MicroRNA-126 is a regulator of platelet-supported thrombin generation
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 per...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-08-01
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| Series: | Platelets |
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| Online Access: | http://dx.doi.org/10.1080/09537104.2020.1775804 |
| _version_ | 1797684135267926016 |
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| author | Veronika Zapilko Richard J. Fish Alix Garcia Jean-Luc Reny Sylvie Dunoyer-Geindre Thomas Lecompte Marguerite Neerman-Arbez Pierre Fontana |
| author_facet | Veronika Zapilko Richard J. Fish Alix Garcia Jean-Luc Reny Sylvie Dunoyer-Geindre Thomas Lecompte Marguerite Neerman-Arbez Pierre Fontana |
| author_sort | Veronika Zapilko |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:26:13Z |
| format | Article |
| id | doaj.art-634e671b6a69459483384fef854a6f83 |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:26:13Z |
| publishDate | 2020-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-634e671b6a69459483384fef854a6f832023-09-15T10:38:08ZengTaylor & Francis GroupPlatelets0953-71041369-16352020-08-0131674675510.1080/09537104.2020.17758041775804MicroRNA-126 is a regulator of platelet-supported thrombin generationVeronika Zapilko0Richard J. Fish1Alix Garcia2Jean-Luc Reny3Sylvie Dunoyer-Geindre4Thomas Lecompte5Marguerite Neerman-Arbez6Pierre Fontana7University of GenevaUniversity of GenevaUniversity of GenevaUniversity of GenevaUniversity of GenevaUniversity of GenevaUniversity of GenevaUniversity of GenevaCirculating 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.http://dx.doi.org/10.1080/09537104.2020.1775804plateletplatelet reactivitythrombinthrombosiszebrafish |
| spellingShingle | Veronika Zapilko Richard J. Fish Alix Garcia Jean-Luc Reny Sylvie Dunoyer-Geindre Thomas Lecompte Marguerite Neerman-Arbez Pierre Fontana MicroRNA-126 is a regulator of platelet-supported thrombin generation Platelets platelet platelet reactivity thrombin thrombosis zebrafish |
| title | MicroRNA-126 is a regulator of platelet-supported thrombin generation |
| title_full | MicroRNA-126 is a regulator of platelet-supported thrombin generation |
| title_fullStr | MicroRNA-126 is a regulator of platelet-supported thrombin generation |
| title_full_unstemmed | MicroRNA-126 is a regulator of platelet-supported thrombin generation |
| title_short | MicroRNA-126 is a regulator of platelet-supported thrombin generation |
| title_sort | microrna 126 is a regulator of platelet supported thrombin generation |
| topic | platelet platelet reactivity thrombin thrombosis zebrafish |
| url | http://dx.doi.org/10.1080/09537104.2020.1775804 |
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