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)Ibα 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 GPIbα, protection against stroke was sustained, whereas VWF lacking the GPIIb/IIIa binding site restored full susceptibility similar to normal VWF. CONCLUSIONS: VWF-collagen and VWF-GPIbα (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.