Circulating microRNAs as biomarkers and mediators of platelet activation

Abstract

Platelets are essential mediators of physiological hemostasis and pathological thrombosis. Currently available tests and markers of platelet activation did not prove successful in guiding treatment decisions for patients with cardiovascular disease, justifying further research into novel markers of platelet reactivity. Platelets contain a variety of microRNAs (miRNAs) and are a major contributor to the extracellular circulating miRNA pool. Levels of platelet-derived miRNAs in the circulation have been associated with different measures of platelet activation as well as antiplatelet therapy and have therefore been implied as potential new markers of platelet reactivity. In contrast to the ex vivo assessment of platelet reactivity by current platelet function tests, miRNA measurements may enable assessment of platelet reactivity in vivo. It remains to be seen however, whether miRNAs may aid clinical diagnostics. Major limitations in the platelet miRNA research field remain the susceptibility to preanalytical variation, non-standardized sample preparation and data normalization that hampers inter-study comparisons. In this review, we provide an overview of the literature on circulating miRNAs as biomarkers of platelet activation, highlighting the underlying biology, the application in patients with cardiovascular disease and antiplatelet therapy and elaborating on technical limitations regarding their quantification in the circulation.

Keywords:

• Biomarker
• cardiovascular disease
• microRNA
• noncoding RNA
• platelets
• thrombosis

Acknowledgements

M.M. acknowledges support as part of the Transcampus TU Dresden King’s College London Initiative. Figures were created with Biorender.com.

Disclosure statement

M.M. has filed and licenced patent applications on miRNAs as platelet biomarkers.

Additional information

Funding

C.G. is funded by a BHF PhD studentship [FS/18/60/34181]. M.M. is a British Heart Foundation (BHF) Chair Holder with BHF program grant support [CH/16/3/32406, RG/16/14/32397]. M.M.’s research is made possible through the support of the BIRAX Ageing Initiative and funding from the EU Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 813716 (TRAIN-HEART), the Leducq Foundation [18CVD02], the excellence initiative VASCage [Centre for Promoting Vascular Health in the Ageing Community, project number 868624] of the Austrian Research Promotion Agency FFG (COMET program–Competence Centers for Excellent Technologies) funded by the Austrian Ministry for Transport, Innovation and Technology; the Austrian Ministry for Digital and Economic Affairs; and the federal states Tyrol (via Standortagentur), Salzburg and Vienna (via Vienna Business Agency), two BHF project grant supports [PG/17/48/32956, SP/17/10/33219] and the BHF Centre for Vascular Regeneration with Edinburgh/Bristol [RM/17/3/33381].