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Updated: Dec 18, 2025
Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
MicroRNA-126 is a regulator of platelet-supported thrombin generation
Veronika Zapilko1, Richard J Fish2, Alix Garcia1
1Geneva Platelet Group, Faculty of Medicine, University of Geneva , Geneva, Switzerland.
Abstract:
Circulating microRNA (miRNA) expression profiles correlate with platelet reactivity. MiR-126 is a promising candidates in this regard. We generated a transgenic zebrafish line with thrombocyte-specific overexpression of miR-126. Laser injury of the posterior cardinal vein of 5 day-old larvae was performed with or without antithrombotic pre-treatment. Platelet-like structures (PLS) derived from human megakaryocytes transfected with miR-126 were also evaluated for procoagulant activity. Finally, we studied the correlation between miR-126 level and thrombin generation markers in a cohort of stable cardiovascular patients. Control zebrafish developed small thrombocyte-rich thrombi at the site of vessel injury, without vessel occlusion. The miR-126 transgenic line developed an occluding thrombus in 75% (95% CI: 51-91%) of larvae. Pre-treatment with the direct thrombin inhibitor argatroban, but not aspirin, prevented vessel occlusion in the transgenic line (0% occlusion, 95%CI: 0-18%). Upon activation, human PLS showed an increased procoagulant profile after miR-126 transfection compared to control. Finally, the plasma levels of miR-126, but not a control platelet-derived miRNA, correlated with markers of in vivo thrombin generation in a cohort of 185 cardiovascular patients. Our results from three complementary approaches support a key role for miR-126 in platelet-supported thrombin generation and open new avenues in the tailoring of antithrombotic treatment.
Insights
MicroRNA-126 (miR-126) promotes platelet reactivity and thrombin generation. Targeting miR-126 may offer new antithrombotic strategies for cardiovascular patients.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Hemostasis and Thrombosis
Background:
- Circulating microRNA (miRNA) profiles are linked to platelet reactivity.
- miR-126 is a key miRNA implicated in platelet function.
Purpose of the Study:
- To investigate the role of miR-126 in platelet-supported thrombin generation.
- To explore the potential of miR-126 as a therapeutic target for antithrombotic treatments.
Main Methods:
- Generated a transgenic zebrafish model overexpressing miR-126 in thrombocytes.
- Assessed thrombus formation and occlusion following laser-induced vessel injury.
- Evaluated procoagulant activity of human platelet-like structures (PLS) transfected with miR-126.
- Correlated plasma miR-126 levels with thrombin generation markers in cardiovascular patients.
Main Results:
- Zebrafish overexpressing miR-126 exhibited occluding thrombi, unlike controls.
- Argatroban, a direct thrombin inhibitor, prevented occlusion in miR-126 transgenic zebrafish, while aspirin did not.
- Human PLS with miR-126 showed enhanced procoagulant activity.
- Plasma miR-126 levels correlated with in vivo thrombin generation markers in cardiovascular patients.
Conclusions:
- miR-126 plays a significant role in platelet-mediated thrombin generation.
- These findings suggest miR-126 as a potential target for novel antithrombotic therapies.
