While not essential for normal thrombosis and hemostasis, platelet- derived VWF fosters ischemic stroke injury in mice

Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in αgranules 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 < 0.01). Blocking of the platelet VWF-GPIb 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 GPIbdependent mechanism. For personal use only. on October 31, 2017. by guest www.bloodjournal.org From