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

• Verfasst von: Nicolay, Jan Peter [VerfasserIn]
• Verfasst von: Thorn, Verena [VerfasserIn]
• Verfasst von: Gorzelanny, Christian [VerfasserIn]
• Verfasst von: Huck, Volker [VerfasserIn]
• Titel: Cellular stress induces erythrocyte assembly on intravascular von Willebrand factor strings and promotes microangiopathy
• Verf.angabe: Jan P. Nicolay, Verena Thorn, Christoph Daniel, Kerstin Amann, Balasaheb Siraskar, Florian Lang, Carina Hillgruber, Tobias Goerge, Stefan Hoffmann, Christian Gorzelanny, Volker Huck, Christian Mess, Tobias Obser, Reinhard Schneppenheim, Ingrid Fleming, Matthias F. Schneider and Stefan W. Schneider
• E-Jahr: 2018
• Jahr: 19 July 2018
• Umfang: 15 S.
• Fussnoten: Gesehen am 24.11.2020
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Springer Nature, 2011
• Jahr Quelle: 2018
• Band/Heft Quelle: 8(2018) Artikel-Nummer 10945, 15 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-018-28961-2
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1740868420

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.