title: Porcine and canine von Willebrand factor and von Willebrand disease: hemostasis, thrombosis, and atherosclerosis studies.
abstract: Use of animal models of inherited and induced von Willebrand factor (VWF) deficiency continues to advance the knowledge of VWF-related diseases: von Willebrand disease (VWD), thrombotic thrombocytopenic purpura (TTP), and coronary artery thrombosis. First, in humans, pigs, and dogs, VWF is essential for normal hemostasis; without VWF bleeding events are severe and can be fatal. Second, the ADAMTS13 cleavage site is preserved in all three species suggesting all use this mechanism for normal VWF multimer processing and that all are susceptible to TTP when ADAMTS13 function is reduced. Third, while the role of VWF in atherogenesis is debated, arterial thrombosis complicating atherosclerosis appears to be VWF-dependent. The differences in the VWF gene and protein between humans, pigs, and dogs are relatively few but important to consider in the design of VWF-focused experiments. These homologies and differences are reviewed in detail and their implications for research projects are discussed. The current status of porcine and canine VWD are also reviewed as well as their potential role in future studies of VWF-related disorders of hemostasis and thrombosis.
authors.affiliation: Department of Medicine, Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, NC 27516, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Nichols
authors.forename: Dwight A
authors.initials: DA
authors.lastname: Bellinger
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Merricks
authors.forename: Robin A
authors.initials: RA
authors.lastname: Raymer
authors.forename: Mark T
authors.initials: MT
authors.lastname: Kloos
authors.forename: Natalie
authors.initials: N
authors.lastname: Defriess
authors.forename: Margaret V
authors.initials: MV
authors.lastname: Ragni
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Griggs
references.citation: Blood. 2001 Jan 15;97(2):465-72
references.pmid: 11154224
references.citation: Nat Rev Drug Discov. 2007 Apr;6(4):273-86
references.pmid: 17396134
references.citation: Haemophilia. 2010 May;16 Suppl 3:24-8
references.pmid: 20586798
references.citation: Mayo Clin Proc. 1991 Jul;66(7):733-42
references.pmid: 2072761
references.citation: J Immunol. 1995 May 1;154(9):4565-75
references.pmid: 7722310
references.citation: Arterioscler Thromb Vasc Biol. 2002 Sep 1;22(9):1381-9
references.pmid: 12231555
references.citation: Arteriosclerosis. 1985 Jul-Aug;5(4):366-70
references.pmid: 3874619
references.citation: Circ Res. 1986 Jul;59(1):15-26
references.pmid: 3488139
references.citation: Circulation. 2007 Dec 4;116(23):2678-86
references.pmid: 18025536
references.citation: Proc Natl Acad Sci U S A. 1978 Sep;75(9):4514-8
references.pmid: 309134
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2455-9
references.pmid: 7708664
references.citation: Science. 2010 Jan 29;327(5965):580-3
references.pmid: 20110505
references.citation: J Thromb Haemost. 2006 Oct;4(10):2103-14
references.pmid: 16889557
references.citation: Am J Pathol. 1981 Feb;102(2):137-45
references.pmid: 6970527
references.citation: Circulation. 2004 Feb 17;109(6):740-4
references.pmid: 14970109
references.citation: Exp Hematol. 1996 Apr;24(5):585-91
references.pmid: 8605962
references.citation: Haematologica. 2000 May;85(5):514-9
references.pmid: 10800169
references.citation: ILAR J. 2009;50(2):144-67
references.pmid: 19293459
references.citation: Haemophilia. 2011 Nov;17(6):867-71
references.pmid: 21371197
references.citation: Proc Natl Acad Sci U S A. 1974 May;71(5):2087-90
references.pmid: 4546019
references.citation: Thromb Res. 2010 Mar;125(3):205-9
references.pmid: 19945154
references.citation: Proc Natl Acad Sci U S A. 1985 Dec;82(24):8752-6
references.pmid: 3936044
references.citation: J Thromb Haemost. 2009 Jul;7(7):1155-62
references.pmid: 19422452
references.citation: Blood. 2005 Dec 15;106(13):4199-209
references.pmid: 16131569
references.citation: J Thromb Haemost. 2005 Aug;3(8):1702-9
references.pmid: 16102036
references.citation: Thromb Res. 1989 Mar 1;53(5):417-26
references.pmid: 2499940
references.citation: Arterioscler Thromb Vasc Biol. 1999 Dec;19(12):3055-62
references.pmid: 10591687
references.citation: Blood. 2010 Nov 4;116(18):3653-9
references.pmid: 20644116
references.citation: Thromb Haemost. 1992 Mar 2;67(3):320-4
references.pmid: 1641822
references.citation: Arteriosclerosis. 1990 May-Jun;10(3):449-61
references.pmid: 2344301
references.citation: Platelets. 2007 May;18(3):182-98
references.pmid: 17497430
references.citation: ILAR J. 2006;47(3):243-58
references.pmid: 16804199
references.citation: Biochem Biophys Res Commun. 1992 Jan 31;182(2):561-8
references.pmid: 1370885
references.citation: J Clin Invest. 1985 Sep;76(3):1102-6
references.pmid: 2413071
references.citation: Gene Ther. 2008 Jun;15(11):870-5
references.pmid: 18432276
references.citation: Blood. 2008 Apr 1;111(7):3452-7
references.pmid: 18083848
references.citation: Arterioscler Thromb Vasc Biol. 1995 Jun;15(6):793-800
references.pmid: 7773736
references.citation: Arteriosclerosis. 1984 Mar-Apr;4(2):84-90
references.pmid: 6608347
references.citation: Haemophilia. 2006 Jul;12 Suppl 3:152-8
references.pmid: 16684011
references.citation: Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):1882-4
references.pmid: 20844269
references.citation: Haemophilia. 2008 Mar;14(2):171-232
references.pmid: 18315614
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3497-500
references.pmid: 12824352
references.citation: Am J Transplant. 2003 Sep;3(9):1065-75
references.pmid: 12919085
references.citation: Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1621-6
references.pmid: 18556568
references.citation: J Thromb Haemost. 2009 Jul;7(7):1152-4
references.pmid: 19426284
references.citation: J Lab Clin Med. 1983 Jan;101(1):74-82
references.pmid: 6600265
references.citation: Thromb Haemost. 1998 Aug;80(2):332-7
references.pmid: 9716162
references.citation: Blood. 1997 Nov 1;90(9):3555-67
references.pmid: 9345039
references.citation: N Engl J Med. 1999 Jan 14;340(2):115-26
references.pmid: 9887164
references.citation: Blood. 1988 Jul;72(1):308-13
references.pmid: 2898953
references.citation: Thromb Haemost. 1993 Nov 15;70(5):758-61
references.pmid: 8128431
references.citation: Am J Hematol. 1987 May;25(1):55-65
references.pmid: 3107374
references.citation: Thromb Haemost. 2010 Sep;104(3):563-70
references.pmid: 20589313
references.citation: Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3531-5
references.pmid: 1565649
references.citation: J Clin Invest. 1978 Dec;62(6):1255-63
references.pmid: 311783
references.citation: Blood. 1986 Sep;68(3):774-8
references.pmid: 3527303
references.citation: Circ Res. 1982 Nov;51(5):587-93
references.pmid: 6814782
references.citation: Blood. 2005 Jan 1;105(1):145-52
references.pmid: 15331450
references.citation: J Thromb Haemost. 2010 Jan;8(1):208-11
references.pmid: 19874455
references.citation: Thromb Res. 1977 Sep;11(3):345-55
references.pmid: 411191
references.citation: Blood. 2007 Jan 1;109(1):112-21
references.pmid: 16985174
references.citation: Blood Coagul Fibrinolysis. 1998 Jun;9(4):361-72
references.pmid: 9690808
references.citation: N Engl J Med. 2004 Aug 12;351(7):683-94
references.pmid: 15306670
references.citation: Transfusion. 2009 Oct;49(10):2181-5
references.pmid: 19538431
references.citation: J Clin Invest. 1986 Jul;78(1):26-30
references.pmid: 3088043
references.citation: J Thromb Haemost. 2005 Apr;3(4):775-7
references.pmid: 15842361
references.citation: Hereditas. 1996;124(2):199-202
references.pmid: 8782436
references.citation: Proc Natl Acad Sci U S A. 1987 Nov;84(22):8100-4
references.pmid: 3120185
references.citation: Blood. 1989 Aug 15;74(3):1031-5
references.pmid: 2473809
references.citation: J Clin Invest. 1988 Oct;82(4):1236-43
references.pmid: 2971673
references.citation: Blood. 2010 Jul 15;116(2):280-6
references.pmid: 20231421
references.citation: J Clin Invest. 2005 Oct;115(10):2752-61
references.pmid: 16200209
references.citation: Blood. 1979 Apr;53(4):712-9
references.pmid: 311643
references.citation: Arteriosclerosis. 1986 Mar-Apr;6(2):155-65
references.pmid: 3485423
references.citation: Blood. 1975 Feb;45(2):221-30
references.pmid: 1078981
references.citation: Proc Natl Acad Sci U S A. 1977 Feb;74(2):759-63
references.pmid: 300481
references.citation: Blood. 2003 Jul 15;102(2):436-41
references.pmid: 12649145
references.citation: Am J Physiol. 1976 May;230(5):1342-8
references.pmid: 776006
references.citation: Semin Thromb Hemost. 2010 Jul;36(5):510-21
references.pmid: 20635317
references.citation: J Lab Clin Med. 1992 Oct;120(4):553-8
references.pmid: 1402331
references.citation: Arterioscler Thromb Vasc Biol. 2003 Dec;23(12):2131-7
references.pmid: 14500287
references.citation: Blood. 2006 Jun 15;107(12):4728-36
references.pmid: 16478886
references.citation: Atherosclerosis. 1982 Jun;43(2-3):303-9
references.pmid: 6981417
references.citation: Haemophilia. 1998;4 Suppl 3:53-62
references.pmid: 10028320
references.citation: Blood. 2007 Mar 1;109(5):2267-8
references.pmid: 17312004
references.citation: Blood. 2006 Aug 1;108(3):862-9
references.pmid: 16638935
references.citation: J Clin Invest. 1978 Mar;61(3):722-30
references.pmid: 305924
references.citation: Structure. 2009 Nov 11;17(11):1476-84
references.pmid: 19913482
references.citation: Haemophilia. 2008 Sep;14(5):968-77
references.pmid: 18680527
references.citation: Blood. 2010 Jun 10;115(23):4870-7
references.pmid: 20200350
references.citation: Blood. 2010 Jun 10;115(23):4862-9
references.pmid: 20371742
references.citation: Platelets. 2009 Aug;20(5):334-40
references.pmid: 19637097
references.citation: Arteriosclerosis. 1985 Jan-Feb;5(1):67-73
references.pmid: 3871327
references.citation: Semin Thromb Hemost. 2010 Jul;36(5):522-8
references.pmid: 20632249
references.citation: Discov Med. 2010 Feb;9(45):105-11
references.pmid: 20193635
references.citation: Blood. 2008 Jul 1;112(1):11-8
references.pmid: 18574040
references.citation: Arteriosclerosis. 1987 Jan-Feb;7(1):47-54
references.pmid: 3545164
references.citation: Blood. 2000 Sep 1;96(5):1808-15
references.pmid: 10961880
references.citation: Biochemistry. 1986 Jun 3;25(11):3164-71
references.pmid: 3488076
references.citation: Blood. 1986 Jul;68(1):58-61
references.pmid: 3487361
references.citation: Am J Pathol. 1992 Feb;140(2):403-15
references.pmid: 1739133
references.citation: Transfusion. 2010 May;50(5):1079-87
references.pmid: 20070617
references.citation: Thromb Haemost. 1997 Jul;78(1):571-6
references.pmid: 9198218
references.citation: Circ J. 2010 Feb;74(2):213-20
references.pmid: 20065609
references.citation: Blood. 1991 May 1;77(9):1901-5
references.pmid: 1902120
references.citation: FASEB J. 1993 Feb 1;7(2):308-16
references.pmid: 8440408
references.citation: Blood. 1993 May 15;81(10):2644-51
references.pmid: 8490173
references.citation: J Lab Clin Med. 1970 Nov;76(5):713-21
references.pmid: 5312238