J Thromb Haemost. 2021 Sep 30; doi: 10.1111/jth.15542. Epub 2021 Sep 30.
Tissue dynamics of von Willebrand factor characterized by a novel fluorescent protein-von Willebrand factor chimera.
Journal of thrombosis and haemostasis : JTH
Linru Xu, Yanyang Qiu, Yanqing Li, Yaxuan Wei, Yan Wan, Wei Deng
Affiliations
Affiliations
- Cyrus Tang Medical Institute and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China.
PMID: 34592034
DOI: 10.1111/jth.15542
Abstract
BACKGROUND: Tissue dynamics of von Willebrand factor (VWF) that are vital to its biological function have not been fully characterized.
OBJECTIVE: To develop a new fluorescent protein--VWF chimera (FP-VWF) that has similar hematologic function to wild-type VWF and use it to monitor the tissue dynamics of VWF distribution.
METHODS: Genotyping, platelet counting, tail bleeding time assay, agarose gels, western blot, platelet aggregation, proteolytic analysis, and ELISA were applied in characterizing the function of FP-VWF; fluorescence spectrometer and confocal fluorescence microscope were used to monitor the plasma and tissue distribution of FP-VWF.
RESULTS: The transgenic mice that carry the FP-VWF retain hematologic activity of VWF with plasma levels of FP-VWF reduced by 50% and there are reduced high molecular weight FP-VWF multimers compared to the wild-type mice. The GPIb-binding and ADAMTS-13 (A Disintegrin and Metalloprotease with ThrombSpondin type 1 motif, member 13) proteolytic efficiency of FP-VWF are similar to wild-type VWF. The tissue distribution of FP-VWF was probed directly through its intrinsic fluorescence at normal or stimulated status, which indicated that the medicine-stimulated endogenous FP-VWF seems primarily released from the aorta and cleared in the spleen. Similar results were observed in non-fluorescent mice through a standard immunofluorescence approach. The fluorescence signals of FP-VWF were also similar to the standard dye-based approach in detecting the FeCl
CONCLUSIONS: Together, these results suggest that this novel FP-VWF chimera is valuable in probing the tissue dynamics of VWF in quite a few biological and pharmaceutical applications.
© 2021 International Society on Thrombosis and Haemostasis.
Keywords: chimera; desmopressin; thrombosis; tissue distribution; von Willebrand factor
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