A Novel miRNA Screen Identifies miRNA-4454 as a Candidate Biomarker for Ventricular Fibrosis in Patients with Hypertrophic Cardiomyopathy.

Tilo Thottakara,Elisabeth Krämer,Paulus Kirchhof,Natalie Lund,Monica Patten,Lucie Carrier

doi:10.3390/biom11111718

Abstract

(1) Background: Left ventricular hypertrophy, myocardial disarray and interstitial fibrosis are the hallmarks of hypertrophic cardiomyopathy (HCM). Access to the myocardium for diagnostic purposes is limited. Circulating biomolecules reflecting the myocardial disease processes could improve the early detection of HCM. Circulating miRNAs have been found to reflect disease processes in several cardiovascular diseases. (2) Methods: We quantified circulating miRNA molecules in the plasma of 24 HCM and 11 healthy controls using the Human v3 miRNA Expression Assay Kit Code set (Nanostring Tech., Seattle, WA, USA) and validated differentially expressed miRNAs using RT-PCR. (3) Results: In comparison to healthy controls, the levels of six miRNAs (miR-1, miR-3144, miR-4454, miR-495-3p, miR-499a-5p and miR-627-3p) were higher in the plasma of HCM patients than healthy individuals (p < 0.05). Of these, higher levels of miR-1, miR-495 and miR-4454 could be validated by real-time PCR. In addition, elevated miR-4454 levels were significantly correlated with cardiac fibrosis, detected by magnetic resonance imaging in HCM patients. (4) Conclusions: Circulating miR-1, miR-495-3p and miR-4454 levels are elevated in the plasma of HCM patients. To the best of our knowledge, this is the first report showing a correlation between miR-4454 levels and cardiac fibrosis in HCM. This suggests miR-4454 as a potential biomarker for fibrosis in these patients.

Highlights

Hypertrophic Cardiomyopathy (HCM) is a common inherited cardiac condition with a prevalence of 1:200 to 1:500 in the general population [1,2]
HCM patients were on different medications as required by the disease state, with some being on multiple medications
Main Findings of the Study being regulated in the plasma of HCM patients using NanoString nCounter as a new screening approach. This is the first study in which miRNA-4454 could be identified as being associated with HCM, and it shows a correlation between miRNA-4454 and hypertrophy and fibrosis in the entire cohort

Summary

Introduction

Hypertrophic Cardiomyopathy (HCM) is a common inherited cardiac condition with a prevalence of 1:200 to 1:500 in the general population [1,2]. It is caused by several mutations in sarcomeric genes leading to myocyte disarray, cardiac remodeling and subsequent ventricular arrhythmia [3]. It is the most frequent cause of sudden cardiac death in young adults and trained athletes, some of which probably remained undiagnosed prior to premature death [4].

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