PMID- 32277149 OWN - NLM STAT- MEDLINE DCOM- 20201207 LR - 20210410 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Apr 10 TI - Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements. PG - 6169 LID - 10.1038/s41598-020-63263-6 [doi] LID - 6169 AB - 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. FAU - Becker, Kristian C AU - Becker KC AD - Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Kwee, Lydia Coulter AU - Kwee LC AD - Duke Molecular Physiology Institute, Durham, NC, USA. FAU - Neely, Megan L AU - Neely ML AD - Duke Clinical Research Institute, Durham, NC, USA. FAU - Grass, Elizabeth AU - Grass E AD - Duke Molecular Physiology Institute, Durham, NC, USA. FAU - Jakubowski, Joseph A AU - Jakubowski JA AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Fox, Keith A A AU - Fox KAA AD - University of Edinburgh, Edinburgh, UK. FAU - White, Harvey D AU - White HD AD - Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand. FAU - Gregory, Simon G AU - Gregory SG AD - Duke Molecular Physiology Institute, Durham, NC, USA. FAU - Gurbel, Paul A AU - Gurbel PA AD - Inova Heart & Vascular Institute, Falls Church, VA, USA. FAU - Carvalho, Leonardo de Pinto AU - Carvalho LP AD - Albert Einstein Hospital, Sao Paolo, Brasil. FAU - Becker, Richard C AU - Becker RC AD - University of Cincinnati, Cincinnati, Ohio, USA. FAU - Magnus Ohman, E AU - Magnus Ohman E AD - Duke Clinical Research Institute, Durham, NC, USA. AD - Division of Cardiology, Duke University School of Medicine, Durham, NC, USA. FAU - Roe, Matthew T AU - Roe MT AD - Duke Clinical Research Institute, Durham, NC, USA. AD - Division of Cardiology, Duke University School of Medicine, Durham, NC, USA. FAU - Shah, Svati H AU - Shah SH AD - Duke Molecular Physiology Institute, Durham, NC, USA. AD - Duke Clinical Research Institute, Durham, NC, USA. AD - Division of Cardiology, Duke University School of Medicine, Durham, NC, USA. FAU - Chan, Mark Y AU - Chan MY AD - National University of Singapore, Singapore, Singapore. mark_chan@nuhs.edu.sg. LA - eng PT - Journal Article DEP - 20200410 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Circulating MicroRNA) SB - IM MH - Acute Coronary Syndrome/blood/diagnosis/*genetics/physiopathology MH - Aged MH - Blood Platelets/*physiology MH - Case-Control Studies MH - Circulating MicroRNA/blood/*metabolism MH - Female MH - Gene Expression Profiling MH - Humans MH - Male MH - Middle Aged MH - Platelet Aggregation/*genetics MH - Singapore PMC - PMC7148370 COIS- The TRILOGY-ACS trial (ClinicalTrials.gov number, NCT00699998) and sub-studies were supported by Daiichi Sankyo Incorporated and Eli Lilly and Company. J.A. Jakubowski is a former employee of Eli Lilly. K.A.A. Fox reports receiving research grants from AstraZeneca and the British Heart Foundation. H.D. White reports receiving consulting/advisory board payments from AstraZeneca, Merck Sharpe & Dohme, Roche, and Regado Biosciences, and research grants from Sanofi-Aventis, Eli Lilly, The Medicines Company, NIH, Roche, Merck Sharpe & Dohme, AstraZeneca, GlaxoSmithKline, and Daiichi Sankyo Pharma Development. S.G. Gregory reports receiving research grants from NIH, DoD, and the Prostate Cancer Foundation. P.A. Gurbel reports receiving grants from: The National Institutes of Health, Bayer, Medicure, Instrumentation Labs, USWorld Medicals, Haemonetics, Amgen, Idorsia, Ionis, Janssen, and Merck. He reports receiving honoraria, payment for lectures, and consultations on speakers' bureaus from: Bayer, Janssen, Merck, UptoDate, and Medicure. He holds patents in the area of personalized antiplatelet therapy and interventional cardiology. R.C. Becker reports receiving grant support from AstraZeneca, BMS/Sanofi Partnership, Johnson & Johnson, Bayer, honoraria from AstraZeneca and Daiichi/Eli Lilly and consultant for Portola Pharmaceuticals, and Boehringer-Ingelheim. E.M. Ohman reports receiving research grants from Daiichi Sankyo, Eli Lilly, and Gilead, and consulting/ advisory board payments from AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, The Medicines Company, WebMD, Abiomed, Sanofi-Aventis, and Janssen. M.T. Roe reports receiving consulting/advisory board/other payments from Eli Lilly, Janssen, Elsevier, AstraZeneca, Merck, Amgen, and Bristol-Myers Squibb. S.H. Shah reports receiving research grants from NIH, NHLBI, Health Effects Institute and the American Heart Association and family members receiving consulting/ advisory board payments from Biosense Webster and Apama Medical. M.Y. Chan receives salary support from a National Medical Research Council (Singapore) Clinician-Scientist Award (NMRC/CSA-INV/0001/2016) and a research grant from Eli Lilly. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2020/04/12 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/04/10 CRDT- 2020/04/12 06:00 PHST- 2019/09/09 00:00 [received] PHST- 2020/03/24 00:00 [accepted] PHST- 2020/04/12 06:00 [entrez] PHST- 2020/04/12 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/04/10 00:00 [pmc-release] AID - 10.1038/s41598-020-63263-6 [pii] AID - 63263 [pii] AID - 10.1038/s41598-020-63263-6 [doi] PST - epublish SO - Sci Rep. 2020 Apr 10;10(1):6169. doi: 10.1038/s41598-020-63263-6.