Eplerenone might affect atrial fibrosis in patients with hypertension

Kawasaki, Masato; Yamada, Takahisa; Okuyama, Yuji; Morita, Takashi; Furukawa, Yoichi; Tamaki, Shunsuke; Iwasaki, Yusuke; Kikuchi, Atsushi; Sakata, Yasushi; Fukunami, Masatake

doi:10.1111/pace.13169

Cited by 9 publications

(6 citation statements)

References 41 publications

(42 reference statements)

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“…The RAAS is progressively considered a critical player in cardiac fibrosis development. 53 Angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) [54][55][56][57][58][59] and mineralocorticoid receptor antagonists [60][61][62][63] can reduce atrial fibrosis progression and AF susceptibility, as demonstrated by multiple experimental studies (Table 1). 64 Retrospective trials and meta-analyses of randomized studies demonstrated that administration of ACEIs or ARBs with ACEIs/ARBs of these diseases may have been confounded by indications.…”

Section: Renin-angiotensin-aldosterone System (Raas) Antagonistsmentioning

confidence: 99%

Left atrial fibrosis in atrial fibrillation: Mechanisms, clinical evaluation and management

Chen

2021

J Cellular Molecular Medi

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Atrial fibrillation (AF), the commonest arrhythmia, shows associations with various disease conditions. Mounting evidence indicates that atrial fibrosis is an important part of the arrhythmogenic substrate, with an essential function in the generation of conduction abnormalities that underlie the transition from paroxysmal to persistent AF, which in turn contributes to AF perpetuation. Left atrial (LA) fibrosis is considered a possible major factor and predictor in AF treatment. The present review provides insights into LA fibrosis’ association with AF. The information is focused on clinical aspects and mechanisms, clinical evaluating methods that evaluate fibrosis changes and examining possible options for the prevention of atrial fibrosis.

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Section: Renin-angiotensin-aldosterone System (Raas) Antagonistsmentioning

confidence: 99%

Left atrial fibrosis in atrial fibrillation: Mechanisms, clinical evaluation and management

Chen

2021

J Cellular Molecular Medi

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“… 8 Drugs that prevent myocardial fibrosis and improve heart function might be useful for AF. In recent years, accumulating experimental evidence has suggested that the inhibition of atrial fibrosis using drugs, such as eplerenone, 9 aliskiren, 10 and taurine, 11 effectively inhibits AF susceptibility in patients and animal models.…”

Section: Introductionmentioning

confidence: 99%

Shensong Yangxin capsule reduces atrial fibrillation susceptibility by inhibiting atrial fibrosis in rats with post-myocardial infarction heart failure

Ma¹,

Yin²,

Ma³

et al. 2018

DDDT

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PurposeShensong Yangxin (SSYX) capsule is a traditional Chinese medicine that has been used widely to treat cardiac arrhythmia. This study aimed to assess whether SSYX prevents atrial fibrillation (AF) after chronic myocardial infarction (MI)-induced heart failure and to determine the underlying mechanisms.Materials and methodsThe study included 45 male Sprague Dawley rats. The rats underwent MI induction or sham surgery. One week after MI induction surgery, we performed serial echocardiography and administered SSYX capsule to some rats that experienced MI. After 4 weeks of treatment, AF inducibility was assessed with transesophageal programmed electrical stimulation technology. Additionally, multielectrode array assessment, histological analysis, and Western blot analysis were performed.ResultsAF inducibility was significantly lower in SSYX rats than in MI rats (33.3% vs 73.3%, P<0.05). Additionally, conduction velocities in the left atrium were greater in SSYX rats than in MI rats. Moreover, SSYX decreased left atrial fibrosis, downregulated TGF-β1, MMP-9, TIMP-I, and type I and III collagen expressions, and inhibited the differentiation of cardiac fibroblasts to myofibroblasts.ConclusionSSYX reduces AF inducibility after MI by improving left atrial conduction function via the inhibition of left atrial fibrosis. It prevents the development of an MI-induced vulnerable substrate for AF.

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“…Upstream therapy of atrial fibrillation has become a research hotspot in recent years, such as angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor antagonist (ARB), spironolactone, and statins; spironolactone as one of the upstream treatment drugs has become the focus in the field of electrophysiology. Also, the aldosterone receptor antagonists can alleviate myocardial fibrosis, inhibit the excessive secretion of aldosterone, and reduce the phenomenon of "aldosterone escape" [6][7][8]. ACEI and ARB are popular among scholars for their appropriate therapeutic dose since they do not play an obvious role [9].…”

Section: Discussionmentioning

confidence: 99%

The Dose-Dependent Effects of Spironolactone on TGF-β1 Expression and the Vulnerability to Atrial Fibrillation in Spontaneously Hypertensive Rats

Tang

Chen

Sun

et al. 2021

Cardiology Research and Practice

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Objective. This study tends to assess the dose-dependent effects of spironolactone on TGF-β1 expression, atrial fibrosis, and the vulnerability to atrial fibrillation in spontaneously hypertensive rats (SHRs) and tries to clarify the association of atrial fibrosis with the vulnerability to atrial fibrillation. Methods. Forty 20-week-old male SHRs were randomly divided into 4 groups (10 rats per group): 3 spironolactone groups were lower-dose group (10 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SL), medium-dose group (40 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SM), higher-dose group (80 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SH) and one hypertension group (2 ml saline solution for stomach gavage, group H). Ten matched homologous WKY rats were set as the control group (group C). After 7 weeks of gavage, a multiple electroconductive physiological recorder was used to detect atrial electrical parameters, including P-wave duration, PR interval, and atrial effective refractory period (AERP), the inducibility, and duration of atrial fibrillation. HE staining was used to determine myocardial cell size. Masson staining was used to detect the deposition of the interstitial collagen fibers in atrial muscle. The expression of TGF-β1 was detected by immunohistochemistry and western blot. Results. Compared with group C, the myocardial cell size, atrial fibrosis, TGF-β1 expression, P-wave duration, PR interval, AERP, inducibility, and duration of atrial fibrillation in group H were conspicuously increased ( p < 0.05); compared with group H, there was no significant difference in the myocardial cell size, atrial fibrosis, TGF-β1 expression, and electrophysiological indexes in group SH upon spironolactone intervention ( p > 0.05); compared with group H, the myocardial cell size, atrial fibrosis, the expression of TGF-β1, P-wave duration, PR interval, the inducibility, and duration of atrial fibrillation in the group SL and group SM were all decreased ( p < 0.05); compared with group SM, the effect in the group SL was more prominent ( p < 0.01). Conclusion. Hypertension can lead to cardiomyocyte hypertrophy, deposition of interstitial fibrosis in myocardial tissue, and an increase in the vulnerability to atrial fibrillation. Spironolactone showed a certain dose-dependent effect in SHRs. Lower-dose spironolactone was superior to higher-dose spironolactone in the aspect of reducing hypertensive atrial fibrosis and TGF-β1 expression, as well as preventing the occurrence of atrial fibrillation.

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Eplerenone might affect atrial fibrosis in patients with hypertension

Abstract: Eplerenone reduced the increase of Ad and P-disp with a decrease of PINP and PIIIP, which might translate into reduction of atrial fibrosis. This study showed that eplerenone may be useful as upstream therapy for AF in patients with hypertension.

Cited by 9 publications

References 41 publications

Left atrial fibrosis in atrial fibrillation: Mechanisms, clinical evaluation and management

Left atrial fibrosis in atrial fibrillation: Mechanisms, clinical evaluation and management

Shensong Yangxin capsule reduces atrial fibrillation susceptibility by inhibiting atrial fibrosis in rats with post-myocardial infarction heart failure

The Dose-Dependent Effects of Spironolactone on TGF-β1 Expression and the Vulnerability to Atrial Fibrillation in Spontaneously Hypertensive Rats

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