GW24-e2497 Circulating MicroRNAs as Potential Biomarkers of Coagulation Dysfunction in Patients with Vulnerable Coronary Artery Disease

Objectives The activation of coagulation and fibrinolysis plays a critical role in the incidence of coronary events. MicroRNAs (miRNAs) are small non-coding ribonucleic acids (RNAs) that negatively regulate gene expression on the post-transcriptional level by inhibiting mRNA translation or promoting mRNA degradation. Circulating miRNAs are emerging as potential biomarkers of cardiovascular disease. In vulnerable coronary artery disease (CAD), there may have happened dysregulation in coagulation and fibinolysis. Nevertheless, no data exists about circulating miRNAs correlated with coagulation or fibrinolysis as early risk biomarkers in vulnerable coronary artery disease (CAD). Thus, the aim of this study was to identify the circulating miRNAs signature related to the coagulation or fibrinolytic system in vulnerable CAD. Methods To determine the differential expression of plasma miRNAs, we analysed miRNA expression profile in plasma of patients with chest pain or chest distress attributable to non-cardiac causes (Control group, n = 9) and patients with typical unstable angina (UA group, n = 9) using TaqMan MicroRNA Low Density Array (TLDA). Significance Analysis of Microarrays (SAM) algorithm was used to analyse the array data. To confirm the array data, we detected selected 5 miRNAs (miR-19b, miR-24, miR-25, miR-92a and miR-223) in plasma of another 25 UA patients and 15 controls by TaqMan real-time PCR assays. To address the relationship between miRNAs and coagulation or fibrinolytic system, we performed prediction by two different computer algorithms (miRanda and TargetScan). Results By TLDA and SAM algorithm, we found some differential expression miRNAs can be well clustered between UA group and Control group and a total of 36 miRNAs were significantly up-regulated in UA group. Consistent with the data obtained by the profile, circulating levels of miR-19b, miR-24, miR-25, miR-92a and miR-223 were obviously up-regulated in patients with unstable angina compared with controls. Through predicting in miRanda and TargetScan, we observed 17 miRNAs, including miR-16, miR-19a, miR-19b, miR-24, miR-25, miR-26a, miR-26b, miR-29a, miR-92a, miR-142-3p, miR-195, miR-197, miR-186, miR-223, miR-374a, miR-375 and miR-486-5p, were most probably related to coagulation system rather than fibrinolytic system. Conclusions We report for the first time the signature of circulating miRNAs correlated to coagulation, including miR-16, miR-19a, miR-19b, miR-24, miR-25, miR-26a, miR-26b, miR-29a, miR-92a, miR-142-3p, miR-195, miR-197, miR-186, miR-223, miR-374a, miR-375 and miR-486-5p. These differential expressed miRNAs may become risk biomarkers of vulnerable CAD patients who may suffer from acute coronary events in the future.