Abstract 5016: Circulating MicroRNA: A Novel Potential Biomarker for Early Detection of Acute Myocardial Infarction

Background: MicroRNA (miRNA), a class of 19~25-nucletide noncoding RNA, is present in the plasma or serum of humans and other animals, and has been increasingly reported to be the potential biomarkers for several diseases including cancers and liver injury. The objective of this study is to determine the potential of cardiac-specific miRNAs to serve as early-detectable biomarkers in the plasma for acute myocardial infarction (AMI). Methods and Results: With miRNA microarray analysis, we observed the expression profile of miRNAs from the plasma of 5 healthy people. In the plasma, several miRNAs including miR-451 and miR-16 were presented with relative high levels, and the muscle-specific miRNAs, miR-1 and miR-133a were detected with low abundance. However, miR-499 and miR-208, specifically expressed in heart, were undetectable in the plasma. The above results with 6 miRNAs were additionally confirmed by real-time PCR analysis. Interestingly, the levels of miR-1, miR-133a, miR-499, and miR-208, but not miR-451 and miR-16 were significantly increased in the plasma from the rats with coronary artery ligation for 3 hours, compared to those from sham-operated controls (n=6 in both groups). Among them, the elevation of miR-208 was most remarkable. The level of miR-208 in plasma was then examined at various time points (0, 1, 3, 6, 12, 24 hours after coronary artery occlusion). Real-time PCR analysis showed that the amount of miR-208 in plasma became detectable at as early as 1 hour, peaked at 3~6 hours, and declined after 12 hours. Next, the levels of these 6 miRNAs in plasma from 18 patients with AMI, 12 patients with non-AMI CHD and 15 patients with non-CHD were evaluated. The levels of miR-1, miR-133a, miR-499 and miR-208 were substantially higher in AMI group than those in the two other groups. Additionally, the plasma levels of these 4 miRNAs from 5 of 18 AMI patients were decreased during the follow-up investigation. Conclusions: Our results that the levels of miR-1, miR-133a, miR-499 and miR-208 increase in plasma from both AMI rats and patients reveal for the first time that they may serve as potential biomarkers for AMI diagnosis. Importantly, miR-208, increased rapidly at the early stage of AMI, may improve the accuracy in early diagnosis of myocardial damage.