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Circ Res. 2016 Feb 5;118(3):420-432. doi: 10.1161/CIRCRESAHA.114.305663. Epub 2015 Dec 8.

Association of MicroRNAs and YRNAs With Platelet Function.

Author information

1
King's British Heart Foundation Centre, King's College London, UK.
2
Department of Public Health and Primary Care, University of Cambridge, UK.
3
Department of Neurology, Medical University Innsbruck, Austria.
4
Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
5
William Harvey Research Institute, Queen Mary University of London, UK.
6
Biomedical Research Centre, King's College London, UK.
7
Department of Cardiovascular Sciences, University of Leicester, UK.
8
Department of Cardiovascular Science, University of Sheffield, UK.
#
Contributed equally

Abstract

RATIONALE:

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.

METHODS AND 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.

KEYWORDS:

acute coronary syndrome; biomarkers; blood platelet; micro-RNAs; polymorphism, single nucleotide

PMID:
26646931
PMCID:
PMC5065093
DOI:
10.1161/CIRCRESAHA.114.305663
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

King’s College London filed and licensed patent applications related to circulating miRNAs as biomarkers. R.F.S. reports receiving research grants, honoraria and/or consultancy fees from AstraZeneca, Aspen, ThermoFisher Scientific, Eli Lilly/Daiichi Sankyo, Merck, Accumetrics, Novartis, Correvio, PlaqueTec, Sanofi-Aventis, Medscape, Regeneron, Roche and The Medicines Company.

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