Circulating MicroRNAs are Promising Novel Biomarkers of Acute Myocardial Infarction

Abstract

Objective Recent studies have revealed that microRNAs (miRNAs) are involved in the regulation of cardiac development, physiologic, and pathologic processes via post-transcriptional control of gene expression. The stable circulating miRNAs offer unique opportunities for the early diagnosis of several diseases. In this study, we examined the circulating miR-133 and miR-328 levels from patients with acute myocardial infarction (AMI). Patients and Methods Twenty-eight control subjects and fifty-one consecutive AMI patients were enrolled. The plasma and whole blood samples from AMI patients were obtained within 24 hours (n=51) and 7 days (n=6) after the onset of AMI symptoms. The circulating miR-133 and miR-328 levels were analyzed using quantitative real-time PCR. Results The miR-133 levels in plasma from AMI patients exhibited a 4.4-fold increase compared with control subjects (p=0.006). Moreover, the increased miR-133 levels in whole blood were comparable with those in plasma samples. In contrast, the miR-328 levels in plasma and whole blood of AMI patients were markedly increased by 10.9-fold and 16.1-fold, respectively, compared to those in control subjects (p=0.033 and p <0.001). The elevated circulating miR-133 and miR-328 levels were recovered to the control levels at 7 days after AMI. In addition, there was a correlation between circulating miR-133 or miR-328 levels and cardiac troponin I. Furthermore, circulating miR-133 or miR-328 showed no significant changes in AMI patients with tachyarrhythmia (n=24) or bradyarrhythmia (n=26) compared to those in patients without arrhythmias. Receiver operating characteristic curve analysis revealed that the areas under the curve of miR-133 or miR-328 in plasma and whole blood were 0.890, 0.702 and 0.810, 0.872, respectively (all p<0.05). Conclusion The miR-133 and miR-328 levels in plasma and whole blood in AMI patients were increased compared to those in control subjects. These miRNAs may represent novel biomarkers of AMI.

Remote Ischemic Preconditioning Preserves Mitochondrial Function and Influences Myocardial MicroRNA Expression in Atrial Myocardium During Coronary Bypass Surgery

“…Circulating levels of the muscle specific miR-133a, miR-133b, and miR-1 are all known to increase in the aftermath of a myocardial infarction. [29][30][31] MiR-133a and miR-133b have nearly identical sequences and likely serve nearly the same biological functions. 31 Elevated circulating levels of miR-133a have been measured as early as 2 hours after onset of chest pain in patients, indicating that alterations in miR-133a expression are a part of a rapid-onset response.…”

Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects

“…Some associations between a particular miRNA and a disease have been investigated in multiple manuscripts, e.g., the up-regulation of miR-1 in the serum and plasma in AMI [46][47][48] and the up-regulation of miR-133 in AMI [46,48,49]. In terms of the link between miR-133 and AMI, Eitel et al [50] described significant correlations with infarct size, microvascular obstruction, and myocardial salvage index.…”

miRNome in myocardial infarction: Future directions and perspective

“…Seven days after onset of AMI symptoms increased circulating miR-133 and miR-328 levels returned to control levels. There has also been observed a correlation between cardiac Troponin I (cTnI) and circulating miR-133 or miR-328 [66] .…”