Version 1
: Received: 30 January 2024 / Approved: 30 January 2024 / Online: 30 January 2024 (10:25:20 CET)
How to cite:
Hirao, H.; Kubota, T. Role of ADAMTS13, von Willebrand factor cleaving protease, in liver ischemia-reperfusion injury: Proposal of hepatic thrombotic microangiopathy. Preprints2024, 2024012103. https://doi.org/10.20944/preprints202401.2103.v1
Hirao, H.; Kubota, T. Role of ADAMTS13, von Willebrand factor cleaving protease, in liver ischemia-reperfusion injury: Proposal of hepatic thrombotic microangiopathy. Preprints 2024, 2024012103. https://doi.org/10.20944/preprints202401.2103.v1
Hirao, H.; Kubota, T. Role of ADAMTS13, von Willebrand factor cleaving protease, in liver ischemia-reperfusion injury: Proposal of hepatic thrombotic microangiopathy. Preprints2024, 2024012103. https://doi.org/10.20944/preprints202401.2103.v1
APA Style
Hirao, H., & Kubota, T. (2024). Role of ADAMTS13, von Willebrand factor cleaving protease, in liver ischemia-reperfusion injury: Proposal of hepatic thrombotic microangiopathy. Preprints. https://doi.org/10.20944/preprints202401.2103.v1
Chicago/Turabian Style
Hirao, H. and Toyonari Kubota. 2024 "Role of ADAMTS13, von Willebrand factor cleaving protease, in liver ischemia-reperfusion injury: Proposal of hepatic thrombotic microangiopathy" Preprints. https://doi.org/10.20944/preprints202401.2103.v1
Abstract
Although a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) serve as the cleaving protease of vWF-multimers, its role in liver ischemia-reperfusion injury (IRI), as well as partial liver transplantation (pLT), remains unknown. First, ADAMTS13 deficient mice were subjected to IRI to investigate the impact on hepatic IRI. Hepatic IRI significantly decreased serum ADAMTS13 activity, while simultaneously up-regulated intrahepatic vWF expression. Ablation of ADAMTS13 aggravated liver IRI by promoting platelet aggregation and disturbing microcirculation in the liv-er accompanied by exacerbated transaminase release and enhanced pro-inflammatory cytokine/chemokines levels. Adjunctive supplementation of recombinant ADAMTS13 (rADAMTS13) improved hepatic microcirculatory failure observed in ADAMTS13-null mice. Immunohistochemistry revealed massive platelet aggregation within hepatic micro-vasculatures in ADAMTS13-null mice, which was attenuated by rADAMTS13 treatment. Consequently, peripheral platelet counts, transaminase release, and pro-inflammatory cytokines/chemokines levels deteriorated in ADAMTS13-null mice, while ameliorated by rADAMTS13 administration. Notably, rADAMTS13 improved IRI-induced pathologies even in WT mice compared with those without. Next, we tested rADAMTS13 in the rat pLT model. Similarly, in rat pLT, ADAMTS13 supplementation attenuated the aforementioned pathologies observed in the experimental mouse model. In conclusion, ADAMTS13 plays a pivotal role in alleviating both hepatic microcirculation and inflammatory responses, thus providing a novel therapeutic approach against LT-related stress.
Keywords
ADAMTS13, von Willebrand factor; hepatic stellate cell; thrombocytopenia; liver transplantation
Subject
Medicine and Pharmacology, Transplantation
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
