Circulating long non-coding RNAs NRON and MHRT as novel predictive biomarkers of heart failure

Abstract

This study sought to evaluate the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers for heart failure (HF). We measured the circulating levels of 13 individual lncRNAs which are known to be relevant to cardiovascular disease in the plasma samples from 72 HF patients and 60 non-HF control participants using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) methods. We found that out of the 13 lncRNAs tested, non-coding repressor of NFAT (NRON) and myosin heavy-chain-associated RNA transcripts (MHRT) had significantly higher plasma levels in HF than in non-HF subjects: 3.17 ± 0.30 versus 1.0 ± 0.07 for NRON (P < 0.0001) and 1.66 ± 0.14 versus 1.0 ± 0.12 for MHRT (P < 0.0001). The area under the ROC curve was 0.865 for NRON and 0.702 for MHRT. Univariate and multivariate analyses identified NRON and MHRT as independent predictors for HF. Spearman's rank correlation analysis showed that NRON was negatively correlated with HDL and positively correlated with LDH, whereas MHRT was positively correlated with AST and LDH. Hence, elevation of circulating NRON and MHRT predicts HF and may be considered as novel biomarkers of HF.

Keywords: MHRT; NRON; LncRNA; heart failure; plasma.

Figure 1

Changes in circulating lncRNA levels in patients with HF relative to non‐HF control participants. (A) Circulating levels of lncRNAs were determined by quantitative real‐time RT‐PCR (qPCR) with the plasma samples prepared from HF patients and non‐HF control participants. Note that only NRON and MHRT demonstrated significant differences between patients HF and non‐HF control participants. Data are presented as mean ± S.E.M. ***P < 0.0001, n = 72 for HF and n = 60 for non‐HF control participants. (B & C) Box plot of plasma NRON and MHRT levels, respectively, providing a non‐parametric illustration of numerical data displaying the degree of dispersion (spread), skewness in the data (asymmetry of distribution) and outliers, without making any assumptions of the underlying statistical distribution. ***P < 0.0001, n = 72 for HF and n = 60 for non‐HF control participants.

Figure 2

Receiver operator characteristic analysis of circulating NRON and MHRT for predicting HF. The area under ROC curve was determined to evaluate the predictive power of circulating NRON (A) and MHRT (B) levels for HF using non‐HF participants as control.