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Atrial remodelling and atrial fibrillation self-sustaining: the role of circulating circDGCR8
Yuanfeng Gao1, Ying Dong1, Nan Jiang2
1Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China.
Insights
Circular RNAs (circRNAs) like circDGCR8 may predict atrial fibrillation (AF) progression and recurrence after ablation. This study links circDGCR8 to atrial remodeling, offering a potential new biomarker for AF management.
Area of Science:
- Cardiology
- Molecular Biology
- Biomarker Discovery
Background:
- Current prediction of atrial fibrillation (AF) progression and post-ablation recurrence lacks accuracy.
- Atrial remodeling is a key factor in atrial cardiomyopathy and may influence AF progression and recurrence.
- Identifying reliable biomarkers for AF is crucial for improving patient outcomes.
Purpose of the Study:
- To identify circular RNAs (circRNAs) associated with atrial remodeling.
- To evaluate the predictive potential of identified circRNAs for AF progression and post-ablation recurrence.
Main Methods:
- Differential expression analysis of plasma circRNAs in paroxysmal AF (PAF) versus persistent AF (PsAF) patients using microarray.
- Validation of candidate circRNAs via qPCR, statistical, and bioinformatics analysis.
- In vitro studies (gain/loss-of-function) on human atrial fibroblasts and correlation analysis with atrial fibrosis (low voltage zones).
- Evaluation of circDGCR8 in two clinical cohorts for AF progression and recurrence prediction.
Main Results:
- circDGCR8 was significantly upregulated in PsAF patients and in fibroblasts treated with angiotensin II.
- circDGCR8 promoted atrial remodeling by enhancing collagen production and fibroblast proliferation, affecting IL-17 and TNF signaling pathways.
- Higher circDGCR8 levels correlated with increased atrial fibrosis.
- Elevated circDGCR8 levels predicted increased risk of AF progression and post-ablation recurrence in clinical cohorts.
Conclusions:
- circDGCR8 is associated with atrial remodeling and may serve as a predictive biomarker for AF progression.
- circDGCR8 shows potential as a predictive biomarker for post-ablation AF recurrence.
Aims:
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.
Methods And Results:
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.
Conclusion:
Our results suggest that circDGCR8, associated with atrial remodelling, holds potential as a predictive biomarker for both AF progression and post-ablation recurrence.
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