Binding of von Willebrand factor to collagen and glycoprotein Ibalpha, 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.


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.
De Meyer
Simon F
SF
Laboratory for Thrombosis Research, KULeuven Campus Kortrijk, E Sabbelaan 53, B-8500 Kortrijk, Belgium. simon.demeyer@kuleuven-kortrijk.be
Schwarz
Tobias
T
Deckmyn
Hans
H
Denis
Cécile V
CV
Nieswandt
Bernhard
B
Stoll
Guido
G
Vanhoorelbeke
Karen
K
Kleinschnitz
Christoph
C
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020521:Stroke / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
D050505:Mutant Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D003094:Collagen