S Kanaji1, S A Fahs, Q Shi, S L Haberichter, R R Montgomery. 1. Blood Research Institute, BloodCenter of Wisconsin, Department of Pediatrics, Medical College of Wisconsin, Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI 53226, USA. sachiko.kanaji@bcw.edu
Abstract
BACKGROUND: von Willebrand factor (VWF) is a glycoprotein that plays an important role in primary hemostasis. VWF is synthesized and stored in endothelial cells (ECs) and megakaryocytes/platelets. Plasma VWF is primarily derived from ECs and is generally believed to be essential for hemostasis. VWF synthesized in megakaryocytes is stored in platelet α-granules, from which it is released following platelet activation. The relative contribution of VWF stored in ECs or megakaryocytes/platelets or present in plasma to hemostasis is not clear. OBJECTIVES: We investigated whether EC-derived VWF plays the major role in hemostasis while the contribution of platelet-derived VWF is negligible, or if platelet-derived VWF also significantly contributes to hemostasis. METHODS AND RESULTS: Mice expressing VWF only in ECs (EC-VWF) or platelets (Plt-VWF) were created by reciprocal bone marrow transplantation between C57BL/6J (WT) and VWF knockout mice (VWF-/-). Plasma VWF levels in EC-VWF were similar to WT. Plt-VWF mice had a trace amount of VWF in their plasma while VWF levels in platelet lysate were comparable to WT. Tail bleeding time was normal in EC-VWF. Interestingly, Plt-VWF showed partially corrected bleeding time and significantly decreased blood loss volume compared with VWF-/-. Adhesion of platelets perfused over immobilized collagen under shear stress was significantly higher in both EC-VWF and Plt-VWF compared with VWF-/-. CONCLUSION: VWF synthesized in ECs is sufficient to support hemostasis in VWF-/- mice, and VWF produced in megakaryocytes/platelets can also contribute to hemostasis in the absence of EC-derived VWF.
BACKGROUND:von Willebrand factor (VWF) is a glycoprotein that plays an important role in primary hemostasis. VWF is synthesized and stored in endothelial cells (ECs) and megakaryocytes/platelets. Plasma VWF is primarily derived from ECs and is generally believed to be essential for hemostasis. VWF synthesized in megakaryocytes is stored in platelet α-granules, from which it is released following platelet activation. The relative contribution of VWF stored in ECs or megakaryocytes/platelets or present in plasma to hemostasis is not clear. OBJECTIVES: We investigated whether EC-derived VWF plays the major role in hemostasis while the contribution of platelet-derived VWF is negligible, or if platelet-derived VWF also significantly contributes to hemostasis. METHODS AND RESULTS:Mice expressing VWF only in ECs (EC-VWF) or platelets (Plt-VWF) were created by reciprocal bone marrow transplantation between C57BL/6J (WT) and VWF knockout mice (VWF-/-). Plasma VWF levels in EC-VWF were similar to WT. Plt-VWFmice had a trace amount of VWF in their plasma while VWF levels in platelet lysate were comparable to WT. Tail bleeding time was normal in EC-VWF. Interestingly, Plt-VWF showed partially corrected bleeding time and significantly decreased blood loss volume compared with VWF-/-. Adhesion of platelets perfused over immobilized collagen under shear stress was significantly higher in both EC-VWF and Plt-VWF compared with VWF-/-. CONCLUSION:VWF synthesized in ECs is sufficient to support hemostasis in VWF-/-mice, and VWF produced in megakaryocytes/platelets can also contribute to hemostasis in the absence of EC-derived VWF.
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