Alternative Titleコンバラトキシンによる凝固亢進における単球由来組織因子陽性細胞外小胞の関与
Note (General)type:Thesis
Objectives:Convallatoxin (CNT) is a natural cardiac glycoside extracted from lily of the valley (Convallaria majalis). Although it is empirically known to cause blood coagulation disorders, the underlying mechanism remains unclear. CNT exerts cytotoxicity and increases tissue factor (TF) expression in endothelial cells. However, the direct action of CNT on blood coagulation remains unclear. Therefore, herein, we investigated the effects of CNT on whole blood coagulation system and TF expression in monocytes.Methods:Blood samples were collected from healthy volunteers to measure plasma thrombin–antithrombin complex (TAT) concentration using ELISA and to perform rotational thromboelastometry (ROTEM) and whole-blood extracellular vesicle (EV)-associated TF (EV-TF) analysis. The effects of CNT were also investigated using the monocytic human cell line THP-1. Quantitative real-time PCR and western blotting were performed, and PD98059, a mitogen-activated protein kinase (MAPK) inhibitor, was used to elucidate the action mechanism of CNT-mediated TF production.Results:CNT treatment increased EV-TF activity, shortened the whole blood clotting time in rotational thromboelastometry analysis, and increased TAT levels, which is an index of thrombin generation. Furthermore, CNT increased TF mRNA expression in THP-1 cells and EV-TF activity in the cell culture supernatant. Therefore, CNT may induce a hypercoagulable state with thrombin generation, in which elevated EV-TF activity derived from monocytes might be involved. These procoagulant effects of CNT were reversed by PD98059, suggesting that CNT-induced TF production in monocytes might be mediated by the MAPK pathway.Conclusions:The findings of the present study have further clarified the procoagulant properties of CNT.
権利情報：© 2023 Wolters Kluwer Health, Inc. All rights reserved. This is a non-final version of an article published in final form in [Morimoto, Mami et al. Involvement of monocyte-derived extracellular vesicle-associated tissue factor activity in convallatoxin-induced hypercoagulability. Blood Coagulation & Fibrinolysis. April 2023 - Volume 34 - Issue 3 - p 184-190, doi: http://dx.doi.org/10.1097/MBC.0000000000001211].
identifier:Blood Coagulation & Fibrinolysis. 2023 Apr, vol.34, no.3, p184-190
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4204
identifier:Blood Coagulation & Fibrinolysis, 34(3): 184-190
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2024-11-12T17:29:46+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション