Key result
Patients with persistent atrial fibrillation had significantly lower expression of hsa_circ_0004104 (0.6 vs 1.46) and higher TGF-β1 levels compared to those with paroxysmal atrial fibrillation.
Why the study?
The mechanisms underlying the progression of paroxysmal AF to persistent AF remain elusive, and circRNAs may be potential regulators through cardiac fibrosis.
Observational (n=72)
Blinded to clinical data
No
Downregulation of hsa_circ_0004104 is associated with the progression from paroxysmal to persistent atrial fibrillation, potentially by promoting cardiac fibrosis via the TGF-β pathway.
INTRODUCTION: The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression. MATERIALS AND METHODS: 6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-β, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis. RESULTS: PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p < 0.05), compared with PAF patients. The validity of the expression patterns was subsequently validated by RT-PCR in another 60 AF patients (30 PsAF and PAF, respectively). In addition, all the 5 up and down regulated circRNAs were clustered in MAPK and TGF-beta signaling pathway by KEGG pathway analysis. Among the 5 circRNAs, hsa_circ_0004104 was consistently downregulated in PsAF group (0.6 ± 0.33 vs 1.46 ± 0.41, p < 0.001) and predicted to target several AF and/or cardiac fibrosis related miRNAs reported by previous studies. In addition, TGF-β1 level was significantly higher in the PsAF group (5560.23 ± 1833.64 vs 2236.66 ± 914.89, p < 0.001), and hsa_circ_0004104 showed a significant negative correlation with TGF-β1 level (r = - 0.797, p < 0.001). CONCLUSION: CircRNAs dysregulation plays vital roles in AF persistency. hsa_circ_0004104 could be a potential regulator and biomarker in AF persistency by promoting cardiac fibrosis via targeting MAPK and TGF-beta pathways.
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Gao et al. (2021) conducted an observational in Atrial Fibrillation (n=72). Persistent Atrial Fibrillation vs. Paroxysmal Atrial Fibrillation was evaluated on hsa_circ_0004104 expression level (p=<0.001). Patients with persistent atrial fibrillation had significantly lower expression of hsa_circ_0004104 (0.6 vs 1.46) and higher TGF-β1 levels compared to those with paroxysmal atrial fibrillation.
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