A MicroRNA Signature Modulated by Colchicine in Acute Coronary Syndrome Patients

Abstract

Background: Circulating microRNAs (miRNAs) may play a pathogenic role in acute coronary syndromes (ACS). We simultaneously profiled miRNA levels across three sites in ACS patients treated with standard therapy or with standard therapy and colchicine 6–24 hrs prior to angiography. Methods: 754 miRNAs were quantified by TaqMan™ real-time polymerase chain reaction from EDTA-plasma in a discovery cohort of 15 patients (N = 3 controls, N = 6 ACS standard therapy, N = 6 ACS standard therapy plus colchicine). Expression levels of circulating microRNAs from the discovery cohort were analysed using ANOVA across groups to identify a set of 51 most differentially regulated miRNAs (P < 0.01). These 51 miRNAs formed our custom panel, to assess expression of these selected miRNAs in a validation cohort of 92 patients (N = 13 controls, N = 40 ACS standard therapy, N = 39 ACS standard therapy plus colchicine). Plasma samples were simultaneously obtained from the coronary sinus, aortic root and right atrium of all study participants. Results: Thirty miRNAs were higher in ACS standard therapy patients compared to controls (fold change >1.5; P < 0.05). Interestingly, seven of these miRNAs higher in ACS returned to levels seen in control subjects after colchicine treatment (fold change >1.5; P < 0.05). Three of these miRNAs were identified as key regulators in inflammatory pathways. In both cohorts, miRNAs were comparable across sampling sites. Conclusion: The levels of specific microRNAs elevated in ACS returned to levels similar to control individuals with colchicine therapy. These miRNAs may mediate ACS (via inflammatory pathways) or increase post-ACS risk, and could be potentially used as biomarkers of treatment efficacy in ACS.