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Article

Comprehensive Characterization of Platelet-Enriched MicroRNAs as Biomarkers of Platelet Activation

1
TAmiRNA GmbH, 1110 Vienna, Austria
2
Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraße 17, 1090 Vienna, Austria
3
AdvanceCOR GmbH, Fraunhoferstr. 9a, D-82152 Martinsried, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Miron Sopić, Constanza Emanueli, Susana Novella and Rajesh Katare
Cells 2022, 11(8), 1254; https://doi.org/10.3390/cells11081254
Received: 7 February 2022 / Revised: 18 March 2022 / Accepted: 23 March 2022 / Published: 7 April 2022
(This article belongs to the Special Issue Non Coding RNA in Cardiovascular Biology and Medicine)
Dysregulation of platelet function is causally connected to thrombus formation and cardiovascular diseases. Therefore, assessing platelet reactivity is crucial. However, current platelet function tests come with pitfalls, limiting clinical use. Plasma miRNA signatures have been suggested as novel biomarkers for predicting/diagnosing cardiovascular diseases and monitoring antiplatelet therapy. Here, we provide results from a comprehensive study on the feasibility of using circulatory platelet miRNAs as surrogate markers of platelet activation. We performed small RNA-Seq on different blood cell types to confirm known and identify novel platelet-enriched miRNAs and validated a panel of 16 miRNAs using RT-qPCR. To identify the main carrier of these blood-based platelet miRNAs, we enriched and analyzed distinct microvesicle populations. Platelets were stimulated with GPVI and P2Y12 agonists in vitro to monitor the release of the selected miRNAs following activation. Finally, the miRNA panel was also measured in plasma from mice undergoing the Folts intervention (recurrent thrombus formation in the carotid artery). Applying an unbiased bioinformatics-supported workflow to our NGS data, we were able to confirm a panel of previously established miRNA biomarker candidates and identify three new candidates (i.e., miR-199a-3p, miR-151a-5p, and miR-148b-3p). Basal levels of platelet-derived miRNAs in plasma were mainly complexed with proteins, not extracellular vesicles. We show that changes in miRNA levels due to platelet activation are detectable using RT-qPCR. In addition, we highlight limitations of studying the in vitro release of miRNAs from platelets. In vivo thrombosis resulted in significant elevations of platelet-derived miRNA levels in mice. In conclusion, we provide in-depth evidence that activated platelets release miRNAs, resulting in measurable changes in circulatory miRNA levels, rendering them promising biomarker candidates. View Full-Text
Keywords: platelet-enriched miRNAs; microRNA; biomarker; antiplatelet therapy; platelet activation; microvesicles; plasma miRNAs; thrombomiRs platelet-enriched miRNAs; microRNA; biomarker; antiplatelet therapy; platelet activation; microvesicles; plasma miRNAs; thrombomiRs
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MDPI and ACS Style

Krammer, T.L.; Zeibig, S.; Schrottmaier, W.C.; Pirabe, A.; Goebel, S.; Diendorfer, A.B.; Holthoff, H.-P.; Assinger, A.; Hackl, M. Comprehensive Characterization of Platelet-Enriched MicroRNAs as Biomarkers of Platelet Activation. Cells 2022, 11, 1254. https://doi.org/10.3390/cells11081254

AMA Style

Krammer TL, Zeibig S, Schrottmaier WC, Pirabe A, Goebel S, Diendorfer AB, Holthoff H-P, Assinger A, Hackl M. Comprehensive Characterization of Platelet-Enriched MicroRNAs as Biomarkers of Platelet Activation. Cells. 2022; 11(8):1254. https://doi.org/10.3390/cells11081254

Chicago/Turabian Style

Krammer, Teresa L., Stephan Zeibig, Waltraud C. Schrottmaier, Anita Pirabe, Silvia Goebel, Andreas B. Diendorfer, Hans-Peter Holthoff, Alice Assinger, and Matthias Hackl. 2022. "Comprehensive Characterization of Platelet-Enriched MicroRNAs as Biomarkers of Platelet Activation" Cells 11, no. 8: 1254. https://doi.org/10.3390/cells11081254

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