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Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
Soluble plasma-derived von Willebrand factor assembles to a haemostatically active filamentous network
Alexej Barg1, Rainer Ossig, Tobias Goerge
1Institute of Physiology II - Nanolab, University of Muenster, Muenster, Germany.
Thrombosis and Haemostasis
|March 30, 2007
Summary
Soluble von Willebrand factor (VWF) in plasma can self-assemble into fiber networks that bind platelets, mimicking unusually large VWF strings. These VWF fibers form under shear flow on collagen and are degraded by ADAMTS-13, contributing to vascular injury responses.
Area of Science:
- Biochemistry
- Hematology
- Cell Biology
Background:
- Von Willebrand factor (VWF) mediates platelet adhesion to injured blood vessels.
- Unusually large VWF (ULVWF) multimers form hyperactive strings that bind platelets.
Purpose of the Study:
- To investigate if soluble plasma-derived VWF can form thrombotically active multimers.
- To characterize the formation and function of VWF fibers from plasma VWF.
Main Methods:
- Isolation of soluble VWF multimers from human plasma.
- Immobilization on collagen matrix under shear flow.
- Atomic force microscopy (AFM) for nanostructure analysis.
- Assessment of platelet binding activity.
Main Results:
- Soluble VWF multimers self-assemble into fiber networks on collagen.
- VWF fiber formation is dependent on shear flow, VWF concentration, and binding surface.
- These VWF fibers are functionally active in binding platelets.
- ADAMTS-13 rapidly degrades the VWF fiber network.
- AFM revealed the nanostructure of self-associated filamentous VWF multimers.
Conclusions:
- Circulating VWF can form hyperactive VWF fibers on exposed subendothelial collagen during vascular injury.
- VWF fiber formation does not require cellular membrane ligands.
- These findings suggest a novel mechanism for VWF-mediated thrombosis.
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