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Temporal roles of platelet and coagulation pathways in collagen- and tissue factor-induced thrombus formation
Please always quote using this URN: urn:nbn:de:bvb:20-opus-284219
- In hemostasis and thrombosis, the complex process of thrombus formation involves different molecular pathways of platelet and coagulation activation. These pathways are considered as operating together at the same time, but this has not been investigated. The objective of our study was to elucidate the time-dependency of key pathways of thrombus and clot formation, initiated by collagen and tissue factor surfaces, where coagulation is triggered via the extrinsic route. Therefore, we adapted a microfluidics whole-blood assay with the MaastrichtIn hemostasis and thrombosis, the complex process of thrombus formation involves different molecular pathways of platelet and coagulation activation. These pathways are considered as operating together at the same time, but this has not been investigated. The objective of our study was to elucidate the time-dependency of key pathways of thrombus and clot formation, initiated by collagen and tissue factor surfaces, where coagulation is triggered via the extrinsic route. Therefore, we adapted a microfluidics whole-blood assay with the Maastricht flow chamber to acutely block molecular pathways by pharmacological intervention at desired time points. Application of the technique revealed crucial roles of glycoprotein VI (GPVI)-induced platelet signaling via Syk kinase as well as factor VIIa-induced thrombin generation, which were confined to the first minutes of thrombus buildup. A novel anti-GPVI Fab EMF-1 was used for this purpose. In addition, platelet activation with the protease-activating receptors 1/4 (PAR1/4) and integrin αIIbβ3 appeared to be prolongedly active and extended to later stages of thrombus and clot formation. This work thereby revealed a more persistent contribution of thrombin receptor-induced platelet activation than of collagen receptor-induced platelet activation to the thrombotic process.…
Author: | Stefano Navarro, David Stegner, Bernhard Nieswandt, Johan W. M. Heemskerk, Marijke J. E. Kuijpers |
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URN: | urn:nbn:de:bvb:20-opus-284219 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Medizinische Fakultät / Institut für Experimentelle Biomedizin | |
Language: | English |
Parent Title (English): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Year of Completion: | 2021 |
Volume: | 23 |
Issue: | 1 |
Article Number: | 358 |
Source: | International Journal of Molecular Sciences (2022) 23:1, 358. https://doi.org/10.3390/ijms23010358 |
DOI: | https://doi.org/10.3390/ijms23010358 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | coagulation; fibrin; glycoprotein VI; platelet receptors; spatiotemporal thrombus; thrombin |
Release Date: | 2023/07/12 |
Date of first Publication: | 2021/12/29 |
EU-Project number / Contract (GA) number: | 766118 |
OpenAIRE: | OpenAIRE |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |