Circulating soluble vascular adhesion protein 1 accounts fear the increased serum monoamine oxidase activity in chronic liver disease

Background & Aims: Vascular adhesion protein 1 (VAP-1) is an endothelial gl ycoprotein 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 p atients with liver diseases. Methods: sVAP-1 concentration and SSAO activit y were measured in peripheral, hepatic, and portal blood and in bile from p atients with liver disease and in peripheral blood of control subjects, usi ng 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 chron ic 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 massiv e 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 concentratio n 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 su bjects, patients with acute liver failure, and those with chronic liver dis ease (r = 0.895; P < 0.001). When: serum was depleted of sVAP-1 by immunoaf finity chromatography, SSAO activity was eliminated. Conclusions: sVAP-1 le vels are increased in chronic liver disease, and sVAP-1 is likely derived f rom the liver. Serum sVAP-1 displays SSAO activity and accounts for most of the monoamine oxidase activity in human serum.