Carboxypeptidase U (TAFIa) Is Rapidly Activated and Deactivated Following Thrombolysis and Thrombectomy in Stroke Patients.
Carboxypeptidase B2
Clinical trial
Fibrinolysis
Ischemic stroke
Thrombin-activatable fibrinolysis inhibitor
Journal
Translational stroke research
ISSN: 1868-601X
Titre abrégé: Transl Stroke Res
Pays: United States
ID NLM: 101517297
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
25
06
2021
accepted:
27
10
2021
revised:
19
10
2021
pubmed:
20
11
2021
medline:
1
11
2022
entrez:
19
11
2021
Statut:
ppublish
Résumé
The antifibrinolytic enzyme carboxypeptidase U (CPU, TAFIa, CPB2) is an appealing target for the treatment of acute ischemic stroke (AIS). Increased insights in CPU activation and inactivation during thrombolysis (rtPA) with or without endovascular thrombectomy (EVT) are required to develop CPU inhibitors as profibrinolytic agents with optimal benefits/risks. Therefore, CPU kinetics during ischemic stroke treatment were evaluated. AIS patients with documented cerebral artery occlusion receiving rtPA (N = 20) or rtPA + EVT (N = 16) were included. CPU activation during thrombolysis was measured by an ultrasensitive HPLC-based CPU activity method and by an ELISA measuring both CPU and inactivated CPU (CPU + CPUi). Intravenous blood samples were collected at admission and throughout the first 24 h. Additional in situ blood samples were collected in the rtPA + EVT cohort proximal from the thrombus. The NIHSS score was determined at baseline and 24 h. CPU activity and CPU + CPUi levels increased upon rtPA administration and reached peak values at the end of thrombolysis (1 h). High inter-individual variability was observed in both groups. CPU activity decreased rapidly within 3 h, while CPU + CPUi levels were still elevated at 7 h. CPU activity or CPU + CPUi levels were similar in in situ and peripheral samples. No correlation between CPU or CPU + CPUi and NIHSS or thrombus localization was found. The CPU system was rapidly activated and deactivated following thrombolysis and thrombectomy in stroke patients, suggesting that a CPU inhibitor would have to be administered during rtPA infusion and over the next few hours. The high CPU generation variability suggests that some patients may not respond to the treatment. EudraCT number 2017-002760-41.
Identifiants
pubmed: 34796454
doi: 10.1007/s12975-021-00962-w
pii: 10.1007/s12975-021-00962-w
doi:
Substances chimiques
Carboxypeptidase B2
EC 3.4.17.20
Tissue Plasminogen Activator
EC 3.4.21.68
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
959-969Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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