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Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets

Platelet-stored activated blood coagulation factor X (FXa) has great potential in the gene therapy of hemophilia B (HB). However, we still need to understand more about the properties of FXa-storing platelets and how dietary factors affect them. We created transgenic mice called 2bFXa-HB, which had...

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Autores principales: Han, Wenwen, Huang, Rui, Li, Binbin, Liu, Lu, Xu, Wenjue, Zhang, Guowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543635/
https://www.ncbi.nlm.nih.gov/pubmed/37779119
http://dx.doi.org/10.1038/s41598-023-43649-y
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author Han, Wenwen
Huang, Rui
Li, Binbin
Liu, Lu
Xu, Wenjue
Zhang, Guowei
author_facet Han, Wenwen
Huang, Rui
Li, Binbin
Liu, Lu
Xu, Wenjue
Zhang, Guowei
author_sort Han, Wenwen
collection PubMed
description Platelet-stored activated blood coagulation factor X (FXa) has great potential in the gene therapy of hemophilia B (HB). However, we still need to understand more about the properties of FXa-storing platelets and how dietary factors affect them. We created transgenic mice called 2bFXa-HB, which had stable expression and storage of FXa in their platelets, resulting in the alleviation of the bleeding disorder in these mice. Even after inducing anti-factor IX (FIX) inhibitors in 2bFXa-HB mice, the hemorrhage phenotype could still be rescued by the expression of FXa. The activation capacity of 2bFXa-HB platelets remained unchanged, and there were no signs of elevated thrombotic risk in these mice. In an acute alcohol exposure mouse model, a single administration of alcohol reduced both the number of platelets and their activation capacity, as well as impaired coagulation function. However, it did not increase the markers of thrombotic risk in either 2bFXa-HB or HB mice. These results suggest that FXa storage in platelets is safe and effective for treatment of HB, but alcohol could impair the therapeutic effect of FXa-containing platelets.
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spelling pubmed-105436352023-10-03 Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets Han, Wenwen Huang, Rui Li, Binbin Liu, Lu Xu, Wenjue Zhang, Guowei Sci Rep Article Platelet-stored activated blood coagulation factor X (FXa) has great potential in the gene therapy of hemophilia B (HB). However, we still need to understand more about the properties of FXa-storing platelets and how dietary factors affect them. We created transgenic mice called 2bFXa-HB, which had stable expression and storage of FXa in their platelets, resulting in the alleviation of the bleeding disorder in these mice. Even after inducing anti-factor IX (FIX) inhibitors in 2bFXa-HB mice, the hemorrhage phenotype could still be rescued by the expression of FXa. The activation capacity of 2bFXa-HB platelets remained unchanged, and there were no signs of elevated thrombotic risk in these mice. In an acute alcohol exposure mouse model, a single administration of alcohol reduced both the number of platelets and their activation capacity, as well as impaired coagulation function. However, it did not increase the markers of thrombotic risk in either 2bFXa-HB or HB mice. These results suggest that FXa storage in platelets is safe and effective for treatment of HB, but alcohol could impair the therapeutic effect of FXa-containing platelets. Nature Publishing Group UK 2023-10-01 /pmc/articles/PMC10543635/ /pubmed/37779119 http://dx.doi.org/10.1038/s41598-023-43649-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Han, Wenwen
Huang, Rui
Li, Binbin
Liu, Lu
Xu, Wenjue
Zhang, Guowei
Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets
title Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets
title_full Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets
title_fullStr Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets
title_full_unstemmed Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets
title_short Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets
title_sort characteristics of fxa-storing platelets in hemophilia b mice and the influence of alcohol on the platelets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543635/
https://www.ncbi.nlm.nih.gov/pubmed/37779119
http://dx.doi.org/10.1038/s41598-023-43649-y
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