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

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 (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 8

Journal Issue: 1

DOI: 10.1038/s41598-018-28961-2

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.

Authors with CRIS profile

Christoph Daniel Department of Nephropathology Kerstin Ute Amann Department of Nephropathology

Involved external institutions

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

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).

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