Procarboxypeptidase U (proCPU, TAFI, proCPB2) in cerebrospinal fluid during ischemic stroke is associated with stroke progression, outcome and blood–brain barrier dysfunction

Autor: P.P. De Deyn, Margareta Ieven, Dorien Leenaerts, Dirk Hendriks, Anne-Marie Lambeir, Joachim C. Mertens, Raf Brouns, S. Engelborghs
Přispěvatelé: Neuroprotection & Neuromodulation, Clinical sciences, Neurology
Rok vydání: 2018
Předmět:
Male
Carboxypeptidase B2
Time Factors
stroke progression
procarvoxypeptidase U
030204 cardiovascular system & hematology
blood–brain barrier
Brain Ischemia
Brain ischemia
0302 clinical medicine
Cerebrospinal fluid
procarboxypeptidase U
Stroke
Medicine(all)
Aged
80 and over
Enzyme Precursors
dysfunction
Cerebral infarction
Hematology
Middle Aged
cerebral infarction
Prognosis
Up-Regulation
Chemistry
medicine.anatomical_structure
Blood-Brain Barrier
outcome
Disease Progression
Cardiology
Female
medicine.medical_specialty
Antifibrinolytic
medicine.drug_class
ProCPB2
Blood–brain barrier
cerebrospinal fluid
Capillary Permeability
03 medical and health sciences
Internal medicine
Journal Article
ischemic stroke
medicine
Humans
Biology
Aged
business.industry
Case-control study
medicine.disease
Case-Control Studies
Human medicine
business
Biomarkers
030217 neurology & neurosurgery
Zdroj: Journal of thrombosis and haemostasis
ISSN: 1538-7836
1538-7933
DOI: 10.1111/jth.13914
Popis: Essentials Little is known of procarboxypeptidase U (proCPU) in cerebrospinal fluid (CSF) of stroke patients. ProCPU levels were studied in CSF of controls and non-thrombolyzed acute ischemic stroke patients. ProCPU is elevated in CSF of stroke patients compared with controls. ProCPU in CSF correlates with stroke progression, outcome, and blood-brain barrier dysfunction. Summary: 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 (< 24 h 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 (i) stroke severity, (ii) stroke progression/recurrence, (iii) stroke outcome and (iv) 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 −1 vs. 3.50 (0.23) U L −1). Higher median [IQR] CSF/plasma proCPU ratios were found in patients with stroke progression ((6.0 [4.2–6.9]) × 10 −3) and poor outcome ((6.4 [3.9–7.0]) × 10 −3) after 3 months (modified Rankin Scale; mRS > 3) compared with patients without progression ((3.9 [2.7–5.4]) × 10 −3) or better outcome ((4.0 [2.8–5.0]) × 10 −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]) × 10 −3 vs. (3.7 [2.8–5.0]) × 10 −3). Conclusions ProCPU is increased in CSF during hyperacute ischemic stroke and is associated with stroke progression and outcome after 3 months, most likely due to BBB dysfunction in the hyperacute phase of ischemic stroke.
Databáze: OpenAIRE
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