Juanjuan Du

Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long‐term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long‐term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high‐throughput sequencing and TMT‐tagged LC‐MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long‐term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long‐term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce.

Long noncoding RNAs (lncRNAs) have been suggested to play indispensable roles in multiple heart diseases. However, the correlations between lncRNAs and atrial fibrillation (AF) are unclear. In this study, we performed comprehensive lncRNA profiling via high‐throughput RNA sequencing analysis using non‐AF and AF rabbit models. Based on a series of filtering pipelines and bioinformatics analyses, TCONS‐00106987 was selected for further research. TCONS‐00106987 levels were increased in the atria during AF. Moreover, the atrial effective refractory period was shortened and the AF inducibility was increased in vivo in response to lentiviral‐mediated up‐regulation of TCONS‐00106987. TCONS‐00106987 repression resulted in the opposite effects. Further studies indicated that TCONS‐00106987 expression was positively correlated with the expression of the protein‐coding gene KCNJ2. Luciferase reporter assays and whole‐cell patch‐clamp recording confirmed that TCONS‐00106987 promoted electrical remodelling via endogenous competition with microRNA‐26 (miR‐26) to induce transcription of its target gene KCNJ2, thereby increasing inward‐rectifier K⁺ current (I_K1). In conclusion, our study reveals a pathogenic lncRNA‐miRNA regulatory network specific to atrial electrical remodelling that offers potential therapeutic targets for AF.