Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements.

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.

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Published Version (Please cite this version)

10.1038/s41598-020-63263-6

Publication Info

Becker, Kristian C, Lydia Coulter Kwee, Megan L Neely, Elizabeth Grass, Joseph A Jakubowski, Keith AA Fox, Harvey D White, Simon G Gregory, et al. (2020). Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements. Scientific reports, 10(1). p. 6169. 10.1038/s41598-020-63263-6 Retrieved from https://hdl.handle.net/10161/20751.

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Scholars@Duke

Neely

Megan Lee Neely

Associate Professor of Biostatistics & Bioinformatics

Survival Analysis; Longitudinal Analysis; Joint Modeling; Prediction Modeling and Metrics; Biomarkers; Applications in Pulmonology and Lung Transplant; Statistical Education

Gregory

Simon Gray Gregory

Professor in Neurosurgery

Dr. Gregory is a tenured Professor and Director of the Brain Tumor Omics Program (BTOP) in the Duke Department of Neurosurgery, the Vice Chair of Research in the Department of Neurology, and Director of the Molecular Genomics Core at the Duke Molecular Physiology Institute. 

As a neurogenomicist, Dr. Gregory applies the experience gained from leading the sequencing of chromosome 1 for the Human Genome Project to elucidating the mechanisms underlying multi-factorial diseases using genetic, genomic, and epigenetic approaches. Dr. Gregory’s primary areas of research involve understanding the molecular processes associated with disease development and progression in brain tumors and Alzheimer’s disease, novel drug induced white matter injury repair in multiple sclerosis, and social and behavioral response to oxytocin treatment animal models of autism. 

He is broadly regarded across Duke as a leader in the development of novel single cell and spatial molecular technologies towards understanding the pathogenic mechanisms of disease development. Dr. Gregory is also the Section Chair of Genomics and Epigenetics at the DMPI and Director of the Duke Center of Autoimmunity and MS in the Department of Neurology.

Paul Alfred Gurbel

Adjunct Professor in the Department of Medicine
Roe

Matthew Todd Roe

Adjunct Professor in the Department of Medicine

My clinical activities focus upon general, preventive, and acute care cardiology.  I round regularly on the inpatient general cardiology and coronary care unit (CCU) services and i have a particular interest in the treatment and management of patients with acute myocardial infarction and cardiogenic shock.  In my outpatient clinic, I care for patients with a variety of cardiovascular conditions include chronic coronary artery disease, hypertension, hyperlipidemia, atrial fibrillation, congestive heart failure, aortic aneurysms, and peripheral arterial disease.  In this setting, I have a particular interest in cardiovascular risk factor modification and long-term treatment strategies to mitigate the risk of future cardiovascular events.

My research activities at the Duke Clinical Research Institute focus upon the coordination and leadership of randomized clinical trials evaluating new therapies for a variety of cardiovascular conditions (acute myocardial infarction, hyperlipidemia, coronary stent placement, peripheral arterial disease, and coronary artery disease) as well as observational registries that evaluate the same disease conditions.

Shah

Svati Hasmukh Shah

Ursula Geller Distinguished Professor of Research in Cardiovascular Diseases

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