Circulating soluble vascular adhesion protein 1 accounts for the increased serum monoamine oxidase activity in chronic liver disease.
OBJECTIVE
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) x 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) x 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.
Kurkijärvi
R
R
MediCity Research Laboratories, University of Turku and National Public Health Institute Department in Turku, Turku, Finland.
Yegutkin
G G
GG
Gunson
B K
BK
Jalkanen
S
S
Salmi
M
M
Adams
D H
DH
D006631:Amine Oxidase (Copper-Containing) / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000201:enzymology; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood*; D002908:Chronic Disease; D015179:Colorectal Neoplasms / Q000097:blood; D003404:Creatinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006505:Hepatitis / Q000097:blood* / Q000145:classification; D006519:Hepatitis, Alcoholic / Q000097:blood; D006801:Humans; D008102:Liver Circulation; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood; D008107:Liver Diseases / Q000097:blood* / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood; D016031:Liver Transplantation; D008995:Monoamine Oxidase / Q000097:blood*; D011168:Portal System; D012016:Reference Values; D012795:Sialoglycoproteins / Q000097:blood
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D012795:Sialoglycoproteins; D003404:Creatinine; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D001219:Aspartate Aminotransferases; D001663:Bilirubin