An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics
Platelet reactivity (PR), a key pharmacodynamic (PD) component of the action of antiplatelet drugs in cardiovascular disease (CVD) patients, is highly variable. PR is associated with occurrence or recurrence of thrombotic and bleeding events, but this association is modulated by several factors. Con...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/11/5/323 |
| _version_ | 1797536895674089472 |
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| author | Alix Garcia Sylvie Dunoyer-Geindre Séverine Nolli Jean-Luc Reny Pierre Fontana |
| author_facet | Alix Garcia Sylvie Dunoyer-Geindre Séverine Nolli Jean-Luc Reny Pierre Fontana |
| author_sort | Alix Garcia |
| collection | DOAJ |
| description | Platelet reactivity (PR), a key pharmacodynamic (PD) component of the action of antiplatelet drugs in cardiovascular disease (CVD) patients, is highly variable. PR is associated with occurrence or recurrence of thrombotic and bleeding events, but this association is modulated by several factors. Conventional pharmacogenetics explains a minor part of this PR variability, and among determinants of PR, circulating microRNAs (miRNAs) have been the focus of attention during these last years as biomarkers to predict PR and clinical outcomes in CVD. This being said, the impact of miRNAs on platelet function and the mechanisms behind it are largely unknown. The level of a set of candidate miRNAs including miR-126-3p, miR-150-5p, miR-204-5p and miR-223-3p was quantified in plasma samples of stable CVD patients and correlated with PR as assessed by light-transmission aggregometry and in vivo thrombin generation markers. Finally, miRNA target networks were built based on genes involved in platelet function. We show that all candidate miRNAs were associated with platelet aggregation, while only miR-126-3p and miR-223-3p were positively correlated with in vivo thrombin generation markers. In silico analysis identified putative miRNA targets involved in platelet function regulation. Circulating miRNAs were associated with different aspects of platelet reactivity, including platelet aggregation and platelet-supported thrombin generation. This paves the way to a personalized antithrombotic treatment according to miRNA profile in CVD patients. |
| first_indexed | 2024-03-10T12:07:21Z |
| format | Article |
| id | doaj.art-18f92f9bb3c84ffcb6af978102369377 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T12:07:21Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-18f92f9bb3c84ffcb6af9781023693772023-11-21T16:25:51ZengMDPI AGJournal of Personalized Medicine2075-44262021-04-0111532310.3390/jpm11050323An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional PharmacogeneticsAlix Garcia0Sylvie Dunoyer-Geindre1Séverine Nolli2Jean-Luc Reny3Pierre Fontana4Geneva Platelet Group, Faculty of Medicine, University of Geneva, 1205 Geneva, SwitzerlandGeneva Platelet Group, Faculty of Medicine, University of Geneva, 1205 Geneva, SwitzerlandGeneva Platelet Group, Faculty of Medicine, University of Geneva, 1205 Geneva, SwitzerlandGeneva Platelet Group, Faculty of Medicine, University of Geneva, 1205 Geneva, SwitzerlandGeneva Platelet Group, Faculty of Medicine, University of Geneva, 1205 Geneva, SwitzerlandPlatelet reactivity (PR), a key pharmacodynamic (PD) component of the action of antiplatelet drugs in cardiovascular disease (CVD) patients, is highly variable. PR is associated with occurrence or recurrence of thrombotic and bleeding events, but this association is modulated by several factors. Conventional pharmacogenetics explains a minor part of this PR variability, and among determinants of PR, circulating microRNAs (miRNAs) have been the focus of attention during these last years as biomarkers to predict PR and clinical outcomes in CVD. This being said, the impact of miRNAs on platelet function and the mechanisms behind it are largely unknown. The level of a set of candidate miRNAs including miR-126-3p, miR-150-5p, miR-204-5p and miR-223-3p was quantified in plasma samples of stable CVD patients and correlated with PR as assessed by light-transmission aggregometry and in vivo thrombin generation markers. Finally, miRNA target networks were built based on genes involved in platelet function. We show that all candidate miRNAs were associated with platelet aggregation, while only miR-126-3p and miR-223-3p were positively correlated with in vivo thrombin generation markers. In silico analysis identified putative miRNA targets involved in platelet function regulation. Circulating miRNAs were associated with different aspects of platelet reactivity, including platelet aggregation and platelet-supported thrombin generation. This paves the way to a personalized antithrombotic treatment according to miRNA profile in CVD patients.https://www.mdpi.com/2075-4426/11/5/323miRNAbiomarkercardiovascular disordersplatelet aggregationthrombin generation |
| spellingShingle | Alix Garcia Sylvie Dunoyer-Geindre Séverine Nolli Jean-Luc Reny Pierre Fontana An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics Journal of Personalized Medicine miRNA biomarker cardiovascular disorders platelet aggregation thrombin generation |
| title | An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics |
| title_full | An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics |
| title_fullStr | An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics |
| title_full_unstemmed | An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics |
| title_short | An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics |
| title_sort | ex vivo and in silico study providing insights into the interplay of circulating mirnas level platelet reactivity and thrombin generation looking beyond traditional pharmacogenetics |
| topic | miRNA biomarker cardiovascular disorders platelet aggregation thrombin generation |
| url | https://www.mdpi.com/2075-4426/11/5/323 |
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