Diagnostic potential of plasmatic MicroRNA signatures in stable and unstable angina

PLoS One. 2013 Nov 15;8(11):e80345. doi: 10.1371/journal.pone.0080345. eCollection 2013.

Abstract

Purpose: We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina.

Methods: An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated.

Results: Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA.

Conclusions: This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angina, Stable / blood
  • Angina, Stable / diagnosis*
  • Angina, Stable / genetics
  • Angina, Unstable / blood
  • Angina, Unstable / diagnosis*
  • Angina, Unstable / genetics
  • Biomarkers / blood
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / genetics
  • Female
  • Humans
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / metabolism*
  • Middle Aged

Substances

  • Biomarkers
  • MicroRNAs

Grant support

The present study was supported by the following grants: from the Italian Health Ministry: Centro Cardiologico “Monzino” - Programma Strategico (ex art.12 D.Lgs.n.502/92 e s.m.i.), RFPS-2007-2-634780; from Regione Lombardia: Centro Cardiologico “Monzino”, Ospedale di Lecco, Ospedale di Merate - Progetti di Ricerca Indipendente 2009; and from Fondazione Umberto Veronesi : Yuri D'Alessandra - Young Investigator Programme 2013. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.