Activated Factor X Signaling Pathway via Protease-Activated Receptor 2 is a Novel Therapeutic Target for Preventing Atrial Fibrillation

• Material Type: 博士論文
• Title: Activated Factor X Signaling Pathway via Protease-Activated Receptor 2 is a Novel Therapeutic Target for Preventing Atrial Fibrillation
• Author/Editor: Matsuura, Tomomi; Soeki, Takeshi; Fukuda, Daiju; Uematsu, Etsuko; Tobiume, Takeshi; Hara, Tomoya; Kusunose, Kenya; Ise, Takayuki; Yamaguchi, Koji; Yagi, Shusuke; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Sata, Masataka
• Author Heading: Matsuura, Tomomi; Soeki, Takeshi; Fukuda, Daiju; Uematsu, Etsuko; Tobiume, Takeshi; Hara, Tomoya; Kusunose, Kenya; Ise, Takayuki; Yamaguchi, Koji; Yagi, Shusuke; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Sata, Masataka
• Publication, Distribution, etc.: The Japanese Circulation Society
• Publication Date: 2021-07-21
• Publication Date (W3CDTF): 2021-07-21
• Alternative Title: 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
• Periodical title: Circulation Journal
• No. or year of volume/issue: 85 8
• Volume: 85
• Issue: 8
• Pages: 1383-1391
• ISSN (Periodical Title): ISSN : 1346-9843; ISSN : 1347-4820
• Degree grantor/type: 徳島大学
• Date Granted: 2021-04-22
• Dissertation Number: 甲第3527号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: atrial fibrillation; FXa; PAR2; inflammation; anticoagulants
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license. https://creativecommons.org/licenses/by-nc-nd/4.0/
• Related Material (DOI): 10.1253/circj.CJ-20-1006
• Data Provider (Database): 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
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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