Gastroenterology

Gastroenterology

Volume 119, Issue 4, October 2000, Pages 1096-1103
Gastroenterology

Liver, Pancreas, and Biliary Tract
Circulating soluble vascular adhesion protein 1 accounts for the increased serum monoamine oxidase activity in chronic liver disease,☆☆

https://doi.org/10.1053/gast.2000.18163Get rights and content

Abstract

Background & Aims: Vascular adhesion protein 1 (VAP-1) is an endothelial glycoprotein that supports adhesion of lymphocytes to hepatic endothelium and has sequence homology with semicarbazide-sensitive amine oxidases (SSAOs). We investigated whether soluble VAP-1 (sVAP-1) displays SSAO activity and thereby accounts for increased monoamine oxidase activity in the serum of patients with liver diseases. Methods: sVAP-1 concentration and SSAO activity were measured in peripheral, hepatic, and portal blood and in bile from patients with liver disease and in peripheral blood of control subjects, using enzyme-linked immunosorbent assay and enzymatic assays. Results: sVAP-1 concentration (mean [±SE], 143.67 [34.97–92.67] ng/mL) and SSAO activity (18.8 [12.0–24.6] nmol · mL−1 · h−1) were significantly increased in chronic liver diseases compared with healthy controls (87.1 [53.5–127] ng/mL [P < 0.001] and 10.7 [6.5–12.7] nmol · mL−1 · h−1 [P < 0.05]) but not in massive necrosis caused by paracetamol poisoning (109 [80.3–140] ng/mL and 8.9 [5.7–12.3] nmol · mL−1 · h−1). sVAP-1 correlated with serum transaminase and bilirubin but not with creatinine. In 5 paired samples, sVAP-1 concentration was higher in hepatic (median, 113 [range, 53–122]) than in portal vein (102 [42–109]; 2P <0.05), and was not detected in bile. There was a highly significant correlation between serum sVAP-1 and SSAO activity in normal subjects, patients with acute liver failure, and those with chronic liver disease (r = 0.895; P < 0.001). When serum was depleted of sVAP-1 by immunoaffinity chromatography, SSAO activity was eliminated. Conclusions: sVAP-1 levels are increased in chronic liver disease, and sVAP-1 is likely derived from the liver. Serum sVAP-1 displays SSAO activity and accounts for most of the monoamine oxidase activity in human serum.

GASTROENTEROLOGY 2000;119:1096-1103

Section snippets

Patients

Serum samples were collected and frozen at −70°C until analysis. All diagnoses were made based on standard clinical, biochemical, and histologic criteria. Patients with autoimmune hepatitis were maintained on corticosteroid and/or azathioprine treatment; posttransplant patients were stable on combination therapy (azathioprine and cyclosporine or tacrolimus) with normal or near-normal liver biochemistry. Patients with chronic liver disease were not being treated with immunosuppressive therapy.

sVAP-1 levels are increased in liver disease

VAP-1 levels in healthy controls varied from 53.5 to 127 ng/mL with a median of 87.1 ng/mL. These results are similar to the normal range we have reported for sVAP-1 (49–138 ng/mL).22 Compared with the healthy control population, sVAP-1 levels were increased in many types of chronic liver disease (Figure 1): alcoholic cirrhosis, alcoholic hepatitis, cryptogenic cirrhosis, PBC (P < 0.01 for each group vs. healthy controls), and viral hepatitis (P < 0.05 vs. controls).

. SVAP-1 level is increased in

Discussion

We report increased serum levels of VAP-1 in chronic liver disease but normal levels in acute fulminant hepatic failure. We also show that sVAP-1 levels correlate with serum transaminase levels in chronic disease and that it is not excreted in bile. Perhaps most interestingly, we show that sVAP-1 is responsible for the SSAO activity in the serum of patients with liver disease and provide a molecular explanation for this long-standing observation.24, 31, 32, 33

We had previously shown that sVAP-1

Acknowledgements

The authors thank Stefan Hubscher for histologic analysis, and Drs. Neil Fisher, Damian Dowling, and Simon Ollif and other colleagues in the Liver Unit for sample collection.

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    Supported by grants from the Wellcome Trust, The European Commission, the Finnish Academy, Technology Development Center of Finland, the Sigrid Juselius Foundation, and the Finnish Cultural Foundation and Paulo Foundation.

    ☆☆

    Address requests for reprints to: David Adams, M.D., Liver Research Laboratories, University of Birmingham, Institute for Clinical Science, Queen Elizabeth Hospital, Edgbaston, Birmingham, England. e-mail: [email protected]; fax: (44) 121-627-4297.

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