Increased N‐terminal cleavage of alpha‐2‐antiplasmin in patients with liver cirrhosis

Summary Background The activity of alpha‐2‐antiplasmin (α2AP), the main fibrinolytic inhibitor, is modified by N‐ and C‐terminal proteolytic cleavages. C‐terminal cleavage converts plasminogen‐binding α2AP (PB‐α2AP) into a non‐plasminogen‐binding derivative. N‐terminal cleavage by antiplasmin‐cleavi...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2013-11, Vol.11 (11), p.2029-2036
Main Authors: Uitte de Willige, S., Malfliet, J. J. M. C., Janssen, H. L. A., Leebeek, F. W. G., Rijken, D. C.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
alpha-2-Antiplasmin - chemistry
alpha‐2‐antiplasmin
Antigens - chemistry
Case-Control Studies
case‐control study
Female
Fibrinolysis
fibrosis
Fibrosis - metabolism
Gelatinases - chemistry
Genotype
Humans
liver cirrhosis
Liver Cirrhosis - blood
Male
Membrane Proteins - chemistry
Middle Aged
Plasminogen - chemistry
Polymorphism, Single Nucleotide
Protein Binding
Protein Structure, Tertiary
Recombinant Proteins - chemistry
Serine Endopeptidases - chemistry
Solubility
Young Adult
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Summary:Summary Background The activity of alpha‐2‐antiplasmin (α2AP), the main fibrinolytic inhibitor, is modified by N‐ and C‐terminal proteolytic cleavages. C‐terminal cleavage converts plasminogen‐binding α2AP (PB‐α2AP) into a non‐plasminogen‐binding derivative. N‐terminal cleavage by antiplasmin‐cleaving enzyme (APCE), a soluble, circulating derivative of fibroblast activation protein (FAP), turns native Met‐α2AP into Asn‐α2AP, which is more quickly crosslinked into fibrin. Objectives We developed two novel enzyme‐linked immunosorbent assays (ELISAs) to determine the N‐terminal variation of α2AP to test the hypothesis that liver cirrhosis, characterized by increased expression of FAP/APCE, results in increased N‐terminal cleavage of α2AP. Patients/Methods α2AP and FAP/APCE antigen levels were measured in the plasma samples of 75 patients with cirrhosis with different severities and 30 healthy control individuals. The percentage of N‐terminal cleavage of α2AP was calculated. Results Compared with levels (median [interquartile range]) in control individuals, total PB‐α2AP levels and Met‐PB‐α2AP levels were reduced in cirrhosis patients (27.3 [21.4–41.3] μg mL−1 vs. 56.2 [49.6–62.8] μg mL−1, P 
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.12396