Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans

TLDR

MicroRNAs circulate in human blood and have been increasingly proposed as disease biomarkers. This study aimed to assess whether cardiac‑specific circulating miRNAs could serve as biomarkers for acute myocardial infarction. The authors identified miR‑1, miR‑133a, miR‑499, and miR‑208a as candidate markers by confirming their tissue‑specific expression with real‑time PCR. They found that miR‑208a was undetectable in healthy plasma but rose rapidly after coronary occlusion, was present in 90.9 % of AMI patients within 4 h, and showed the highest sensitivity and specificity for early AMI diagnosis.

Abstract

microRNA (miRNA) is reported to be present in the blood of humans and has been increasingly suggested as a biomarker for diseases. We aim to determine the potential of cardiac-specific miRNAs in circulation to serve as biomarkers for acute myocardial infarction (AMI). By verifying their tissue expression patterns with real-time polymerase chain reaction (PCR) analysis, muscle-enriched miRNAs (miR-1, miR-133a, and miR-499) and cardiac-specific miR-208a were selected as candidates for this study. With miRNA microarray and real-time PCR analyses, miR-1, miR-133a, and miR-499 were present with very low abundance, and miR-208a was absent in the plasma from healthy people. In the AMI rats, the plasma levels of these miRNAs were significantly increased. Especially, miR-208a in plasma was undetected at 0 h, but was significantly increased to a detectable level as early as 1 h after coronary artery occlusion. Further evaluation of the miRNA levels in plasma from AMI patients (n = 33) demonstrated that all four miRNA levels were substantially higher than those from healthy people (n = 30, P < 0.01), patients with non-AMI coronary heart disease (n = 16, P < 0.01), or patients with other cardiovascular diseases (n = 17, P < 0.01). Notably, miR-208a remained undetectable in non-AMI patients, but was easily detected in 90.9% AMI patients and in 100% AMI patients within 4 h of the onset of symptoms. By receiver operating characteristic curve analysis, among the four miRNAs investigated, miR-208a revealed the higher sensitivity and specificity for diagnosing AMI. Elevated cardiac-specific miR-208a in plasma may be a novel biomarker for early detection of myocardial injury in humans.