{"title":"依普利酮通过ERK1/2 MAPK通路抑制心房颤动自主神经重构","authors":"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","doi":"10.1155/cdr/6041636","DOIUrl":null,"url":null,"abstract":"<p>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.</p><p><b>Methods:</b> 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.</p><p><b>Results:</b> 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.</p><p><b>Conclusions:</b> Eplerenone inhibited atrial autonomic nerve remodeling and the occurrence of AF through modulating the ERK1/2 MAPK pathway.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/6041636","citationCount":"0","resultStr":"{\"title\":\"Eplerenone Inhibits Atrial Autonomic Nerve Remodeling in Atrial Fibrillation Through ERK1/2 MAPK Pathway\",\"authors\":\"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\",\"doi\":\"10.1155/cdr/6041636\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p><p><b>Methods:</b> 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.</p><p><b>Results:</b> 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.</p><p><b>Conclusions:</b> Eplerenone inhibited atrial autonomic nerve remodeling and the occurrence of AF through modulating the ERK1/2 MAPK pathway.</p>\",\"PeriodicalId\":9582,\"journal\":{\"name\":\"Cardiovascular Therapeutics\",\"volume\":\"2025 1\",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/6041636\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cardiovascular Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1155/cdr/6041636\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/cdr/6041636","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Eplerenone Inhibits Atrial Autonomic Nerve Remodeling in Atrial Fibrillation Through ERK1/2 MAPK Pathway
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.
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.
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