TY - JOUR
T1 - Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice
AU - Verhenne, Sebastien
AU - Denorme, Frederik
AU - Libbrecht, Sarah
AU - Vandenbulcke, Aline
AU - Pareyn, Inge
AU - Deckmyn, Hans
AU - Lambrecht, Antoon
AU - Nieswandt, Bernhard
AU - Kleinschnitz, Christoph
AU - Vanhoorelbeke, Karen
AU - De Meyer, Simon F.
N1 - Publisher Copyright:
© 2015 by The American Society of Hematology.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in a-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.
AB - Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in a-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.
UR - https://www.scopus.com/pages/publications/84947997089
U2 - 10.1182/blood-2015-03-632901
DO - 10.1182/blood-2015-03-632901
M3 - Article
C2 - 26209660
AN - SCOPUS:84947997089
SN - 0006-4971
VL - 126
SP - 1715
EP - 1722
JO - Blood
JF - Blood
IS - 14
ER -