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ID 116065
Title Alternative
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
Author
Uematsu, Etsuko Tokushima University
Hara, Tomoya Shikoku Medical Center for Children and Adults
Keywords
atrial fibrillation
FXa
PAR2
inflammation
anticoagulants
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Circulation Journal
ISSN
13469843
13474820
NCID
AA11591968
Publisher
The Japanese Circulation Society
Volume
85
Issue
8
Start Page
1383
End Page
1391
Published Date
2021-07-21
Remark
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。
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3527号
Diploma Number
甲医第1497号
Granted Date
2021-04-22
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences