The Expression Levels of Plasma micoRNAs in Atrial Fibrillation Patients

Abstract

BackgroundMicroRNA (miRNA) has been found in human blood. It has been increasingly suggested that miRNAs may serve as biomarkers for diseases. We examined the potential of circulating miRNA to serve as predictors of atrial fibrillation (AF).Methodology/Principal FindingsDuring the discovery stage of this project, we used massively parallel signature sequencing (MPSS) to carry out an in-depth analysis of the miRNA expression profile (miRNome) in 5 healthy controls, 5 patients with paroxysmal atrial fibrillation (PAF) alone, and 5 patients with persistent atrial fibrillation (PersAF) alone. Twenty-two specific miRNAs were found to be dysregulated in each PAF group, PersAF group, or control group. Four candidate microRNAs (miRNA-146a, miRNA-150, miRNA-19a, and miRNA-375) met our selection criteria and were evaluated in an independent cohort of 90 plasma samples using TaqMan miRNA quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR). We found miRNA-150 levels to be reduced by a factor of approximately 17 in PAF relative to controls and a factor of approximately 20 in PersAF relative to controls (P<.0001). Logistic regression analyses were carried out to evaluate the reduced miRNA-150 expression levels (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.5 to 3.57, P<0.001), age (OR 1.1, 95% CI 1.36 to 2.73, P<0.001), and Left atrial diameter (LAD) (OR 1.5, 95% CI 1.36 to 1.8, P<0.001). Each was independently associated with AF. Much of the identified target genes related to AF were part of the inflammatory response system. We found that plasma levels of CRP were negatively correlated with the plasma levels of miRNA-150.Conclusions/SignificanceIn summary, we firstly found that plasma miRNA-150 levels in from AF patients were substantially lower than that from healthy people. Circulating reduced miRNA-150 was significantly associated with AF.

Combined Analysis of Human and Experimental Murine Samples Identified Novel Circulating MicroRNAs as Biomarkers for Atrial Fibrillation

“…16 Liu et al identified that downregulation of miR-150 in plasma was significantly associated with AF. 17 The downregulation of miR-150 in patients with AF was also reported by other studies 19, 20 and still other studies have separately reported changes in the expression of miR-21, miR-29, and miR-328 in AF patients. 18,19,21 A recent study showed that the plasma miR-409-3p and miR-432 levels were reduced in association with AF, and these expression levels were restored after successful catheter ablation.…”

Pitx2 -microRNA pathway that delimits sinoatrial node development and inhibits predisposition to atrial fibrillation

“…Experiments looking at miR-17-92 showed that miR-19a expression was reduced in serum of patients with persistent AF (41). In patients with AF and mitral stenosis, several individual members of the miR-17-92 cluster, including miR-17, miR-19a, miR-19b, and miR-20a, were significantly down-regulated compared with healthy individuals (42).…”

microRNAs in cardiovascular disease – clinical application

“…Cellular analyses from atria of AF patients showed significantly elevated levels of miR-21, which were linked to an involvement of its target Sprouty 1 (Spry1) [42]. In one of the first clinical evaluations, Liu et al reported reduced miR-150 plasma levels in AF patients compared with healthy controls and a significant association of miR-150 with AF [125], indicating the potential use of miRNAs as circulating biomarkers for AF. Further clinical studies followed, predominantly undertaken in atrial tissue and analyzing cellular miRNAs.…”