Signature of Serum miR-199a/b in Coronary Artery Bypass Graft Surgery

Abstract

Objective: microRNAs (miRNAs) have important potential as biomarkers in the diagnosis and prognosis of ischemia/reperfusion (I/R) injury in coronary artery bypass grafting surgery (CABG). This study investigated the relationship between preoperative (preop) and postoperative (post-op) cardiac parameters and miRNA expressions in CABG. Methods: We analyzed a total of 94 individuals (CABG, n= 46 and healthy control, n=48). Quantitative real-time polymerase chain reaction (qRT) was performed to determine plasma miRNA expressions (miR-21, miR-181a, miR-199a, miR-199b, and miR-320a-5p) in triplicates: before surgery, 1 hour after surgery, and 24 hours after surgery. The target genes and pathways of miRNA were determined using bioinformatic analysis. The biomarker potentials of miRNAs were evaluated with receiver operating characteristic (ROC) curve analysis. Results: All miRNAs were significantly downregulated (p < 0.05). Troponin I, LVEF, CPK, and CK-MB were found to be statistically significant for operation groups (p < 0.05). miRNA expressions and cardiac markers were associated with troponin I and/or CK-MB. In ROC analyses, miR-199a was a good diagnostic marker. CREBRF and ZNF704 genes may be a target for these miRNAs. Conclusions: Downregulation of miR-199a has a regulatory role in ischemia/reperfusion. They may contribute to CABG pathology through these two genes involved in signaling cascades to turn on protein response and ion binding.