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Von Willebrand factor is a major determinant of ADAMTS-13 decrease during mouse sepsis induced by cecum ligation and puncture

Abstract :

Summary. Background: During sepsis, von Willebrand factor (VWF) is abundantly secreted; the main mechanism regulating its size involves specific proteolysis by the metalloprotease ADAMTS-13. Objectives: To determine whether ADAMTS-13 consumption due to its binding to, and/or cleavage, of VWF contributes to its decrease during sepsis and whether abrogating or enhancing ADAMTS-13 activity influences sepsis outcome. Methods: ADAMTS-13 activity was evaluated in a model of sepsis induced by cecum ligature and puncture (CLP) in wild-type and Vwf−/− mice. Sepsis outcome was studied in those mice and in Adamts-13−/− mice. Finally, survival was studied in wild-type mice injected hydrodynamically with the human ADAMTS-13 gene. Results: In wild-type mice, CLP-induced sepsis elicited a significant ADAMTS-13 decrease, and a strong negative correlation existed between VWF and ADAMTS-13. In Vwf−/− mice, CLP also induced severe sepsis, but ADAMTS-13 was not significantly diminished. Notably, Vwf−/− mice lived significantly longer than wild-type mice. In contrast, Adamts-13−/− mice and wild-type mice were comparable with regard to thrombocytopenia, VWF concentrations, absence of thrombi, and survival. Hydrodynamic hADAMTS-13 gene transfer with the pLIVE expression vector resulted in high and stable ADAMTS13 activity in CLP mice; however, no impact on survival was observed. Conclusions: VWF secretion is a major determinant of ADAMTS-13 decrease in the CLP model, and plays an important role in sepsis-induced mortality, but the complete absence of its regulating protease, ADAMTS-13, had no detectable impact in this sepsis model. Furthermore, increasing ADAMTS-13 activity had no impact on survival.

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https://hal.univ-angers.fr/hal-03268560
Contributeur : Okina Université d'Angers <>
Soumis le : mercredi 23 juin 2021 - 12:11:35
Dernière modification le : mardi 13 juillet 2021 - 03:27:28

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Nicolas Lerolle, C. Dunois-Lardé, I. Badirou, D. Motto, Gary Hill, et al.. Von Willebrand factor is a major determinant of ADAMTS-13 decrease during mouse sepsis induced by cecum ligation and puncture. Journal of Thrombosis and Haemostasis, Wiley, 2009, 7 (5), pp.843 - 850. ⟨10.1111/j.1538-7836.2009.03313.x⟩. ⟨hal-03268560⟩

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