MiR-23a Regulates the Vasculogenesis of Coronary Artery Disease by Targeting Epidermal Growth Factor Receptor

Abstract

Objective: Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. We aimed to investigate the correlation between the levels of circulating miR-23a and the expression of epidermal growth factor receptor (EGFR) in the pathogenesis of patients with coronary heart disease to further explore the mechanism involved in its vasculogenesis.

Method: Three different cohorts, including 13 acute myocardial infarction (AMI) patients, 176 angina pectoris patients, and 127 control subjects, were enrolled to investigate the expression levels of circulating miR-23a in patients with myocardial ischemia and also the relationship between plasma miR-23a and severity of coronary stenosis. Plasma miR-23a levels of participants were examined by real-time quantitative PCR. Simultaneously, plasma cardiac troponin I (cTnI) concentrations were measured by ELISAs. We further detected the correlation of miR-23a and EGFR by molecular and animal assays.

Result: MiR-23a was enriched in not only diseased endothelial progenitor cells (EPCs) but also in the plasma of patients with coronary artery disease (CAD). Besides, we found out miR-23a was able to suppress EGFR expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-23a to the 3'-UTR of EGFR mRNA. Knockdown of miR-23a not only restored EGFR levels and angiogenic activities of diseased EPCs in vitro, but further promoted blood flow recovery in ischemic limbs of mice.

Conclusion: Circulating miR-23a may be a new biomarker for CAD and as a potential diagnostic tool. And increased miR-23a level may be used to predict the presence and severity of coronary lesions in patients with CAD.

Keywords: Coronary artery disease; Disease marker; Endothelial progenitor cells; Epidermal growth factor receptor; MiR-23a.