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Circulating dermatan sulfate and heparan sulfate/heparin proteoglycans in children undergoing liver transplantation
L Mitchell1, R Superina, M Delorme
1Department of Pediatrics, Children's Hospital, Chedoke-McMaster, Hamilton, Ontario, Canada.
Insights
In children undergoing liver transplantation, plasma levels of dermatan sulfate (DS) were elevated. This study identified DS and other glycosaminoglycans (GAGs) with anticoagulant activity in these patients.
Area of Science:
- Biochemistry
- Hepatology
- Proteoglycan Research
Background:
- The liver synthesizes dermatan sulfate (DS), heparan sulfate (HS), and heparin glycosaminoglycans (GAGs).
- Hepatic disease is associated with significantly increased tissue levels of DS GAGs.
Purpose of the Study:
- To investigate whether plasma levels of DS are elevated in children undergoing liver transplantation.
- To characterize the anticoagulant activity present in the plasma of these pediatric patients.
Main Methods:
- Plasma samples were collected from pediatric liver transplant recipients at various time points (preoperative, intraoperative, postoperative).
- Levels of DS, HS, and heparin anticoagulant activity were measured.
- Anticoagulant activity was purified using gel chromatography and reductive elimination to identify the molecular weight and nature of the active components.
Main Results:
- Fluctuating levels of DS, HS, and heparin anticoagulant activity were detected throughout the study period.
- Purified anticoagulant material had a mean molecular weight (Mr) of 110,000 D, reduced to 24,000 D after reductive elimination, indicating proteoglycan (PG) association.
- Further chromatography resolved two peaks of anticoagulant activity, suggesting the presence of at least two distinct PGs, one with DS GAG chains and others with HS and heparin GAG chains.
Conclusions:
- Plasma DS levels may increase in children following liver transplantation.
- The study identified proteoglycans with DS, HS, and heparin GAG chains exhibiting anticoagulant properties in pediatric liver transplant patients.
- These findings suggest a potential role for GAGs in the hemostatic changes observed post-liver transplantation.
Abstract:
The liver produces dermatan sulfate (DS), heparan sulfate (HS) and heparin glycosaminoglycans (GAG) and in the presence of hepatic disease, tissue levels of the DS GAG increase dramatically. We hypothesized that in children undergoing liver transplantation plasma levels of DS would be increased. Plasma from children undergoing liver transplantation were tested preoperative, intra operative and post operative at 24-48 h, and 1-3 weeks. Fluctuating levels of DS, HS and heparin anticoagulant activity were detected at all timepoints. The anticoagulant activity was purified and gel chromatography of the material displayed a mean Mr 110,000 D. Reductive elimination decreased the mean Mr 24,000 D indicating the activity resides on a proteoglycan (PG). The purified material was subjected to further chromatography and two peaks of anticoagulant activity resolved, compatible with at least two separate PGs, one with DS GAG chains and the additional PG(s) with HS and heparin GAG chains.