Exploratory Analysis of Circulating miRNA Signatures in Atrial Fibrillation Patients Determining Potential Biomarkers to Support Decision-Making in Anticoagulation and Catheter Ablation

Abstract

Novel biomarkers are desired to improve risk management for patients with atrial fibrillation (AF). We measured 179 plasma miRNAs in 83 AF patients using multiplex qRT-PCR. Plasma levels of eight (i.e., hsa-miR-22-3p, hsa-miR-128-3p, hsa-miR-130a-3p, hsa-miR-140-5p, hsa-miR-143-3p, hsa-miR-148b-3p, hsa-miR-497-5p, hsa-miR-652-3p) and three (i.e., hsa-miR-144-5p, hsa-miR-192-5p, hsa-miR-194-5p) miRNAs showed positive and negative correlations with CHA2DS2-VASc scores, respectively, which also showed negative and positive correlations with catheter ablation (CA) procedure, respectively, within the follow-up observation period up to 6-month after enrollment. These 11 miRNAs were functionally associated with TGF-β signaling and androgen signaling based on pathway enrichment analysis. Seven of possible target genes of these miRNAs, namely TGFBR1, PDGFRA, ZEB1, IGFR1, BCL2, MAPK1 and DICER1 were found to be modulated by more than four miRNAs of the eleven. Of them, TGFBR1, PDGFRA, ZEB1 and BCL2 are reported to exert pro-fibrotic functions, suggesting that dysregulations of these eleven miRNAs may reflect pro-fibrotic condition in the high-risk patients. Although highly speculative, these miRNAs may potentially serve as potential biomarkers, providing mechanistic and quantitative information for pathophysiology in daily clinical practice with AF such as possible pro-fibrotic state in left atrium, which would enhance the risk of stroke and reduce the preference for performing CA.

Pilot Study on the Role of Circulating miRNAs for the Improvement of the Predictive Ability of the 2MACE Score in Patients with Atrial Fibrillation

“…Thus, a recent study has demonstrated that miR-22-3p plasma levels tend to be higher in patients with AF and a high CHA 2 DS 2 -VASc score. This suggests that this miRNA is more expressed in patients with high thromboembolic risk, which could provide some information about the pathophysiological conditions of AF patients [ 31 ]. Previously, elevated miR-22-3p serum levels have been shown in patients with heart failure, suggesting that high miR-22-3p circulating levels in serum may reflect intracellular levels in certain tissues and thus may explain the potential functional effect of the miRNA [ 32 ].…”

A Review of Biomarkers for Ischemic Stroke Evaluation in Patients With Non-valvular Atrial Fibrillation

“…Two studies analyzed datasets of Gene Expression Omnibus via bioinformatic analysis, respectively, and identified several genes which were involved in AF-related stroke ( 199 , 200 ). In addition, studies have shown that abnormal expression of non-coding RNAs, such as lncRNA ANRIL, hsa-miR-22-3p, was associated with functional outcome or prognosis in AF patients, and could potentially serve as potential biomarkers for AF-related IS ( 201 , 202 ). On the basis of current research, it can be expected that new and promising genetics biomarkers for AF-related IS will be further discovered in the near future.…”

Liquid Biopsy for Cancer Cachexia: Focus on Muscle-Derived microRNAs

“…Most of these skeletal muscle-derived miRNAs have also been detected in the bloodstream [40,[183][184][185][186][187][188][189][190][191][192][193][194][195][196][197][198][199]. However, to date it is unknown whether their circulating levels are modulated during cancer cachexia in humans.…”