Publication
Title
Procarboxypeptidase U (proCPU, TAFI, proCPB2) in cerebrospinal fluid during ischemic stroke is associated with stroke progression, outcome and blood-brain barrier dysfunction
Author
Abstract
Background Procarboxypeptidase U (proCPU, TAFI, proCPB2), the zymogen of CPU which is a potent antifibrinolytic enzyme and a modulator of inflammation has previously been investigated in plasma of stroke patients, but so far, no information on the proCPU levels in cerebrospinal fluid (CSF) during acute ischemic stroke (AIS) is available. Objectives This case-control observational study investigates proCPU in CSF of AIS patients compared with controls with an intact blood-brain barrier (BBB) and evaluates the relationship of CSF/plasma proCPU ratios with stroke parameters. Methods A sensitive HPLC-based enzymatic assay was used to determine proCPU levels in CSF of non-thrombolyzed patients in the hyperacute phase (<24h after onset) of AIS (n=72). Individuals (n=32) without stroke, an intact BBB and no apparent abnormalities in biochemical and microbiological tests, served as controls. Relations between the CSF/plasma proCPU ratio and (a) stroke severity, (b) stroke progression/recurrence, (c) stroke outcome and (d) BBB dysfunction (CSF/serum albumin ratio) were assessed. Results Mean (SEM) proCPU levels were elevated in the CSF of stroke patients compared with controls (4.36 (0.23) U/L vs. 3.50 (0.23) U/L). Higher median [IQR] CSF/plasma proCPU ratios were found in patients with stroke progression ((6.0 [4.2-6.9])x10-3) and poor outcome ((6.4 [3.9-7.0])x10-3) after 3 months (mRS>3) compared with patients with no progression ((3.9 [2.7-5.4])x10-3) or better outcome ((4.0 [2.8-5.0])x10-3). In stroke patients with a disrupted BBB, proCPU ratios were higher compared with stroke patients with an intact BBB (6.4 [5.8-9.0])x10-3 vs. (3.7 [2.8-5.0])x10-3). Conclusions ProCPU is increased in CSF during hyperacute ischemic stroke and are associated with stroke progression and outcome after 3 months, most likely due to BBB dysfunction in the hyperacute phase of ischemic stroke.
Language
English
Source (journal)
Journal of thrombosis and haemostasis. - Oxford
Publication
Oxford : 2018
ISSN
1538-7933
DOI
10.1111/JTH.13914
Volume/pages
16 :2 (2018) , p. 342-348
ISI
000424909700017
Pubmed ID
29194929
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Carboxypeptidase U - a new drug target for the improvement of treatment in acute ischemic stroke.
The role of carboxypeptidase U in atherosclerosis and its thrombotic complications.
An integrated approach to the unraveling of the pathogenesis of CNS and PNS neurodegenerative disorders.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 07.12.2017
Last edited 09.10.2023
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