MicroRNA profiling in the left atrium in patients with non-valvular paroxysmal atrial fibrillation

Abstract

Background: We aimed to identify the miRNA expression profiles in left atrial appendage, with the intention of identifying miRNAs that were significantly associated with non-valvular paroxysmal AF. Methods: The RNA samples were isolated from healthy controls (n=5) and patients with atrial fibrillation (n=8). To confirm the findings obtained by analyzing the miRNA profile, we measured the expression of selected miRNAs in the entire cohort by quantitative PCR. Results: Ten specific miRNAs were found to be differentially expressed between atrial fibrillation and healthy controls with more than a 2-fold change (P<0.05). Consistent with the data obtained for the profile, expression levels of miRNA-155, miRNA-146b-5p and miRNA-19b were significantly increased in patients with atrial fibrillation. Interestingly, levels of miRNA-146b-5p and miRNA-155, which are known to be associated with inflammation, were independently and positively associated with left atrium dimension, atrial fibrillation duration and high sensitivity C-reactive protein levels. By using four Databases (TargetScan, miRanda, Starbase Clip-seq and miRDB) to perform target gene prediction, there were four genes were related to the inflammatory response and fibrosis, and three others encoding cardiac ion channel proteins. As a result of TaqMan qPCR and Western analysis, the relative mRNA and protein expression level of three target genes (DIER-1, TIMP-4 and CACNA1C) were significantly lower in the atrial fibrillation group than that in the healthy control group. Conclusions: Expression of inflammation-associated miRNAs is significantly up-regulated in the left atrial appendage of patients with non-valvular paroxysmal atrial fibrillation, which may play a significant role in electrical and structural remodeling.