Eplerenone Inhibits Atrial Autonomic Nerve Remodeling in Atrial Fibrillation Through ERK1/2 MAPK Pathway

IF 3.4 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Therapeutics Pub Date : 2025-07-28 DOI:10.1155/cdr/6041636

Wei Xu, Cheng-yuan Yu, Ding-yu Wang, Qiang Gao, Song Zhang, Yun Zhang, Yue Yuan, Jing Shi, Yue Li, Guang-zhong Liu, Xiao-ming Shang

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引用次数: 0

Abstract

Atrial autonomic nerve system (ANS) remodeling plays an important role in atrial fibrillation (AF). Mineralocorticoid receptor antagonists (MRAs) have been proved to be effective in preventing atrial structural remodeling. However, the effects of MRA on ANS remodeling in AF and the underlying mechanisms are still unknown.

Methods: Then, 21 rabbits were randomized into sham, pacing, and pacing + eplerenone groups. To verify the effect of aldosterone on ANS remodeling, 18 SD rats were pumped with aldosterone. HL-1 cells were subjected to control treatment or rapid pacing with or without eplerenone or U0126 (an inhibitor of ERK1/2). Atrial sympathetic and parasympathetic remodeling was detected by immunohistochemical staining, Western blotting, and RT-PCR. The circulating neurohormone and atrial electrophysiology were also assessed.

Results: The ERK1/2 MAPK pathway was significantly activated in AF rabbit/HL-1 cell models, resulting in the upregulation of key downstream protein; this effect was significantly restored by eplerenone. Eplerenone prevented the alterations in circulating neurohormone, reduced the mRNA level of sympathetic and parasympathetic-related growth factors, and inhibited the inducibility and duration of AF.

Conclusions: Eplerenone inhibited atrial autonomic nerve remodeling and the occurrence of AF through modulating the ERK1/2 MAPK pathway.

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依普利酮通过ERK1/2 MAPK通路抑制心房颤动自主神经重构

心房自主神经系统重构在心房颤动（AF）中起重要作用。矿物皮质激素受体拮抗剂（MRAs）已被证明对预防心房结构重构有效。然而，MRA对房颤ANS重构的影响及其潜在机制尚不清楚。方法：将21只家兔随机分为假手术组、起搏组和起搏+埃普利酮组。为了验证醛固酮对ANS重构的影响，18只SD大鼠灌胃醛固酮。HL-1细胞接受对照治疗或快速起搏，有或没有eplerenone或U0126 （ERK1/2抑制剂）。采用免疫组化染色、Western blotting和RT-PCR检测心房交感神经和副交感神经重构。同时检测循环神经激素和心房电生理。结果：在AF兔/HL-1细胞模型中，ERK1/2 MAPK通路被显著激活，导致关键下游蛋白上调；eperenone显著地恢复了这种效果。结论：Eplerenone通过调节ERK1/2 MAPK通路抑制心房自主神经重构和房颤的发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular Therapeutics 医学-心血管系统

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged. Subject areas include (but are by no means limited to): Acute coronary syndrome Arrhythmias Atherosclerosis Basic cardiac electrophysiology Cardiac catheterization Cardiac remodeling Coagulation and thrombosis Diabetic cardiovascular disease Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF) Hyperlipidemia Hypertension Ischemic heart disease Vascular biology Ventricular assist devices Molecular cardio-biology Myocardial regeneration Lipoprotein metabolism Radial artery access Percutaneous coronary intervention Transcatheter aortic and mitral valve replacement.