von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins

被引:89
作者
Chauhan, Anil K.
Kisucka, Janka
Lamb, Colin B.
Bergmeier, Wolfgang
Wagner, Denisa D.
机构
[1] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
关键词
D O I
10.1182/blood-2006-06-028241
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
von Willebrand factor (VWF) protects factor Vill (FVIII) from proteolysis and mediates the initial contact of platelets with the injured vessel wall, thus playing an important role in hemostasis and thrombosis. VWF is crucial for the formation of occlusive thrombi at arterial shear rates. However, with only a few conflicting studies published, the role of VWF in venous thrombosis is still unclear. Using gene-targeted mice, we show that in ferric chloride-injured veins platelet adhesion to subendothelium is decreased and thrombus growth is impaired in VWF-/- mice when compared with wild type (WT). We also observed increased embolization in the VWF-/- mice, which was due to lower FVIII levels in these mice as recombinant factor Vill (r-FVIII) restored thrombus stability. Despite normalization of blood clotting time and thrombus stability after r-FVIII infusion, the VWF-/- venules did not occlude. Transgenic platelets lacking the VWF receptor GPlb alpha extra-cellular domain showed decreased adhesion to injured veins. But, after a delay, all the injured venules occluded in these transgenic mice. Thus, VWIF likely uses other adhesion receptors besides GPIb alpha in thrombus growth under venous shear conditions. Our studies document crucial roles for VWIF and FVIII in experimental thrombosis under venous flow conditions in vivo.
引用
收藏
页码:2424 / 2429
页数:6
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