| First Author | Verhenne S | Year | 2015 |
| Journal | Blood | Volume | 126 |
| Issue | 14 | Pages | 1715-22 |
| PubMed ID | 26209660 | Mgi Jnum | J:230256 |
| Mgi Id | MGI:5755892 | Doi | 10.1182/blood-2015-03-632901 |
| Citation | Verhenne S, et al. (2015) Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice. Blood 126(14):1715-22 |
| abstractText | Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in alpha-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. |
