C. Gilbert, R. M. Hutabarat, P. G. Wagner, and P. Jilma-Stohlawetz, “Anti-von Willebrand factor aptamer ARC1779 for refractory thrombotic thrombocytopenic purpura,” Transfusion, vol. 49, no. 10, pp. 2181–2185, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. F. B. Mayr, P. Knöbl, B. Jilma et al., “The aptamer ARC1779 blocks von Willebrand factor-dependent platelet function in patients with thrombotic thrombocytopenic purpura ex vivo,” Transfusion, vol. 50, no. 5, pp. 1079–1087, 2010. View at Publisher · View at Google Scholar · View at Scopus
  110. C. M. Johnson and E. J. W. Bowie, “Pigs with von Willebrand disease may be resistant to experimental infective endocarditis,” Journal of Laboratory and Clinical Medicine, vol. 120, no. 4, pp. 553–558, 1992. View at Google Scholar · View at Scopus
  111. L. M. Beaulieu and J. E. Freedman, “The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes,” Thrombosis Research, vol. 125, no. 3, pp. 205–209, 2010. View at Publisher · View at Google Scholar · View at Scopus
  112. D. D. Wagner and P. C. Burger, “Platelets in inflammation and thrombosis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 12, pp. 2131–2137, 2003. View at Publisher · View at Google Scholar · View at Scopus
  113. E. Boilard, P. A. Nigrovic, K. Larabee et al., “Platelets amplify inflammation in arthritis via collagen-dependent microparticle production,” Science, vol. 327, no. 5965, pp. 580–583, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Golder, C. M. Pruss, C. Hegadorn et al., “Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions,” Blood, vol. 115, no. 23, pp. 4862–4869, 2010. View at Publisher · View at Google Scholar
  115. J. Rayes, M. J. Hollestelle, P. Legendre et al., “Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B,” Blood, vol. 115, no. 23, pp. 4870–4877, 2010. View at Publisher · View at Google Scholar
  116. M. S. Chitta, R. J. Duhé, and J. C. Kermode, “Cloning of the cDNA for murine von Willebrand factor and identification of orthologous genes reveals the extent of conservation among diverse species,” Platelets, vol. 18, no. 3, pp. 182–198, 2007. View at Publisher · View at Google Scholar · View at Scopus
  117. P. J. Lenting, P. G. de Groot, S. F. De Meyer et al., “Correction of the bleeding time in von Willebrand factor (VWF)-deficient mice using murine VWF,” Blood, vol. 109, no. 5, pp. 2267–2268, 2007. View at Publisher · View at Google Scholar · View at Scopus