Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction

PLoS One. 2014 Sep 3;9(9):e105734. doi: 10.1371/journal.pone.0105734. eCollection 2014.

Abstract

Background: The dysregulated expressions of circulating miRNAs have been detected in various cardiovascular diseases. In our previous experiments, the altered expressions of circulating miRNA-21-5p, miRNA-361-5p and miRNA-519e-5p were confirmed in patients with coronary atherosclerosis by miRNA microarrays. However, the expression levels of these circulating miRNAs in the early phase of acute myocardial infarction (AMI) are still unknown. In the present study, our aims were to examine the expressions of circulating miR-21-5p, miR-361-5p and miR-519e-5p in AMI patients, and assess their clinical applications for diagnosing and monitoring AMI.

Results: Two different cohorts were enrolled in this study. The first cohort included 17 AMI patients and 28 healthy volunteers, and the second cohort included 9 AMI patients, 9 ischemic stroke patients, 8 patients with pulmonary embolism, and 12 healthy volunteers. Quantitative real-time PCR and ELISA assays were preformed to detect the concentrations of plasma miRNAs and cardiac troponin I (cTnI), respectively. The results showed that the plasma levels of miR-21-5p and miR-361-5p were significantly increased in AMI patients, whereas the concentration of circulating miR-519e-5p was reduced. Interestingly, the levels of these circulating miRNAs correlated with the concentrations of plasma cTnI. Receiver operating characteristic (ROC) analysis revealed that these three circulating miRNAs had considerable diagnostic accuracy for AMI with high values of area under ROC curve (AUC). Importantly, combining the three miRNAs significantly increased the diagnostic accuracy. Furthermore, cell experiments demonstrated that these plasma miRNAs may originate from injured cardiomyocytes induced by hypoxia. In addition, the levels of all the three circulating miRNAs in ischemic stroke (IS) and pulmonary embolism (PE) were elevated, whereas the decreased level of plasma miR-519e-5p was only detected in AMI. ROC analysis demonstrated that circulating miR-519e-5p may be a useful biomarker for distinguishing AMI from other ischemic diseases.

Conclusions: Circulating miRNAs may be novel and powerful biomarkers for AMI and they could be potential diagnostic tool for AMI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers / blood
  • Brain Ischemia / blood
  • Brain Ischemia / diagnosis
  • Brain Ischemia / genetics
  • Case-Control Studies
  • Cell Hypoxia
  • Female
  • Humans
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis*
  • Myocardial Infarction / genetics
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / diagnosis
  • Pulmonary Embolism / genetics
  • ROC Curve
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / genetics
  • Troponin I / blood
  • Troponin I / genetics

Substances

  • Biomarkers
  • MIRN21 microRNA, human
  • MIRN361 microRNA, human
  • MIRN519 microRNA, human
  • MicroRNAs
  • Troponin I

Grants and funding

This work was supported by grant from the National Natural Science Foundation of China (No. 31200594 and No. 81070236), Research Fund for the Doctoral Program of Higher Education of China (No. 20120142120056), Key Project of Ministry of Health of the People's Republic of China and Key Project from Hubei Province (JX6A02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.