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Assaying ADAMTS13 Activity as a Potential Prognostic Biomarker for Sinusoidal Obstruction Syndrome in Mice
Masakazu Saeki1,2, Seiichi Munesue2, Yuri Higashi1,2
1Department of Gastroenterological Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
International Journal of Molecular Sciences
|November 25, 2023
Summary
Sinusoidal obstruction syndrome (SOS) is a severe liver condition. ADAMTS13 activity decrease and VWF-A2 increase indicate potential biomarkers for early SOS detection and treatment.
Area of Science:
- Hepatology
- Hematology
- Transplantation Medicine
Background:
- Sinusoidal obstruction syndrome (SOS) is a critical liver complication following transplantation or chemotherapy.
- Early detection and treatment are vital for patient survival due to the risk of liver failure.
Purpose of the Study:
- To investigate the role of ADAMTS13 (a disintegrin-like metalloproteinase with thrombospondin type 1 motifs 13) in SOS development.
- To identify potential biomarkers for early SOS diagnosis and therapeutic intervention.
Main Methods:
- An SOS mouse model was induced using monocrotaline (MCT).
- Mice were analyzed at various time points post-MCT administration.
- Blood and liver samples were collected for histopathology and biochemical assays, including platelet aggregation, VWF, and ADAMTS13 activity.
Main Results:
- SOS was evident in livers 12 hours after MCT injection.
- Platelet aggregation and VWF signals were observed in the liver sinusoids.
- ADAMTS13 plasma concentration peaked early, but its enzyme activity significantly decreased over 48 hours.
- VWF-A2 domain concentrations increased inversely with ADAMTS13 activity.
Conclusions:
- Decreased ADAMTS13 activity and increased VWF-A2 domain concentrations correlate with SOS progression.
- Plasma levels and activity of ADAMTS13 show promise as early diagnostic and therapeutic biomarkers for SOS.
