Thromb Haemost 2021; 121(07): 913-922
DOI: 10.1055/s-0040-1722226
Cellular Haemostasis and Platelets

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

Stefan Stojkovic
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Patricia P. Wadowski
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Patrick Haider
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Constantin Weikert
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Joseph Pultar
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Silvia Lee
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Beate Eichelberger
2  Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
,
Christian Hengstenberg
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Johann Wojta
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
3  Core Facilities, Medical University of Vienna, Vienna, Austria
4  Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria
,
Simon Panzer
2  Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
,
Svitlana Demyanets
5  Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
,
Thomas Gremmel
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
6  Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria
› Author Affiliations
Funding The research was funded by the “Medical Scientific Fund of the Mayor of the City of Vienna,” grant number 14016, and by the “Anniversary Fund of the Austrian National Bank,” grant number 16155, to Thomas Gremmel. MicroRNA analysis was performed at TAmiRNA GmbH, Leberstrasse 20, 1110 Vienna, Austria.

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.

Authors' Contributions

T.G., S.S., and S.D. designed the research and wrote the manuscript; P.P.W., C.W., J.P., P.H., and B.E. performed the experiments; S.S. and T.G. analyzed the results; P.P.W., P.H., S.L., S.P., C.W., J.P., B.E., S.D., C.H., and J.W. critically read and revised the manuscript.


Supplementary Material



Publication History

Received: 06 July 2020

Accepted: 18 November 2020

Publication Date:
14 January 2021 (online)

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