Yunping Zhou , Tianxin Ye , Fangcong Yu , Zhuonan Song , Longbo Wang , Cui Zhang , Bo Yang , Jinxiu Yang , Xingxiang Wang
{"title":"抑制P2X7受体可减轻异丙肾上腺素诱导大鼠心房颤动的易感性。","authors":"Yunping Zhou , Tianxin Ye , Fangcong Yu , Zhuonan Song , Longbo Wang , Cui Zhang , Bo Yang , Jinxiu Yang , Xingxiang Wang","doi":"10.1016/j.bbrc.2025.151340","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Atrial fibrillation (AF) is a common cardiac arrhythmia that is characterized by atrial electrical remodeling. The P2X7 receptor (P2X7R), an ATP-gated ion channel, has been implicated in cardiovascular pathologies; however, its role in atrial electrical remodeling remains unclear. This study investigated whether inhibition of P2X7R could mitigate isoproterenol (ISO)-induced atrial electrical remodeling in rats and explored the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Two gene expression profiles related to AF (GSE79768 and GSE10598) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using GEO2R. Mendelian randomization (MR) investigated the causal relationship between P2X7R expression and AF. Enrichment analysis was also conducted. An animal model was established via intraperitoneal injection of ISO for 2 weeks. The rats were divided into three groups: control (CTL), ISO, and ISO + Brilliant Blue G (BBG). Cardiac electrophysiological parameters were assessed using programmed electrical stimulation. Myocardial fibrosis and hypertrophy were evaluated using Sirius Red and Wheat Germ Agglutinin staining, respectively. P2X7R abundance was assessed using immunofluorescence, and relevant proteins were detected by Western blotting.</div></div><div><h3>Results</h3><div>GEO2R and MR analyses indicated a correlation between P2X7R expression and AF. Rats in the ISO group exhibited increased P2X7R levels, abnormal cardiac electrophysiology, altered ion channel protein expression, myocardial hypertrophy, and fibrosis. Enrichment analysis indicated that oxidative stress responses might be involved, and Western blotting showed significantly elevated levels of NOX, CaMKII, and associated proteins. BBG (P2X7R inhibitor) treatment mitigated these effects.</div></div><div><h3>Conclusions</h3><div>P2X7R was associated with AF, and inhibition of P2X7R curbed electrical and structural remodeling in ISO-induced AF, potentially via the NOX/CaMKII pathway.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"749 ","pages":"Article 151340"},"PeriodicalIF":2.2000,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Inhibition of P2X7 receptor mitigates atrial fibrillation susceptibility in isoproterenol-induced rats\",\"authors\":\"Yunping Zhou , Tianxin Ye , Fangcong Yu , Zhuonan Song , Longbo Wang , Cui Zhang , Bo Yang , Jinxiu Yang , Xingxiang Wang\",\"doi\":\"10.1016/j.bbrc.2025.151340\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Atrial fibrillation (AF) is a common cardiac arrhythmia that is characterized by atrial electrical remodeling. The P2X7 receptor (P2X7R), an ATP-gated ion channel, has been implicated in cardiovascular pathologies; however, its role in atrial electrical remodeling remains unclear. This study investigated whether inhibition of P2X7R could mitigate isoproterenol (ISO)-induced atrial electrical remodeling in rats and explored the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Two gene expression profiles related to AF (GSE79768 and GSE10598) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using GEO2R. Mendelian randomization (MR) investigated the causal relationship between P2X7R expression and AF. Enrichment analysis was also conducted. An animal model was established via intraperitoneal injection of ISO for 2 weeks. The rats were divided into three groups: control (CTL), ISO, and ISO + Brilliant Blue G (BBG). Cardiac electrophysiological parameters were assessed using programmed electrical stimulation. Myocardial fibrosis and hypertrophy were evaluated using Sirius Red and Wheat Germ Agglutinin staining, respectively. P2X7R abundance was assessed using immunofluorescence, and relevant proteins were detected by Western blotting.</div></div><div><h3>Results</h3><div>GEO2R and MR analyses indicated a correlation between P2X7R expression and AF. Rats in the ISO group exhibited increased P2X7R levels, abnormal cardiac electrophysiology, altered ion channel protein expression, myocardial hypertrophy, and fibrosis. Enrichment analysis indicated that oxidative stress responses might be involved, and Western blotting showed significantly elevated levels of NOX, CaMKII, and associated proteins. BBG (P2X7R inhibitor) treatment mitigated these effects.</div></div><div><h3>Conclusions</h3><div>P2X7R was associated with AF, and inhibition of P2X7R curbed electrical and structural remodeling in ISO-induced AF, potentially via the NOX/CaMKII pathway.</div></div>\",\"PeriodicalId\":8779,\"journal\":{\"name\":\"Biochemical and biophysical research communications\",\"volume\":\"749 \",\"pages\":\"Article 151340\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-02-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical and biophysical research communications\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0006291X25000543\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical and biophysical research communications","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0006291X25000543","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/18 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：心房颤动（AF）是一种以心房电重构为特征的常见心律失常。P2X7受体（P2X7R）是一种atp门控离子通道，与心血管疾病有关；然而，其在心房电重构中的作用尚不清楚。本研究探讨抑制P2X7R是否能减轻异丙肾上腺素（ISO）诱导的大鼠心房电重构，并探讨其机制。方法：从gene expression Omnibus （GEO）数据库中下载两个与AF相关的基因表达谱（GSE79768和GSE10598）。采用GEO2R筛选差异表达基因（DEGs）。孟德尔随机化研究了P2X7R表达与AF之间的因果关系，并进行了富集分析。通过腹腔注射ISO建立动物模型2周。将大鼠分为对照组（CTL）、ISO组和ISO +亮蓝G组（BBG）。采用程序化电刺激评估心脏电生理参数。用天狼星红染色和小麦胚芽凝集素染色分别评价心肌纤维化和心肌肥大。免疫荧光法检测P2X7R丰度，Western blotting检测相关蛋白。结果：GEO2R和MR分析显示P2X7R表达与房颤相关。ISO组大鼠表现为P2X7R水平升高、心脏电生理异常、离子通道蛋白表达改变、心肌肥大和纤维化。富集分析表明可能涉及氧化应激反应，Western blotting显示NOX， CaMKII和相关蛋白水平显著升高。BBG （P2X7R抑制剂）治疗减轻了这些影响。结论：P2X7R与房颤相关，抑制P2X7R可能通过NOX/CaMKII途径抑制iso诱导房颤的电和结构重构。
Inhibition of P2X7 receptor mitigates atrial fibrillation susceptibility in isoproterenol-induced rats
Background
Atrial fibrillation (AF) is a common cardiac arrhythmia that is characterized by atrial electrical remodeling. The P2X7 receptor (P2X7R), an ATP-gated ion channel, has been implicated in cardiovascular pathologies; however, its role in atrial electrical remodeling remains unclear. This study investigated whether inhibition of P2X7R could mitigate isoproterenol (ISO)-induced atrial electrical remodeling in rats and explored the underlying mechanisms.
Methods
Two gene expression profiles related to AF (GSE79768 and GSE10598) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using GEO2R. Mendelian randomization (MR) investigated the causal relationship between P2X7R expression and AF. Enrichment analysis was also conducted. An animal model was established via intraperitoneal injection of ISO for 2 weeks. The rats were divided into three groups: control (CTL), ISO, and ISO + Brilliant Blue G (BBG). Cardiac electrophysiological parameters were assessed using programmed electrical stimulation. Myocardial fibrosis and hypertrophy were evaluated using Sirius Red and Wheat Germ Agglutinin staining, respectively. P2X7R abundance was assessed using immunofluorescence, and relevant proteins were detected by Western blotting.
Results
GEO2R and MR analyses indicated a correlation between P2X7R expression and AF. Rats in the ISO group exhibited increased P2X7R levels, abnormal cardiac electrophysiology, altered ion channel protein expression, myocardial hypertrophy, and fibrosis. Enrichment analysis indicated that oxidative stress responses might be involved, and Western blotting showed significantly elevated levels of NOX, CaMKII, and associated proteins. BBG (P2X7R inhibitor) treatment mitigated these effects.
Conclusions
P2X7R was associated with AF, and inhibition of P2X7R curbed electrical and structural remodeling in ISO-induced AF, potentially via the NOX/CaMKII pathway.
期刊介绍：
Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research. The development of the "Breakthroughs and Views" section brings the minireview format to the journal, and issues often contain collections of special interest manuscripts. BBRC is published weekly (52 issues/year).Research Areas now include: Biochemistry; biophysics; cell biology; developmental biology; immunology
; molecular biology; neurobiology; plant biology and proteomics
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
