ADAMTS13 deficiency promotes microthrombosis in a murine model of diet-induced liver steatosis
Related Experiment Video
Updated: Mar 15, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
Lotte Geys, Dries Bauters, Elien Roose
1H. R. Lijnen, Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, CDG, Herestraat 49, Box 911, B-3000 Leuven, Belgium, Tel.: +32 16 372053, Fax: +32 16 345990,
Abstract:
ADAMTS13 cleaves ultralarge multimeric von Willebrand Factor (VWF), thereby preventing formation of platelet-rich microthrombi. ADAMTS13 is mainly produced by hepatic stellate cells, and numerous studies have suggested a functional role of ADAMTS13 in the pathogenesis of liver diseases. The aim of our study was to investigate a potential role of ADAMTS13 in formation of hepatic microthrombi and development of non-alcoholic steatohepatitis (NASH), and furthermore to evaluate whether plasmin can compensate for the absence of ADAMTS13 in removal of thrombi. Therefore, we used a model of high-fat diet-induced steatosis in Adamts13 deficient (Adamts13-/-) and wild-type (WT) control mice. Microthrombi were more abundant in the liver of obese Adamts13-/- as compared to obese WT or to lean Adamts13-/- mice. Obese Adamts13-/- mice displayed lower platelet counts and higher prevalence of ultra-large VWF multimers. Hepatic plasmin-α2-antiplasmin complex levels were comparable for obese WT and Adamts13-/- mice and were lower for lean Adamts13-/- than WT mice, not supporting marked activation of the fibrinolytic system. High fat diet feeding, as compared to normal chow, resulted in enhanced liver triglyceride levels for both genotypes (p < 0.0001) and steatosis (p < 0.0001 for WT mice, p = 0.002 for Adamts13-/- mice) without differences between the genotypes. Expression of markers of inflammation, oxidative stress, steatosis and fibrosis was affected by diet, but not by genotype. Thus, our data confirm that obesity promotes NASH, but do not support a detrimental role of ADAMTS13 in its development. However, Adamts13 deficiency in obese mice promotes hepatic microthrombosis, whereas a compensatory role of plasmin in removal of microthrombi in the absence of ADAMTS13 could not be demonstrated.
Insights
ADAMTS13 deficiency increases liver microthrombi in obese mice, suggesting it doesn't cause non-alcoholic steatohepatitis (NASH). Plasmin does not compensate for ADAMTS13's absence in thrombus removal.
Area of Science:
- Hematology
- Gastroenterology
- Pathology
Background:
- ADAMTS13 cleaves von Willebrand Factor (VWF), preventing microthrombi formation.
- ADAMTS13 is implicated in liver disease pathogenesis.
- Its role in non-alcoholic steatohepatitis (NASH) and hepatic microthrombosis is unclear.
Purpose of the Study:
- Investigate ADAMTS13's role in hepatic microthrombosis and NASH development.
- Evaluate plasmin's compensatory role in thrombus removal when ADAMTS13 is absent.
Main Methods:
- Used a high-fat diet-induced NASH model in Adamts13 deficient (Adamts13-/-) and wild-type (WT) mice.
- Assessed hepatic microthrombi, platelet counts, VWF multimer size, and plasmin-α2-antiplasmin complexes.
- Analyzed liver steatosis, inflammation, oxidative stress, and fibrosis markers.
Main Results:
- Obese Adamts13-/- mice had more hepatic microthrombi, lower platelet counts, and larger VWF multimers than obese WT mice.
- Diet, not genotype, influenced steatosis, inflammation, oxidative stress, and fibrosis.
- Plasmin-α2-antiplasmin levels did not indicate significant fibrinolytic system activation in Adamts13-/- mice.
Conclusions:
- Obesity promotes NASH, independent of ADAMTS13's detrimental role.
- ADAMTS13 deficiency exacerbates hepatic microthrombosis in obese mice.
- Plasmin does not compensate for ADAMTS13 in clearing hepatic microthrombi.
