MiR-486 and miR-92a Identified in Circulating HDL Discriminate between Stable and Vulnerable Coronary Artery Disease Patients

Loredan S Niculescu; Natalia Simionescu; Gabriela M Sanda; Mihaela G Carnuta; Camelia S Stancu; Andreea C Popescu; Mihaela R Popescu; Adelina Vlad; Doina R Dimulescu; Maya Simionescu; Anca V Sima

doi:10.1371/journal.pone.0140958

MiR-486 and miR-92a Identified in Circulating HDL Discriminate between Stable and Vulnerable Coronary Artery Disease Patients

PLoS One. 2015 Oct 20;10(10):e0140958. doi: 10.1371/journal.pone.0140958. eCollection 2015.

Affiliations

¹ Lipidomics Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania.
² Lipidomics Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania; Centre of Advanced Research in Bionanoconjugates and Biopolymers, "Petru Poni" Institute of Macromolecular Chemistry, Iasi, Romania.
³ Cardiology Clinic, Elias University Emergency Hospital, Bucharest, Romania.

Abstract

Small non-coding microRNAs (miRNAs) are implicated in gene regulation, including those involved in coronary artery disease (CAD). Our aim was to identify whether specific serum miRNAs present in the circulating lipoproteins (Lp) are associated with stable or vulnerable CAD patients. A cardiovascular disease-focused screening array was used to assess miRNAs distribution in sera collected from 95 CAD patients: 30 with stable angina (SA), 39 with unstable angina (UA), 26 at one month after myocardial infarction (MI) and 16 healthy control subjects. We found that miR-486, miR-92a and miR-122 presented the highest expression in CAD sera. These miRNA together with miR-125a, miR-146a and miR-33a were further individually analyzed by TaqMan assays. The results were consistent with PCR-array screening data that all of these miRNAs were significantly increased in CAD patients compared to controls. Using a binary logistic regression model, we established that miR-486 and miR-92a in association with some high-density lipoprotein (HDL) components can designate vulnerable CAD patients. Further, all classes of Lp were isolated from sera by density gradient ultracentrifugation. Analysis of the selected miRNAs in each Lp class showed that they were associated mainly with HDL, miR-486 and miR-92a having the highest levels. In UA and MI patients, miR-486 prevailed in HDL2, while miR-92a prevailed in HDL3, and their levels discriminate between stable and vulnerable CAD patients. We identified two circulating miRNAs that in association with some lipid metabolism biomarkers can be used as an additional tool to designate vulnerable CAD patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Angina, Stable / diagnosis*
Angina, Stable / metabolism
Angina, Unstable / diagnosis*
Angina, Unstable / metabolism
Biomarkers / metabolism
Coronary Artery Disease / diagnosis*
Coronary Artery Disease / metabolism
Diagnosis, Differential
Female
Humans
Lipoproteins, HDL / blood*
Male
MicroRNAs / genetics
MicroRNAs / metabolism*
Middle Aged
Myocardial Infarction / diagnosis*
Myocardial Infarction / metabolism
Young Adult

Substances

Biomarkers
Lipoproteins, HDL
MIRN486 microRNA, human
MIRN92 microRNA, human
MicroRNAs

Grants and funding

This work was supported by the Romanian Academy, the Romanian Ministry of National Education PN-II-PT-PCCA-2011-3.1-0184 project (grant number PCCA-127/2012, http://uefiscdi.gov.ro), and cofinanced (GMS) by the European Social Fund through Sectorial Operational Program Human Resources Development 2007-2013 (project number POSDRU/159/1.5/S/ 133391, http://biounibuc.wix.com/unibuc). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.