Circulating MicroRNAs and Monocyte-Platelet Aggregate Formation in Acute Coronary Syndrome

Thromb Haemost. 2021 Jul;121(7):913-922. doi: 10.1055/s-0040-1722226. Epub 2021 Jan 14.

Abstract

Background: Monocyte-platelet aggregates (MPAs) are a sensitive marker of in vivo platelet activation in acute coronary syndrome (ACS) and associated with clinical outcomes. MicroRNAs (miRs) play an important role in the regulation of platelet activation, and may influence MPA formation. Both, miRs and MPA, could be influenced by the type of P2Y12 inhibitor.

Aim: To study the association of platelet-related miRs with MPA formation in ACS patients on dual antiplatelet therapy (DAPT), and to compare miRs and MPA levels between prasugrel- and ticagrelor-treated patients.

Methods and results: We analyzed 10 circulating platelet-related miRs in 160 consecutive ACS patients on DAPT with low-dose aspirin and either prasugrel (n = 80) or ticagrelor (n = 80). MPA formation was measured by flow cytometry without addition of platelet agonists and after simulation with the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, adenosine diphosphate (ADP), or arachidonic acid (AA). In multivariate regression analyses, we identified miR-21 (β = 9.50, 95% confidence interval [CI]: 1.60-17.40, p = 0.019) and miR-126 (β = 7.50, 95% CI: 0.55-14.44, p = 0.035) as independent predictors of increased MPA formation in vivo and after TLR-1/2 stimulation. In contrast, none of the investigated miRs was independently associated with MPA formation after stimulation with ADP or AA. Platelet-related miR expression and MPA formation did not differ significantly between prasugrel- and ticagrelor-treated patients.

Conclusion: Platelet-related miR-21 and miR-126 are associated with MPA formation in ACS patients on DAPT. miRs and MPA levels were similar in prasugrel- and ticagrelor-treated patients.

Publication types

  • Observational Study

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / therapy*
  • Aged
  • Aspirin / pharmacology*
  • Blood Platelets / cytology*
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Monocytes / cytology*
  • Platelet Activation
  • Platelet Aggregation Inhibitors / pharmacology
  • Prasugrel Hydrochloride / pharmacology*
  • Purinergic P2Y Receptor Antagonists / pharmacology*
  • Receptors, Purinergic P2Y12 / chemistry*
  • Ticagrelor / pharmacology*

Substances

  • MIRN126 microRNA, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Aspirin