MiR-423 is differentially expressed in patients with stable and unstable coronary artery disease: A pilot study

PLoS One. 2019 May 6;14(5):e0216363. doi: 10.1371/journal.pone.0216363. eCollection 2019.

Abstract

Coronary artery disease (CAD) and acute myocardial infarction (AMI) are the leading causes of death worldwide. Since only a subset of CAD patients develops myocardial infarction, it is likely that unique factors predispose to AMI. Circulating microRNAs represent diagnostic powerful biomarkers for detection of heart injuries and patients' risk stratification. Using an array-based approach, the expression of 84 circulating miRNAs was analyzed in plasma of pooled stable CAD patients (CAD; n = 5) and unstable CAD patients (AMI_T0; n = 5) enrolled within 24 hours from an AMI event. The array experiments showed 27 miRNAs differentially expressed with a two-fold up- or down-regulation (10 up- and 17 down-regulated miRNAs). Among them, miR-423-5p dis-regulation was confirmed in a larger case study (n = 99). Circulating miR-423-5p resulted to be significantly down-regulated within 24 hours from the AMI event (FC = -2, p≤0.05). Interestingly, miR-423-5p expression resulted to be increased (FC = +2; p≤0.005) in a subgroup of the same AMI patients (AMI_T1; n = 11) analyzed after 6 months from the acute event. We extended miR-423-5p expression study on PBMCs (peripheral blood mononuclear cells), confirming also in this tissue its up-regulation at 6 months post-AMI. Receiver operating characteristic analyses (ROC) were performed to detect the power of miR-423-5p to discriminate stable and unstable CAD. In plasma, miR-423-5p expression accurately distinguishes stable and unstable CAD patients (AUC = 0.7143, p≤0.005). Interestingly, the highest discriminatory value (AUC = 0.8529 p≤0.0005) was identified in blood cells, where miR-423-5p expression is able to differentiate unstable CAD patients during an acute event (AMI_T0) from those at six months post-AMI (AMI_T1). Furthermore, cellular miR-423-5p may discriminate also stable CAD patients from unstable CAD patients after six months post-AMI (AUC = 0.7355 p≤0.05). The results of this pilot-study suggest that miR-423-5p expression level both in plasma and blood cells, could represent a new promising biomarker for risk stratification of CAD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis*
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Myocardial Infarction / blood
  • Pilot Projects
  • ROC Curve
  • Risk Assessment
  • Up-Regulation

Substances

  • MIRN423 microRNA, human
  • MicroRNAs

Grants and funding

This study was funded by Fondazione Roma (Sn. NCDS-2013-00000333 to GN and FR) and Bandi Ateneo “Consolidate Foundations” (AmiRNA E82F16000570005 to FA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.