title: Association of MicroRNAs and YRNAs With Platelet Function.
abstract: BACKGROUND
  Platelets shed microRNAs (miRNAs). Plasma miRNAs change on platelet inhibition. It is unclear whether plasma miRNA levels correlate with platelet function.
  
  
  OBJECTIVE
  To link small RNAs to platelet reactivity.
  
  
  RESULTS
  Next-generation sequencing of small RNAs in plasma revealed 2 peaks at 22 to 23 and 32 to 33 nucleotides corresponding to miRNAs and YRNAs, respectively. Among YRNAs, predominantly, fragments of RNY4 and RNY5 were detected. Plasma miRNAs and YRNAs were measured in 125 patients with a history of acute coronary syndrome who had undergone detailed assessment of platelet function 30 days after the acute event. Using quantitative real-time polymerase chain reactions, 92 miRNAs were assessed in patients with acute coronary syndrome on different antiplatelet therapies. Key platelet-related miRNAs and YRNAs were correlated with platelet function tests. MiR-223 (rp=0.28; n=121; P=0.002), miR-126 (rp=0.22; n=121; P=0.016), and other abundant platelet miRNAs and YRNAs showed significant positive correlations with the vasodilator-stimulated phosphoprotein phosphorylation assay. YRNAs, miR-126, and miR-223 were also among the small RNAs showing the greatest dependency on platelets and strongly correlated with plasma levels of P-selectin, platelet factor 4, and platelet basic protein in the population-based Bruneck study (n=669). A single-nucleotide polymorphism that facilitates processing of pri-miR-126 to mature miR-126 accounted for a rise in circulating platelet activation markers. Inhibition of miR-126 in mice reduced platelet aggregation. MiR-126 directly and indirectly affects ADAM9 and P2Y12 receptor expression.
  
  
  CONCLUSIONS
  Levels of platelet-related plasma miRNAs and YRNAs correlate with platelet function tests in patients with acute coronary syndrome and platelet activation markers in the general population. Alterations in miR-126 affect platelet reactivity.
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kaudewitz
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Philipp
authors.initials: P
authors.lastname: Skroblin
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Lukas H
authors.initials: LH
authors.lastname: Bender
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Temo
authors.initials: T
authors.lastname: Barwari
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, UK.|Department of Neurology, Medical University Innsbruck, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Willeit
authors.affiliation: Department of Neurology, Medical University Innsbruck, Austria.
authors.forename: Raimund
authors.initials: R
authors.lastname: Pechlaner
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Sunderland
authors.affiliation: Department of Neurology, Medical University Innsbruck, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Willeit
authors.affiliation: Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors.forename: Allison C
authors.initials: AC
authors.lastname: Morton
authors.affiliation: William Harvey Research Institute, Queen Mary University of London, UK.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Armstrong
authors.affiliation: William Harvey Research Institute, Queen Mary University of London, UK.
authors.forename: Melissa V
authors.initials: MV
authors.lastname: Chan
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Lu
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.affiliation: Biomedical Research Centre, King's College London, UK.
authors.forename: Filipe
authors.initials: F
authors.lastname: Gracio
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dudek
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Langley
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Zampetaki
authors.affiliation: Biomedical Research Centre, King's College London, UK.
authors.forename: Emanuele
authors.initials: E
authors.lastname: de Rinaldis
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, UK.
authors.forename: Shu
authors.initials: S
authors.lastname: Ye
authors.affiliation: William Harvey Research Institute, Queen Mary University of London, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Warner
authors.affiliation: Biomedical Research Centre, King's College London, UK.
authors.forename: Alka
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Department of Neurology, Medical University Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, UK.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.affiliation: King's British Heart Foundation Centre, King's College London, UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010979:Platelet Function Tests; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: C527111:MIRN126 microRNA, human; C545201:MIRN126 microRNA, mouse; D035683:MicroRNAs; D009841:Oligonucleotides; D010975:Platelet Aggregation Inhibitors
keywords: acute coronary syndrome; biomarkers; blood platelet; micro-RNAs; polymorphism, single nucleotide