Exploring the efficiency of thrombin inhibitors with a quantitative model of the coagulation cascade
© 2019 Federation of European Biochemical Societies..
A detailed mathematical description of the coagulation cascade is a challenging task due to a huge set of protein-protein interactions. Simplified models do not permit quantitative description of anticoagulants. The detailed mathematical model presented here was constructed with 98 reactions between 70 species. The model was verified using experimental data on thrombin generation. Four thrombin inhibitors, which have different inhibitory mechanisms, were incorporated into the model. All four thrombin inhibitors delayed prothrombin conversion into thrombin, but did not preclude it. At high inhibitor concentration, thrombin-mediated positive feedback loops were strongly inhibited and the proportion of prothrombin, converted with factor Xa only, was considerably increased. The most potent inhibitor of prothrombin conversion was aptamer NU172, which also binds prothrombin and inhibits its conversion.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:594 |
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| Enthalten in: |
FEBS letters - 594(2020), 6 vom: 24. März, Seite 995-1004 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zavyalova, Elena G [VerfasserIn] |
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| Links: |
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| Themen: |
Anticoagulant |
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| Anmerkungen: |
Date Completed 14.01.2021 Date Revised 14.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/1873-3468.13684 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM303392223 |
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| 520 | |a A detailed mathematical description of the coagulation cascade is a challenging task due to a huge set of protein-protein interactions. Simplified models do not permit quantitative description of anticoagulants. The detailed mathematical model presented here was constructed with 98 reactions between 70 species. The model was verified using experimental data on thrombin generation. Four thrombin inhibitors, which have different inhibitory mechanisms, were incorporated into the model. All four thrombin inhibitors delayed prothrombin conversion into thrombin, but did not preclude it. At high inhibitor concentration, thrombin-mediated positive feedback loops were strongly inhibited and the proportion of prothrombin, converted with factor Xa only, was considerably increased. The most potent inhibitor of prothrombin conversion was aptamer NU172, which also binds prothrombin and inhibits its conversion | ||
| 650 | 4 | |a Journal Article | |
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