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Heart Vessels. 2019 Mar 14. doi: 10.1007/s00380-019-01377-2. [Epub ahead of print]

Edoxaban suppresses the progression of atrial fibrosis and atrial fibrillation in a canine congestive heart failure model.

Author information

1
Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. tsujino.ys35@gmail.com.
2
Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
3
Department of Legal Medicine, University of Toyama, Toyama, Japan.

Abstract

Coagulation factor Xa activates the protease-activated receptor 2 (PAR2) and causes tissue fibrosis; however, the effects of Xa inhibitor edoxaban on atrial fibrosis and atrial fibrillation (AF) have not been investigated. We examined the effect of edoxaban on the progression of atrial fibrosis in a canine congestive heart failure (CHF) model. Beagle dogs were assigned to sham, placebo, and edoxaban groups (n = 6/group). Dogs of the placebo or edoxaban groups received 19 days of medication with daily oral placebo or edoxaban, respectively, followed by 14 days of ventricular tachypacing. Dogs of the sham group had no medication or pacing. Ventricular tachypacing prolonged AF duration in dogs of the placebo group (159 ± 41 s, p < 0.01 vs. sham); however, this effect was suppressed by edoxaban treatment. Compared with the sham group, tachypacing alone also significantly increased the atrial fibrotic area (2.9 ± 0.1% vs. 7.8 ± 0.4%, p < 0.01), PAR2 expression (1.0 ± 0.1 vs. 1.8 ± 0.3, p < 0.05), and atrial fibronectin expression (1.0 ± 0.2 vs. 2.0 ± 0.2, p < 0.01). These responses were suppressed by edoxaban treatment (area 5.9 ± 0.4%, p < 0.01; PAR2 1.1 ± 0.1, p < 0.05; fibronectin 1.2 ± 0.2, p < 0.05 vs. placebo). Edoxaban showed suppressive effects on atrial remodeling, AF progression, and excessive expressions of PAR2 and fibronectin in a canine CHF model. The suppression of the Xa/PAR2 pathway might be a potential pharmacological target of edoxaban.

KEYWORDS:

Atrial fibrillation; Atrial remodeling; Edoxaban; PAR2

PMID:
30874892
DOI:
10.1007/s00380-019-01377-2

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