Involvement of monocyte-derived extracellular vesicle-associated tissue factor activity in convallatoxin-induced hypercoagulability

• 資料種別: 博士論文
• タイトル: Involvement of monocyte-derived extracellular vesicle-associated tissue factor activity in convallatoxin-induced hypercoagulability
• 著者・編者: Morimoto, Mami; Tatsumi, Kohei; Takabayashi, Yoko; Sakata, Asuka; Yuui, Katsuya; Terazawa, Ikuko; Kudo, Risa; Kasuda, Shogo
• 著者標目: Morimoto, Mami; Tatsumi, Kohei; Takabayashi, Yoko; Sakata, Asuka; Yuui, Katsuya; Terazawa, Ikuko; Kudo, Risa; Kasuda, Shogo
• 出版事項: Lippincott, Williams & Wilkins
• 出版年月日等: 2023-04
• 出版年（W3CDTF）: 2023-04
• 並列タイトル等: 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
• タイトル（掲載誌）: Blood Coagulation & Fibrinolysis
• 巻号年月日等（掲載誌）: 34 3
• 掲載巻: 34
• 掲載号: 3
• 掲載ページ: 184-190
• ISSN（掲載誌）: ISSN : 0957-5235; ISSN : 1473-5733
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2023-06-23
• 報告番号: 甲第882号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: anticancer; cardiac glycoside; convallatoxin; monocyte; procoagulant; tissue factor
• 対象利用者: 一般
• 一般注記: 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
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1097/MBC.0000000000001211
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4204/10/01%e7%94%b2882%e6%9c%ac%e6%96%87.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4204/2/02%e7%94%b2882%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4204/3/03%e7%94%b2882%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext