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Model‐dependent contributions of FXII and FXI to venous thrombosis in mice
BACKGROUND: The intrinsic pathway factors (F) XII and FXI have been shown to contribute to thrombosis in animal models. We assessed the role of FXII and FXI in venous thrombosis in three distinct mouse models. METHODS: Venous thrombosis was assessed in mice genetically deficient for either FXII or F...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693194/ https://www.ncbi.nlm.nih.gov/pubmed/33094904 http://dx.doi.org/10.1111/jth.15037 |
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author | Grover, Steven P. Olson, Tatianna M. Cooley, Brian C. Mackman, Nigel |
author_facet | Grover, Steven P. Olson, Tatianna M. Cooley, Brian C. Mackman, Nigel |
author_sort | Grover, Steven P. |
collection | PubMed |
description | BACKGROUND: The intrinsic pathway factors (F) XII and FXI have been shown to contribute to thrombosis in animal models. We assessed the role of FXII and FXI in venous thrombosis in three distinct mouse models. METHODS: Venous thrombosis was assessed in mice genetically deficient for either FXII or FXI. Three models were used: the inferior vena cava (IVC) stasis, IVC stenosis, and femoral vein electrolytic injury models. RESULTS: In the IVC stasis model, FXII and FXI deficiency did not affect the size of thrombi but their absence was associated with decreased levels of fibrin(ogen) and an increased level of the neutrophil extracellular trap marker citrullinated histone H3. In contrast, a deficiency of either FXII or FXI resulted in a significant and equivalent reduction in thrombus weight and incidence of thrombus formation in the IVC stenosis model. Thrombi formed in the IVC stenosis model contained significantly higher levels of citrullinated histone H3 compared with the thrombi formed in the IVC stasis model. Deletion of either FXII or FXI also resulted in a significant and equivalent reduction in both fibrin and platelet accumulation in the femoral vein electrolytic injury model. CONCLUSIONS: Collectively, these data indicate that FXII and FXI contribute to the size of venous thrombosis in models with blood flow and thrombus composition in a stasis model. This study also demonstrates the importance of using multiple mouse models to assess the role of a given protein in venous thrombosis. |
format | Online Article Text |
id | pubmed-7693194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76931942020-12-11 Model‐dependent contributions of FXII and FXI to venous thrombosis in mice Grover, Steven P. Olson, Tatianna M. Cooley, Brian C. Mackman, Nigel J Thromb Haemost THROMBOSIS BACKGROUND: The intrinsic pathway factors (F) XII and FXI have been shown to contribute to thrombosis in animal models. We assessed the role of FXII and FXI in venous thrombosis in three distinct mouse models. METHODS: Venous thrombosis was assessed in mice genetically deficient for either FXII or FXI. Three models were used: the inferior vena cava (IVC) stasis, IVC stenosis, and femoral vein electrolytic injury models. RESULTS: In the IVC stasis model, FXII and FXI deficiency did not affect the size of thrombi but their absence was associated with decreased levels of fibrin(ogen) and an increased level of the neutrophil extracellular trap marker citrullinated histone H3. In contrast, a deficiency of either FXII or FXI resulted in a significant and equivalent reduction in thrombus weight and incidence of thrombus formation in the IVC stenosis model. Thrombi formed in the IVC stenosis model contained significantly higher levels of citrullinated histone H3 compared with the thrombi formed in the IVC stasis model. Deletion of either FXII or FXI also resulted in a significant and equivalent reduction in both fibrin and platelet accumulation in the femoral vein electrolytic injury model. CONCLUSIONS: Collectively, these data indicate that FXII and FXI contribute to the size of venous thrombosis in models with blood flow and thrombus composition in a stasis model. This study also demonstrates the importance of using multiple mouse models to assess the role of a given protein in venous thrombosis. John Wiley and Sons Inc. 2020-08-28 2020-11 /pmc/articles/PMC7693194/ /pubmed/33094904 http://dx.doi.org/10.1111/jth.15037 Text en © 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | THROMBOSIS Grover, Steven P. Olson, Tatianna M. Cooley, Brian C. Mackman, Nigel Model‐dependent contributions of FXII and FXI to venous thrombosis in mice |
title | Model‐dependent contributions of FXII and FXI to venous thrombosis in mice |
title_full | Model‐dependent contributions of FXII and FXI to venous thrombosis in mice |
title_fullStr | Model‐dependent contributions of FXII and FXI to venous thrombosis in mice |
title_full_unstemmed | Model‐dependent contributions of FXII and FXI to venous thrombosis in mice |
title_short | Model‐dependent contributions of FXII and FXI to venous thrombosis in mice |
title_sort | model‐dependent contributions of fxii and fxi to venous thrombosis in mice |
topic | THROMBOSIS |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693194/ https://www.ncbi.nlm.nih.gov/pubmed/33094904 http://dx.doi.org/10.1111/jth.15037 |
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