Circulating miR-185-5p as a Potential Biomarker for Arrhythmogenic Right Ventricular Cardiomyopathy.

Claudia Sacchetto,Zenab Mohseni,Thomas Thum,Giulia Poloni,Robin M W Colpaert,Libero Vitiello,Domenico Corrado,Riccardo Bariani,Alessandra Rampazzo,Martina Calore,Marzia De Bortoli,Chiara Romualdi,Leon J De Windt,Indira G C Vonhögen,Elisa Mazzotti,Luciano Daliento,Barbara Bauce,Alessandra Lorenzon,Ke Xiao

doi:10.3390/cells10102578

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease characterized by progressive myocardial fibro-fatty replacement, arrhythmias and risk of sudden death. Its diagnosis is challenging and often it is achieved after disease onset or postmortem. In this study, we sought to identify circulating microRNAs (miRNAs) differentially expressed in ARVC patients compared to healthy controls. In the pilot study, we screened the expression of 754 miRNAs from 21 ARVC patients and 20 healthy controls. After filtering the miRNAs considering a log fold-change cut-off of ±1, p-value < 0.05, we selected five candidate miRNAs for a subsequent validation study in which we used TaqMan-based real-time PCR to analyse samples from 37 ARVC patients and 30 healthy controls. We found miR-185-5p significantly upregulated in ARVC patients. Receiver operating characteristic analysis indicated an area under the curve of 0.854, corroborating the link of this miRNA and ARVC pathophysiology.

Highlights

Among the causes of heart failure, arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease characterized by progressive myocardial loss and fibrofatty replacement [1,2]
The expression level of 754 circulating miRNAs was analysed in 21 ARVC patients and 20 healthy controls; both cohorts were divided into four pools, each comprising five individuals, except for pool 3, which had six patients
ARVC diagnosis is difficult: it relies on the combination of major and minor task force criteria, it can imply invasive procedures and it is often established postmortem [1,2,3]

Summary

Introduction

Among the causes of heart failure, arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease characterized by progressive myocardial loss and fibrofatty replacement [1,2]. Extracellular miRNAs can circulate and are stable in the biofluids, including plasma, of both animals and humans [8,9], either within membranous vesicles or associated with RNA-binding proteins [10]. For this reason, and due to their implication in several cardiac diseases, miRNAs have recently attracted particular interest as potential non-invasive biomarkers [11]. Few studies have evaluated circulating miRNAs differentially expressed in the heart and in plasma of ARVC patients, showing conflicting results [12,13,14,15]

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Conclusion