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.