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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / metabolism
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Brain / pathology
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Brain Ischemia / etiology*
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Brain Ischemia / genetics
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Brain Ischemia / metabolism*
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Brain Ischemia / pathology
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Collagen / metabolism*
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Disease Models, Animal
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Mutant Proteins / genetics
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Mutant Proteins / metabolism
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Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
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Platelet Glycoprotein GPIb-IX Complex / metabolism*
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Protein Binding
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Stroke / etiology*
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Stroke / genetics
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Stroke / metabolism*
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Stroke / pathology
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von Willebrand Factor / genetics
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von Willebrand Factor / metabolism*
Substances
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Mutant Proteins
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Platelet Glycoprotein GPIIb-IIIa Complex
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Platelet Glycoprotein GPIb-IX Complex
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Recombinant Proteins
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von Willebrand Factor
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Collagen