Association of MicroRNAs and YRNAs with Platelet Function
Rationale: Platelets shed microRNAs (miRNAs). Plasma miRNAs change upon platelet inhibition. It is unclear if 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 two peaks at 22-23 and 32-33 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 ACS 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 ACS patients on different anti-platelet 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), 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 ACS patients and platelet activation markers in the general population. Alterations in miR-126 affect platelet reactivity.
- Received December 31, 2014.
- Revision received December 1, 2015.
- Accepted December 8, 2015.