title: Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice.
abstract: Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in α-granules of platelets and is enriched in hyperactive "ultra-large" VWF multimers. To elucidate the specific contribution of platelet VWF in hemostasis and thrombosis, we performed crossed bone marrow transplantations between C57BL/6J and Vwf(-/-) mice to generate chimeric mice. Chimeric mice specifically lacking platelet VWF showed normal tail bleeding and carotid artery thrombosis, similar to wild-type mice. Chimeric mice with VWF present only in platelets were not able to support normal thrombosis and hemostasis. However, using a mouse model of transient middle cerebral artery occlusion, we observed that cerebral infarct sizes and fibrin(ogen) deposition in chimeric mice with only platelet VWF were significantly increased compared with Vwf(-/-) mice (P < .01). Blocking of the platelet VWF-glycoprotein (GP)Ib interaction abrogated this platelet VWF-mediated injury. These data suggest that whereas platelet-derived VWF does not play a crucial role in hemostasis and arterial thrombosis, it aggravates thrombo-inflammatory diseases such as stroke via a GPIb-dependent mechanism.
authors.affiliation: Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;
authors.forename: Sebastien
authors.initials: S
authors.lastname: Verhenne
authors.affiliation: Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;
authors.forename: Frederik
authors.initials: F
authors.lastname: Denorme
authors.affiliation: Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;
authors.forename: Sarah
authors.initials: S
authors.lastname: Libbrecht
authors.affiliation: Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;
authors.forename: Aline
authors.initials: A
authors.lastname: Vandenbulcke
authors.affiliation: Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;
authors.forename: Inge
authors.initials: I
authors.lastname: Pareyn
authors.affiliation: Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;
authors.forename: Hans
authors.initials: H
authors.lastname: Deckmyn
authors.affiliation: Department of Radiotherapy, AZ Groeninge Campus Loofstraat, Kortrijk, Belgium;
authors.forename: Antoon
authors.initials: A
authors.lastname: Lambrecht
authors.affiliation: Rudolf Virchow Center, and.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: Department of Neurology, University Clinic of Wuerzburg, Wuerzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;
authors.forename: Karen
authors.initials: K
authors.lastname: Vanhoorelbeke
authors.affiliation: Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;
authors.forename: Simon F
authors.initials: SF
authors.lastname: De Meyer
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006487:Hemostasis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020521:Stroke / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism*; D018183:Transplantation Chimera; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor