Binding of von Willebrand Factor to Collagen and Glycoprotein Ibα, But Not to Glycoprotein IIb/IIIa, Contributes to Ischemic Stroke in Mice-Brief Report

被引：55

作者：

De Meyer, Simon F. ^{[1
,2
,3
,4
]}

Schwarz, Tobias ^{[5
]}

Deckmyn, Hans ^{[1
]}

Denis, Cecile V. ^{[6
]}

Nieswandt, Bernhard ^{[7
]}

Stoll, Guido ^{[5
]}

Vanhoorelbeke, Karen ^{[1
]}

Kleinschnitz, Christoph ^{[5
]}

机构：

[1] KULeuven, Lab Thrombosis Res, B-8500 Kortrijk, Belgium

[2] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA

[3] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA USA

[4] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[5] Univ Wurzburg, Dept Neurol, Wurzburg, Germany

[6] Univ Paris Sud, Inst Natl Sante & Rech Med, Unite 770, F-94275 Le Kremlin Bicetre, France

[7] Univ Wurzburg, Rudolf Virchow Ctr, Deutsch Forsch Gemeinschaft Res Ctr Expt Biomed, Chair Expt Biomed, Wurzburg, Germany

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2010年 / 30卷 / 10期

关键词：

ischemic stroke; von Willebrand factor; gene transfer; FACTOR-DEFICIENT MICE; THROMBUS FORMATION; TARGET; GENE; BLOCKADE;

D O I：

10.1161/ATVBAHA.110.208918

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective-To unravel crucial von Willebrand factor (VWF) interactions that are detrimental in stroke development. Methods and Results-VWF(-/-) mice received gene transfer to express mutants of VWF defective either in binding to fibrillar collagen, glycoprotein (GP) Ib alpha or GPIIb/IIIa, and underwent 60 minutes of transient middle cerebral artery occlusion. In VWF(-/-) mice reconstituted with VWF mutants defective in binding to collagen or GPIb alpha, protection against stroke was sustained, whereas VWF lacking the GPIIb/IIIa binding site restored full susceptibility similar to normal VWF. Conclusion-VWF-collagen and VWF-GPIb alpha (but not VWF-GPIIb/IIIa) interactions are instrumental in thrombus formation after transient middle cerebral artery occlusion, and their inhibition could be a promising target for stroke treatment. (Arterioscler Thromb Vasc Biol. 2010;30:1949-1951.)

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收藏

页码：1949 / 1951

页数：3

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