アクセス数 : ?
ダウンロード数 : ?
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
著者
松浦, 朋美 徳島大学大学院医科学教育部(医学専攻) 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Uematsu, Etsuko Tokushima University
Hara, Tomoya Shikoku Medical Center for Children and Adults
キーワード
atrial fibrillation
FXa
PAR2
inflammation
anticoagulants
資料タイプ
学位論文
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
ISSN
13469843
13474820
cat書誌ID
AA11591968
出版者
The Japanese Circulation Society
85
8
開始ページ
1383
終了ページ
1391
発行日
2021-07-21
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/
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
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3527号
学位記番号
甲医第1497号
学位授与年月日
2021-04-22
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系