Soluble plasma-derived von Willebrand factor assembles to a haemostatically active filamentous network

Alexej Barg; Rainer Ossig; Tobias Goerge; Matthias F. Schneider; Hermann Schillers; Hans Oberleithner; Stefan W. Schneider

doi:10.1160/TH06-05-0274

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(04): 514-526
DOI: 10.1160/TH06-05-0274

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Soluble plasma-derived von Willebrand factor assembles to a haemostatically active filamentous network

Alexej Barg

¹Institute of Physiology II – Nanolab

,

Rainer Ossig

²Institute of Physiological Chemistry and Pathobiochemistry

,

Tobias Goerge

³Department of Dermatology, University Hospital of Muenster, Muenster, Germany

⁴Currently: CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachussetts, USA

,

Matthias F. Schneider

⁵Biological Physics Group, University of Augsburg, Augsburg, Germany

,

Hermann Schillers

¹Institute of Physiology II – Nanolab

,

Hans Oberleithner

¹Institute of Physiology II – Nanolab

,

Stefan W. Schneider

³Department of Dermatology, University Hospital of Muenster, Muenster, Germany

› Author Affiliations

Abstract

Summary

The large glycoprotein vonWillebrand factor (VWF) is involved in the initial haemostatic reaction mediating the interaction between platelets and the injured vessel wall. It has been demonstrated that unusually large VWF (ULVWF) multimers after being released from endothelium are capable of developing elongated membrane-anchored strings that are hyperactive to bind platelets. In the present study we investigated whether soluble plasma-derived VWF is competent to develop similar thrombotically active multimers. We demonstrated that soluble VWF multimers isolated from human plasma self-assemble to a network of fibers immobilized on a collagen matrix and are functionally active to bind platelets. Formation of these VWF fibers depends on shear flow, concentration of solubleVWF, and a suitable binding surface. Self-assembly of soluble VWF does not require the presence of cellular membrane ligands. The network of fibers is subjected to rapid degradation by proteolytic activity of plasma ADAMTS-13.Atomic force microscopy images elucidate the nanostructure of VWF fibers and illustrate self-association and -aggregation of several filamentous multimers. Together, these results suggest that circulatingVWF can contribute to a formation of hyperactive VWF fibers on exposed subendothelial collagen during vascular injury.

Keywords

ULVWF multimers - platelet adhesion - atomic force microscopy - soluble VWF

Full Text

References

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