Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis
| Autor: | Ulrich Budde, Marcus Stockschlaeder, Reinhard Schneppenheim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities high-molecular-weight multimers von Willebrand factor Platelet membrane glycoprotein Platelet Adhesiveness Von Willebrand factor Platelet adhesiveness hemic and lymphatic diseases Von Willebrand disease medicine Animals Humans Platelet Review Articles chemistry.chemical_classification Hemostasis biology Chemistry Hematology General Medicine medicine.disease ADAMTS13 Cell biology von Willebrand Diseases factor VIII Immunology platelets biology.protein cardiovascular system Glycoprotein von Willebrand disease circulatory and respiratory physiology |
| Zdroj: | Blood Coagulation & Fibrinolysis |
| ISSN: | 1473-5733 0957-5235 |
| Popis: | Normal hemostasis requires von Willebrand factor (VWF) to support platelet adhesion and aggregation at sites of vascular injury. VWF is a multimeric glycoprotein built from identical subunits that contain binding sites for both platelet glycoprotein receptors and collagen. The adhesive activity of VWF depends on the size of its multimers, which range from 500 to over 10 000 kDa. There is good evidence that the high-molecular-weight multimers (HMWM), which are 5000-10 000 kDa, are the most effective in supporting interaction with collagen and platelet receptors and in facilitating wound healing under conditions of shear stress. Thus, these HMWM of VWF are of particular clinical interest. The unusually large multimers of VWF are, under normal conditions, cleaved by the plasma metalloproteinase ADAMTS13 to smaller, less adhesive multimers. A reduction or lack of HMWM, owing to a multimerization defect of VWF or to an increased susceptibility of VWF for ADAMTS13, leads to a functionally impaired VWF and the particular type 2A of von Willebrand disease. This review considers the biology and function of VWF multimers with a particular focus on the characterization of HMWM - their production, storage, release, degradation, and role in normal physiology. Evidence from basic research and the study of clinical diseases and their management highlight a pivotal role for the HMWM of VWF in hemostasis. |
| Databáze: | OpenAIRE |
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