Gao Yuanfeng, Dong Ying, Jiang Nan, Zhang Hanrui, Liu Zheng, Wang Qianhui, Fu Yuan, Li Jing, Li Zhiqing, Pan Huize, Zheng Xianing, Zhan Lingyu, Yang Xinchun, Xu Li, Chen Mulei
Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China.
Central Laboratory, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, No. 22, Zhongguancun South Street, Haidian District, Beijing 100081, China.
Cardiovasc Res. 2025 Jul 8;121(7):1036-1051. doi: 10.1093/cvr/cvaf060.
The prediction of atrial fibrillation (AF) progression and post-ablation recurrence is currently based on empirical estimates, leading to suboptimal predictive accuracy. This study investigates whether atrial remodelling, a key factor in the severity of atrial cardiomyopathy, could serve as a shared substrate influencing both AF progression and recurrence. We aimed to identify circular RNAs (circRNAs) associated with atrial remodelling and to evaluate their ability to predict AF progression and recurrence.
We assessed the differential expression of plasma circRNAs between paroxysmal (PAF) and persistent AF (PsAF) patients using microarray analysis. Selected candidate circRNAs were validated through qPCR following rigorous statistical and bioinformatics analysis. circDGCR8 was consistently found to be up-regulated in PsAF compared with PAF patients. Additionally, circDGCR8 was significantly up-regulated in human atrial fibroblasts treated with angiotensin II (AngII). Gain- and loss-of-function studies suggested that circDGCR8 could promote atrial remodelling at cellular level by enhancing collagen production and fibroblast proliferation. Overexpression of circDGCR8 in human cardiac fibroblasts significantly altered the gene expression spectrum, impacting pathways including IL-17 signalling and TNF signalling. Moreover, circDGCR8 levels were positively correlated with atrial fibrosis, as indicated by increased percentages of low voltage zones. The predictive value of circDGCR8 was evaluated in two cohorts: (i) PAF patients monitored for 36 months with progression to PsAF as the endpoint, and (ii) AF patients who underwent radiofrequency ablation followed for 12 months to assess recurrence. In both cohorts, higher level of circDGCR8 was associated with increased risks of AF progression and post-ablation recurrence.
Our results suggest that circDGCR8, associated with atrial remodelling, holds potential as a predictive biomarker for both AF progression and post-ablation recurrence.
目前房颤（AF）进展和消融后复发的预测基于经验估计，导致预测准确性欠佳。本研究调查心房重构这一心房心肌病严重程度的关键因素是否可作为影响AF进展和复发的共同底物。我们旨在鉴定与心房重构相关的环状RNA（circRNA），并评估其预测AF进展和复发的能力。
我们使用微阵列分析评估阵发性房颤（PAF）和持续性房颤（PsAF）患者血浆circRNA的差异表达。经过严格的统计和生物信息学分析后，通过qPCR验证选定的候选circRNA。与PAF患者相比，PsAF患者中circDGCR8始终上调。此外，在用血管紧张素II（AngII）处理的人心房成纤维细胞中，circDGCR8显著上调。功能获得和功能丧失研究表明，circDGCR8可通过增强胶原蛋白生成和成纤维细胞增殖在细胞水平促进心房重构。circDGCR8在人心脏成纤维细胞中的过表达显著改变了基因表达谱，影响包括IL-17信号通路和TNF信号通路在内的多种通路。此外，低电压区百分比增加表明circDGCR8水平与心房纤维化呈正相关。在两个队列中评估了circDGCR8的预测价值：（i）以进展为PsAF为终点对PAF患者进行36个月监测，（ii）对接受射频消融的AF患者随访12个月以评估复发情况。在这两个队列中，较高水平的circDGCR8与AF进展和消融后复发风险增加相关。
我们的结果表明，与心房重构相关的circDGCR8有潜力作为AF进展和消融后复发的预测生物标志物。
