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

Naoki Kiyosawa,Yoshiyuki Morishima,Takeshi Yamashita,Naoharu Yagi,Shinya Suzuki,Takuto Arita,Kenji Watanabe,Takayuki Otsuka

doi:10.3390/ijms21072444

Naoki Kiyosawa, Yoshiyuki Morishima + Show 6 more

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https://doi.org/10.3390/ijms21072444

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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.

Highlights

Atrial fibrillation (AF) is the most common cardiac arrhythmia
CHA2DS2-VASc score is a point-based score taking account of selected risk factors, and there are differences in their impacts for the stroke risk
The aim of the present study is to explore potential circulating miRNA biomarkers that are associated with CHA2DS2-VASc score and performing catheter ablation (CA) pursuing the quantitative measurement of the risk and the estimation of the mechanistic background

Summary

Introduction

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Pathophysiological mechanisms of AF are associated with electrical and structural remodeling, including atrial dilatation, cellular hypertrophy, dedifferentiation, fibrosis, cell death and inflammation [1,2,3]. CHA2DS2-VASc score is useful for stratifying AF patient with risk of stroke [6]. There is sufficient evidence that male patients with a CHA2DS2-VASc score ≥2 and female patients with a score ≥3 should be anticoagulated [7,8]. CHA2DS2-VASc score is a point-based score taking account of selected risk factors (i.e., congestive heart failure, hypertension, age 65–74 years, diabetes, female sex and vascular disease, which all count for 1 point, and previous transient ischemic stroke/stroke or age ≥75 years, which count for two points), and there are differences in their impacts for the stroke risk. The age 65–74 years was reported to be consistently associated with the highest risk among the risk factors in AF patients with CHA2DS2-VASc score of 1 [7]. Novel biomarkers are desired to provide mechanistic and quantitative information for patients’ pathophysiological conditions, which would improve patient management on top of CHA2DS2-VASc score

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