Cellular stress induces erythrocyte assembly on intravascular von Willebrand factor strings and promotes microangiopathy

Journal article


Publication Details

Author(s): Nicolay JP, Thorn V, Daniel C, Amann KU, Siraskar B, Lang F, Hillgruber C, Goerge T, Hoffmann S, Gorzelanny C, Huck V, Mess C, Obser T, Schneppenheim R, Fleming I, Schneider MF, Schneider SW
Journal: Scientific Reports
Publication year: 2018
Volume: 8
Journal issue: 1
ISSN: 2045-2322


Abstract

Microangiopathy with subsequent organ damage represents a major complication in several diseases. The mechanisms leading to microvascular occlusion include von Willebrand factor (VWF), notably the formation of ultra-large von Willebrand factor fibers (ULVWFs) and platelet aggregation. To date, the contribution of erythrocytes to vascular occlusion is incompletely clarified. We investigated the platelet-independent interaction between stressed erythrocytes and ULVWFs and its consequences for microcirculation and organ function under dynamic conditions. In response to shear stress, erythrocytes interacted strongly with VWF to initiate the formation of ULVWF/erythrocyte aggregates via the binding of Annexin V to the VWF A1 domain. VWF-erythrocyte adhesion was attenuated by heparin and the VWF-specific protease ADAMTS13. In an in vivo model of renal ischemia/reperfusion injury, erythrocytes adhered to capillaries of wild-type but not VWF-deficient mice and later resulted in less renal damage. In vivo imaging in mice confirmed the adhesion of stressed erythrocytes to the vessel wall. Moreover, enhanced eryptosis rates and increased VWF binding were detected in blood samples from patients with chronic renal failure. Our study demonstrates that stressed erythrocytes have a pronounced binding affinity to ULVWFs. The discovered mechanisms suggest that erythrocytes are essential for the pathogenesis of microangiopathies and renal damage by actively binding to ULVWFs.


FAU Authors / FAU Editors

Amann, Kerstin Ute Prof. Dr.
Nephropathologische Abteilung im Pathologischen Institut
Daniel, Christoph Prof. Dr.
Nephropathologische Abteilung im Pathologischen Institut


External institutions with authors

Eberhard Karls Universität Tübingen
Goethe-Universität Frankfurt am Main
Ruprecht-Karls-Universität Heidelberg
Technische Universität Dortmund
Universitätsklinikum Hamburg-Eppendorf (UKE)
Universitätsklinikum Münster
Westfälische Wilhelms-Universität (WWU) Münster


How to cite

APA:
Nicolay, J.P., Thorn, V., Daniel, C., Amann, K.U., Siraskar, B., Lang, F.,... Schneider, S.W. (2018). Cellular stress induces erythrocyte assembly on intravascular von Willebrand factor strings and promotes microangiopathy. Scientific Reports, 8(1). https://dx.doi.org/10.1038/s41598-018-28961-2

MLA:
Nicolay, Jan P., et al. "Cellular stress induces erythrocyte assembly on intravascular von Willebrand factor strings and promotes microangiopathy." Scientific Reports 8.1 (2018).

BibTeX: 

Last updated on 2019-28-02 at 06:11