Regulation of Platelet Reactivity Identified Through MicroRNA Profiling in Acute Coronary Syndrome

Introduction: Recent studies suggest an association between changes in platelet-specific microRNAs (miRs) and changes in platelet reactivity. However, molecular pathways that govern platelet reactivity are incompletely characterized. We hypothesize that miRs expressed in plasma are associated with measured platelet reactivity in the TRILOGY-ACS cohort and highlight the genomic regulatory architecture of platelet reactivity. Methods: The study included 712 patients with non-ST elevation acute coronary syndrome (NSTEACS) enrolled in the TRILOGY-ACS trial. Plasma samples collected prior to anti-platelet therapy randomization were used to determine P2Y12 Reaction Units (PRU) measured on the VerifyNow system as well as the concentration of 35 miR species known to be involved in cardiovascular development and disease. We tested for association between PRU and miR expression using multivariable linear regression, adjusting for age, sex, race, prior clopidogrel and aspirin status, diabetes and cytochrome 2C19 gen...