Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice.

Autor:	Verhenne S; Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;, Denorme F; Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;, Libbrecht S; Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;, Vandenbulcke A; Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;, Pareyn I; Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;, Deckmyn H; Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;, Lambrecht A; Department of Radiotherapy, AZ Groeninge Campus Loofstraat, Kortrijk, Belgium;, Nieswandt B; Rudolf Virchow Center, and., Kleinschnitz C; Department of Neurology, University Clinic of Wuerzburg, Wuerzburg, Germany., Vanhoorelbeke K; Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;, De Meyer SF; Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium;
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2015 Oct 01; Vol. 126 (14), pp. 1715-22. Date of Electronic Publication: 2015 Jul 24.
DOI:	10.1182/blood-2015-03-632901
Abstrakt:	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. (© 2015 by The American Society of Hematology.)
Databáze:	MEDLINE
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