The radiofrequency ablation may reverse the abnormal miRNA expression in coronary sinus blood of patients with atrial fibrillation

Abstract

Objective: To study the effect of radiofrequency ablation (RFA) on miRNA differential expression in coronary sinus blood (SB) of Atrial Fibrillation (AF) patients, and try to identify the possible pathogenesis of AF and miRNA targets for intervention in future. Methods: 30 AF patients (10 paroxymal, 10 persistent and 10 permanent AF patients) were enrolled, alongside 10 healthy subjects as controls. Peripheral blood (PB) samples were obtained before and at 3 months after RFA respectively. The total RNA was extracted and hybridized with the microRNA chips (microRNA v 18.0), and the differential expression of miRNA and clustering analysis in whole genome were made with Volcano Plot and tMEV software respectively, and validated by Real-time PCR. The target gene analysis of miRNAs was predicted through the Mirbase, Miranda and Targetscan databases. The important miRNAs were made for dual luciferase binding experiment to analyze and validate target genes.Results: There were 142 miRNAs differential expression in SB of pre-operation AF patients compared with PB of patient-self control, in which, 6 miRNAs were increased and 8 miRNAs were decreased significantly (P<0.05). Then, in the compare of PB in AF patients after RFA with which of self-control before RFA, there were 3 miRNAs up-regulated and down-regulated respectively in above increased 6 miRNAs, while miR-1266 was down-regulated 204.17-fold. In above decreased 8 miRNAs, 7 of them were down-regulated again after RFA, while miR-574-3p up-regulated 5.25-fold. SCN5A was the target gene of miR-1266, and CACNA1C was the target gene of miR-4279 confirmed with Luciferase binding experiments. Conclusion: RFA can reverse the abnormal expressions of miRNAs in AF patients. The differential expression of miRNAs in SB can directly reflect the regulatory status of miRNAs in cardiomyocytes in AF attack. MiR-1266 may become the future target for AF intervention.