BACKGROUND Catheter-based pulmonary vein isolation(PVI) is an effective and well-established intervention for symptomatic paroxysmal atrial fibrillation(PAF). Nevertheless, late recurrences of atrial fibrillation(LRAF...BACKGROUND Catheter-based pulmonary vein isolation(PVI) is an effective and well-established intervention for symptomatic paroxysmal atrial fibrillation(PAF). Nevertheless, late recurrences of atrial fibrillation(LRAF) occurring during 3 to 12months are common, and the underlying mechanisms remain elusive. Circular RNAs(circ RNAs) in atrial tissue have been linked to the pathophysiological mechanisms and progression of PAF in a few studies. However, their expression patterns in peripheral blood and regulatory function in LRAF are not clear.METHODS In the present study, the expression profile of circulating circ RNAs in three paired nonvalvular PAF patients with or without LRAF was investigated by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction(q RT-PCR). Bioinformatics analyses, including Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis, and circ RNA/mi RNA regulatory network, were performed to predict the functions and potential regulatory roles of differentially expressed(DE) circ RNAs.RESULTS A total of 12,834 circ RNAs, comprising 5,491 down-regulated and 7,343 up-regulated circ RNAs, were found to be DE in blood smaples from the two groups in peripheral blood between LRAF and non-recurrence control individuals. The most enriched GO categories in terms of molecular function, biological process, and cellular component features were catalytic activity,cellular metabolic process, and intracellular part, respectively. The KEGG enrichment study revealed that the most important metabolic process controlled by DE circ RNAs is endocytosis. In the circ RNA/micro RNAs interaction network, four up-regulated circ RNAs(hsa_circ_0002665, hsa_circ_0001953, hsa_circ_0003831, and hsa_circ_0040533) and one down-regulated circ RNA(hsa_circ_0041103) were predicted to play potential regulatory roles in the pathogenesis of LRAF.CONCLUSIONS This investigation discovered the expression pattern of circulating circ RNAs that is indicative of PAF late recurrence, which may serve as risk markers or therapeutic targets for LRAF after PVI.展开更多
基金supported by Project of National Ministry of Industry and Information Technology(No.2020-0103-3-1-2)National Natural Science Foundation of China(No.81670217).
文摘BACKGROUND Catheter-based pulmonary vein isolation(PVI) is an effective and well-established intervention for symptomatic paroxysmal atrial fibrillation(PAF). Nevertheless, late recurrences of atrial fibrillation(LRAF) occurring during 3 to 12months are common, and the underlying mechanisms remain elusive. Circular RNAs(circ RNAs) in atrial tissue have been linked to the pathophysiological mechanisms and progression of PAF in a few studies. However, their expression patterns in peripheral blood and regulatory function in LRAF are not clear.METHODS In the present study, the expression profile of circulating circ RNAs in three paired nonvalvular PAF patients with or without LRAF was investigated by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction(q RT-PCR). Bioinformatics analyses, including Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis, and circ RNA/mi RNA regulatory network, were performed to predict the functions and potential regulatory roles of differentially expressed(DE) circ RNAs.RESULTS A total of 12,834 circ RNAs, comprising 5,491 down-regulated and 7,343 up-regulated circ RNAs, were found to be DE in blood smaples from the two groups in peripheral blood between LRAF and non-recurrence control individuals. The most enriched GO categories in terms of molecular function, biological process, and cellular component features were catalytic activity,cellular metabolic process, and intracellular part, respectively. The KEGG enrichment study revealed that the most important metabolic process controlled by DE circ RNAs is endocytosis. In the circ RNA/micro RNAs interaction network, four up-regulated circ RNAs(hsa_circ_0002665, hsa_circ_0001953, hsa_circ_0003831, and hsa_circ_0040533) and one down-regulated circ RNA(hsa_circ_0041103) were predicted to play potential regulatory roles in the pathogenesis of LRAF.CONCLUSIONS This investigation discovered the expression pattern of circulating circ RNAs that is indicative of PAF late recurrence, which may serve as risk markers or therapeutic targets for LRAF after PVI.
