Binding of von Willebrand factor to collagen and glycoprotein Ib??, but not to glycoprotein IIb/IIIa, contributes to ischemic stroke in mice-brief report

  • De Meyer S
  • Schwarz T
  • Deckmyn H
 et al. 
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Abstract

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.

Author-supplied keywords

  • gene transfer
  • ischemic stroke
  • von Willebrand factor

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Authors

  • Simon F. De Meyer

  • Tobias Schwarz

  • C??cile V. Denis

  • Bernhard Nieswandt

  • Guido Stoll

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