Circulating microRNA levels indicate platelet and leukocyte activation in endotoxemia despite platelet p2y12 inhibition

Aitana Braza-Boils, Temo Barwari, Clemens Gutmann, Mark R. Thomas, Heather M. Judge, Abhishek Joshi, Raimund Pechlaner, Manu Shankar-Hari, Ramzi A. Ajjan, Ian Sabroe, Robert F. Storey, Manuel Mayr

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15 Citations (Scopus)


There is evidence for the effects of platelet inhibition on innate immune activation. Circulating microRNAs (miRNAs) have been implicated as markers of platelet and leukocyte activation. In the present study, we assessed the effects of P2Y12 inhibitors on platelet and leukocyte miRNAs during endotoxemia. Healthy volunteers were randomly assigned to receive oral ticagrelor (n = 10), clopidogrel (n = 8) or no drug (n = 8) for one week, followed by an intravenous bolus of 2 ng/kg endotoxin. Serum was collected at baseline, after one week of antiplatelet treatment and 6 and 24 h after endotoxin administration. MiRNAs were screened using LNA-based qPCR, followed by TaqMan-qPCR validation of candidates. Clinical validation was performed in 41 sepsis patients. Platelet-enriched miR-197, miR-223 and miR-223* were decreased in volunteers following antiplatelet therapy. Endotoxin increased platelet miRNAs, whilst the opposite effect was seen for leukocyte-enriched miR-150. Neither of these endotoxin-mediated Effects were altered by P2Y12 inhibitors. Sepsis patients with fatal outcomes (n = 12) had reduced miR-150 levels compared with survivors (n = 29). In conclusion, we show that miR-150 is downregulated in experimental endotoxemia and can predict survival in sepsis but is unaffected by P2Y12 inhibition. While P2Y12 inhibition reduces platelet-associated miRNAs in healthy volunteers, it fails to attenuate the response of platelet miRNAs to endotoxemia.

Original languageEnglish
Article number2897
JournalInternational Journal of Molecular Sciences
Issue number8
Publication statusPublished - 2 Apr 2020


  • Antiplatelet therapy
  • Biomarker
  • MicroRNA
  • Sepsis


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