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

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.)