Plasma levels of microRNA-499 provide an early indication of perioperative myocardial infarction in coronary artery bypass graft patients

PLoS One. 2014 Aug 11;9(8):e104618. doi: 10.1371/journal.pone.0104618. eCollection 2014.

Abstract

Background: Recent studies indicated that microRNAs (miRNAs, miRs) were important for many biological and pathological processes, and they might be potential biomarkers for cardiovascular diseases. The present study aims to determine the release patterns of miRNAs in cardiac surgery and to analyze the ability of miRs to provide early prediction of perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft (CABG) surgery.

Methodology/principal findings: Thirty on-pump CABG patients were recruited in this study; and miR-499, miR-133a and miR-133b, cardiac troponin I (cTnI) were selected for measurement. Serial plasma samples were collected at seven perioperative time points (preoperatively, and 1, 3, 6, 12, 24, and 48 hours after declamping) and were tested for cTnI and miRs levels. Importantly, miR levels peaked as early as 1-3 hours, whereas cTnI levels peaked at 6 hours after declamping. Peak plasma concentrations of miRs correlated significantly with cTnI (miR-499, r = 0.583, P = 0.001; miR-133a, r = 0.514, P = 0.006; miR-133b, r = 0.437, P = 0.05), indicating the degree of myocardial damage. In addition, 30 off-pump CABG patients were recruited; miR-499 and miR-133a levels were tested, which were significantly lower in off-pump group than in on-pump group. A prospective cohort of CABG patients (n = 120) was recruited to study the predictive power of miRs for PMI. The diagnosis of PMI strictly adhered to the principles of universal definition of myocardial infarction. The data analysis revealed that miR-499 had higher sensitivity and specificity than cTnI, and indicated that miR-499 could be an independent risk factor for PMI.

Conclusion: Our results demonstrate that circulating miR-499 is a novel, early biomarker for identifying perioperative myocardial infarction in cardiac surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Coronary Artery Bypass / adverse effects*
  • Female
  • Humans
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / diagnosis*
  • Myocardial Infarction / etiology
  • Organ Specificity
  • Perioperative Period*
  • Prognosis
  • Time Factors
  • Troponin I / blood

Substances

  • Biomarkers
  • MIRN499 microRNA, human
  • MicroRNAs
  • Troponin I

Grants and funding

This work was supported in part by a grant from the Key Project in the National Science and Technology Pillar Program during the 12th 5-Year Plan Period (Grant No. 2011BAI11B21) and Program for New Century Excellent Talents in University and by the PUMC Youth Fund and the Fundamental Research Funds for the Central Universities (No. 3332013011, to Y. Yao). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.