1. Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements
- Author
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Lydia Coulter Kwee, Kristian C. Becker, Harvey D. White, Megan L. Neely, Joseph A. Jakubowski, Mark Y. Chan, Svati H. Shah, Leonardo de Pinto Carvalho, Elizabeth Grass, Matthew T. Roe, Simon G. Gregory, Keith A.A. Fox, Paul A. Gurbel, E. Magnus Ohman, and Richard C. Becker
- Subjects
Blood Platelets ,Male ,Platelets ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Acute coronary syndrome ,Platelet Aggregation ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Article ,Platelet reactivity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,microRNA ,Humans ,Medicine ,Platelet ,Circulating MicroRNA ,Clinical genetics ,Acute Coronary Syndrome ,lcsh:Science ,Aged ,Singapore ,Multidisciplinary ,business.industry ,Gene Expression Profiling ,lcsh:R ,Middle Aged ,medicine.disease ,Fold change ,030104 developmental biology ,medicine.anatomical_structure ,Case-Control Studies ,miRNAs ,Cohort ,Female ,lcsh:Q ,business ,Artery - Abstract
Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker of platelet function, in two cohorts following a non-ST elevation acute coronary syndrome (NSTE-ACS) event. First, non-targeted microRNA concentrations and PR were compared in a case (N = 77) control (N = 76) cohort within the larger TRILOGY-ACS trial. MicroRNA significant in this analysis plus CVD-associated microRNAs from the literature were then quantified by targeted rt-PCR in the complete TRILOGY-ACS cohort (N = 878) and compared with matched PR samples. Finally, microRNA significant in the non-targeted & targeted analyses were verified in an independent post NSTE-ACS cohort (N = 96). From the non-targeted analysis, 14 microRNAs were associated with PR (Fold Change: 0.91–1.27, p-value: 0.004–0.05). From the targeted analysis, five microRNAs were associated with PR (Beta: −0.09–0.22, p-value: 0.004–0.05). Of the 19 significant microRNAs, three, miR-15b-5p, miR-93 and miR-126, were consistently associated with PR in the TRILOGY-ACS and independent Singapore post-ACS cohorts, suggesting the measurement of circulating microRNA concentrations may report on dynamic changes in platelet biology following a cardiovascular ischemic event.
- Published
- 2020