Inhibition of P2X7 receptor mitigates atrial fibrillation susceptibility in isoproterenol-induced rats

被引:0
作者
Zhou, Yunping [1 ]
Ye, Tianxin [1 ]
Yu, Fangcong [1 ]
Song, Zhuonan [1 ]
Wang, Longbo [1 ]
Zhang, Cui [2 ,3 ,4 ]
Yang, Bo [2 ,3 ,4 ]
Yang, Jinxiu [1 ]
Wang, Xingxiang [1 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Cardiol, Hangzhou, Zhejiang, Peoples R China
[2] Wuhan Univ, Dept Cardiol, Renmin Hosp, Wuhan 430060, Peoples R China
[3] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Peoples R China
[4] Hubei Key Lab Cardiol, Wuhan 430060, Peoples R China
基金
中国国家自然科学基金;
关键词
Atrial fibrillation; Mendelian randomization; NADPH oxidase; CaMKII; FIBROSIS; DYNAMICS;
D O I
10.1016/j.bbrc.2025.151340
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:16
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