TY  - JOUR
A1  - Nicolay, Jan Peter
A1  - Thorn, Verena
A1  - Daniel, Christoph
A1  - Amann, Kerstin
A1  - Siraskar, Balasaheb
A1  - Lang, Florian
A1  - Hillgruber, Carina
A1  - Görge, Tobias
A1  - Hoffmann, Stefan
A1  - Gorzelanny, Christian
A1  - Huck, Volker
A1  - Mess, Christian
A1  - Obser, Tobias
A1  - Schneppenheim, Reinhard
A1  - Fleming, Ingrid
A1  - Schneider, Matthias F.
A1  - Schneider, Stefan W.
T1  - Cellular stress induces erythrocyte assembly on intravascular von Willebrand factor strings and promotes microangiopathy
T2  - Scientific reports
N2  - 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.
KW  - Experimental models of disease
KW  - Thrombosis
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47172
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-471729
SN  - 2045-2322
N1  - Rights and permissions: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 8
IS  - 1, Art. 10945
SP  - 1
EP  - 15
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -