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.

journal_name

Blood

journal_title

Blood

authors

Verhenne S,Denorme F,Libbrecht S,Vandenbulcke A,Pareyn I,Deckmyn H,Lambrecht A,Nieswandt B,Kleinschnitz C,Vanhoorelbeke K,De Meyer SF

doi

10.1182/blood-2015-03-632901

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

1715-22

issue

14

eissn

0006-4971

issn

1528-0020

pii

blood-2015-03-632901

journal_volume

126

pub_type

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