ID | 116065 |
タイトル別表記 | プロテアーゼ活性化型受容体2を介した活性化凝固第X因子シグナル経路は心房細動予防のための新しい治療標的である
Role of Protease-Activated Receptor 2 in AF
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著者 |
Uematsu, Etsuko
Tokushima University
Hara, Tomoya
Shikoku Medical Center for Children and Adults
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キーワード | atrial fibrillation
FXa
PAR2
inflammation
anticoagulants
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資料タイプ |
学位論文
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抄録 | Background: Activated factor X (FXa), which contributes to chronic inflammation via protease-activated receptor 2 (PAR2), might play an important role in atrial fibrillation (AF) arrhythmogenesis. This study aimed to assess whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban ameliorates atrial inflammation and prevents AF.
Methods and Results: In Study 1, PAR2 deficient (PAR2−/−) and wild-type mice were infused with angiotensin II (Ang II) or a vehicle via an osmotic minipump for 2 weeks. In Study 2, spontaneously hypertensive rats (SHRs) were treated with rivaroxaban, warfarin, or vehicle for 2 weeks after 8h of right atrial rapid pacing. The AF inducibility and atrial remodeling in both studies were examined. Ang II-treated PAR2−/− mice had a lower incidence of AF and less mRNA expression of collagen1 and collagen3 in the atrium compared to wild-type mice treated with Ang II. Rivaroxaban significantly reduced AF inducibility compared with warfarin or vehicle. In SHRs treated with a vehicle, rapid atrial pacing promoted gene expression of inflammatory and fibrosis-related biomarkers in the atrium. Rivaroxaban, but not warfarin, significantly reduced expression levels of these genes. Conclusions: The FXa–PAR2 signaling pathway might contribute to AF arrhythmogenesis associated with atrial inflammation. A direct FXa inhibitor, rivaroxaban, could prevent atrial inflammation and reduce AF inducibility, probably by inhibiting the pro-inflammatory activation. |
掲載誌名 |
Circulation Journal
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ISSN | 13469843
13474820
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cat書誌ID | AA11591968
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出版者 | The Japanese Circulation Society
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巻 | 85
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号 | 8
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開始ページ | 1383
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終了ページ | 1391
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発行日 | 2021-07-21
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備考 | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Tomomi Matsuuraの学位論文として提出され,学位審査・授与の対象となっている。 |
権利情報 | This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license. https://creativecommons.org/licenses/by-nc-nd/4.0/
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第3527号
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学位記番号 | 甲医第1497号
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学位授与年月日 | 2021-04-22
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学位名 |
博士(医学)
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学位授与機関 |
徳島大学
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部局 |
病院
医学系
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