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

Stefan Stojkovic; Patricia P. Wadowski; Patrick Haider; Constantin Weikert; Joseph Pultar; Silvia Lee; Beate Eichelberger; Christian Hengstenberg; Johann Wojta; Simon Panzer; Svitlana Demyanets; Thomas Gremmel

doi:10.1055/s-0040-1722226

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Patricia P. Wadowski

¹Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Patrick Haider

¹Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Constantin Weikert

¹Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Joseph Pultar

¹Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Silvia Lee

¹Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Beate Eichelberger

²Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria

,

Christian Hengstenberg

¹Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Johann Wojta

¹Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

³Core Facilities, Medical University of Vienna, Vienna, Austria

⁴Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria

,

Simon Panzer

²Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria

,

Svitlana Demyanets

⁵Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

,

Thomas Gremmel

¹Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

⁶Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria

› Author Affiliations

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.

Keywords

microRNAs - monocyte–platelet aggregates - platelet activation - ACS - DAPT

Full Text

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Supplementary Material