Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis
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Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis. / Stockschlaeder, Marcus; Schneppenheim, Reinhard; Budde, Ulrich.
in: BLOOD COAGUL FIBRIN, Jahrgang 25, Nr. 3, 01.04.2014, S. 206-16.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis
AU - Stockschlaeder, Marcus
AU - Schneppenheim, Reinhard
AU - Budde, Ulrich
PY - 2014/4/1
Y1 - 2014/4/1
N2 - 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.
AB - 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.
KW - Animals
KW - Hemostasis
KW - Humans
KW - Platelet Adhesiveness
KW - von Willebrand Diseases
KW - von Willebrand Factor
U2 - 10.1097/MBC.0000000000000065
DO - 10.1097/MBC.0000000000000065
M3 - SCORING: Journal article
C2 - 24448155
VL - 25
SP - 206
EP - 216
JO - BLOOD COAGUL FIBRIN
JF - BLOOD COAGUL FIBRIN
SN - 0957-5235
IS - 3
ER -