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

Scientific Reports
Jan P NicolayStefan W Schneider

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 demonst...Continue Reading

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Citations

Jul 7, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Jenna R DiRitoGregory T Tietjen
Aug 17, 2019·Frontiers in Physiology·Virginia PretiniRichard Van Wijk
Sep 4, 2020·Journal of Thrombosis and Haemostasis : JTH·Francesco FerraroDaniel F Cutler
Apr 20, 2021·Frontiers in Pediatrics·Andrea H Gillespie, Allan Doctor
Jul 1, 2021·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Arief WibowoJanuar Wibawa Martha

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Methods Mentioned

BETA
light scattering
flow cytometry
ELISA
FACS
fluorescence microscopy

Software Mentioned

ZEN

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