418 The antiplatelet effects of EPA, an omega-3 fatty acid, are mediated by its 12-lipoxygenase metabolite, 12-HEPE
OBJECTIVES/GOALS: To determine whether cardioprotective effects observed in individuals taking dietary supplementation with eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid, are realized by altering platelet function, and if these effects are mediated through the 12-lipoxygenase derive...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2024-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866124003625/type/journal_article |
| _version_ | 1827296117222539264 |
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| author | Krista Goerger Taekyu Lee Devin Gilmore Michelle Tran Theodore R. Holman Michael Holinstat |
| author_facet | Krista Goerger Taekyu Lee Devin Gilmore Michelle Tran Theodore R. Holman Michael Holinstat |
| author_sort | Krista Goerger |
| collection | DOAJ |
| description | OBJECTIVES/GOALS: To determine whether cardioprotective effects observed in individuals taking dietary supplementation with eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid, are realized by altering platelet function, and if these effects are mediated through the 12-lipoxygenase derived metabolite, 12-hydroxyeicosapentaenoic acid (12-HEPE). METHODS/STUDY POPULATION: Washed platelets or platelet rich plasma from healthy human donors were treated with EPA and 12-HEPE to assess their ability to inhibit platelet activation. Platelets were stimulated with agonists targeting different steps of the hemostatic response to vascular injury. Platelet aggregation, dense granule secretion, surface expression of integrin αIIbβ3 and P-selectin, and clot retraction were analyzed. To assess signaling through Gαs-GPCRs and protein kinase A activity, phosphorylation of vasodilator-stimulated phosphoprotein (VASP) was examined via western blot following treatment with EPA or 12-HEPE. RESULTS/ANTICIPATED RESULTS: EPA and 12-HEPE dose-dependently inhibit both collagen and thrombin-induced platelet aggregation. Furthermore, 12-HEPE more potently attenuates dense granule secretion and surface expression of platelet activation markers, integrin αIIbβ3 and P-selectin, in comparison to EPA. Plasma treated with EPA delayed thrombin-induced clot retraction, while 12-HEPE had no effect. Additionally, treatment with 12-HEPE increases phosphorylation of VASP, suggesting it could signal through the activation of the eicosanoid Gαs-GPCRs. DISCUSSION/SIGNIFICANCE: Here, we show for the first time that EPA directly inhibits platelet activation through its 12-LOX metabolite, 12-HEPE. These findings provide further insight into the mechanisms underlying the cardioprotective effects of EPA. A better understanding of current PUFA supplementations can inform treatment and prevention of cardiovascular diseases. |
| first_indexed | 2024-04-24T14:32:23Z |
| format | Article |
| id | doaj.art-c467527b551f4b9691d722308df0cb8c |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-24T14:32:23Z |
| publishDate | 2024-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-c467527b551f4b9691d722308df0cb8c2024-04-03T02:00:11ZengCambridge University PressJournal of Clinical and Translational Science2059-86612024-04-01812412510.1017/cts.2024.362418 The antiplatelet effects of EPA, an omega-3 fatty acid, are mediated by its 12-lipoxygenase metabolite, 12-HEPEKrista Goerger0Taekyu Lee1Devin Gilmore2Michelle Tran3Theodore R. Holman4Michael Holinstat5University of MichiganUniversity of MichiganUniversity of MichiganUniversity of California Santa CruzUniversity of California Santa CruzUniversity of MichiganOBJECTIVES/GOALS: To determine whether cardioprotective effects observed in individuals taking dietary supplementation with eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid, are realized by altering platelet function, and if these effects are mediated through the 12-lipoxygenase derived metabolite, 12-hydroxyeicosapentaenoic acid (12-HEPE). METHODS/STUDY POPULATION: Washed platelets or platelet rich plasma from healthy human donors were treated with EPA and 12-HEPE to assess their ability to inhibit platelet activation. Platelets were stimulated with agonists targeting different steps of the hemostatic response to vascular injury. Platelet aggregation, dense granule secretion, surface expression of integrin αIIbβ3 and P-selectin, and clot retraction were analyzed. To assess signaling through Gαs-GPCRs and protein kinase A activity, phosphorylation of vasodilator-stimulated phosphoprotein (VASP) was examined via western blot following treatment with EPA or 12-HEPE. RESULTS/ANTICIPATED RESULTS: EPA and 12-HEPE dose-dependently inhibit both collagen and thrombin-induced platelet aggregation. Furthermore, 12-HEPE more potently attenuates dense granule secretion and surface expression of platelet activation markers, integrin αIIbβ3 and P-selectin, in comparison to EPA. Plasma treated with EPA delayed thrombin-induced clot retraction, while 12-HEPE had no effect. Additionally, treatment with 12-HEPE increases phosphorylation of VASP, suggesting it could signal through the activation of the eicosanoid Gαs-GPCRs. DISCUSSION/SIGNIFICANCE: Here, we show for the first time that EPA directly inhibits platelet activation through its 12-LOX metabolite, 12-HEPE. These findings provide further insight into the mechanisms underlying the cardioprotective effects of EPA. A better understanding of current PUFA supplementations can inform treatment and prevention of cardiovascular diseases.https://www.cambridge.org/core/product/identifier/S2059866124003625/type/journal_article |
| spellingShingle | Krista Goerger Taekyu Lee Devin Gilmore Michelle Tran Theodore R. Holman Michael Holinstat 418 The antiplatelet effects of EPA, an omega-3 fatty acid, are mediated by its 12-lipoxygenase metabolite, 12-HEPE Journal of Clinical and Translational Science |
| title | 418 The antiplatelet effects of EPA, an omega-3 fatty acid, are mediated by its 12-lipoxygenase metabolite, 12-HEPE |
| title_full | 418 The antiplatelet effects of EPA, an omega-3 fatty acid, are mediated by its 12-lipoxygenase metabolite, 12-HEPE |
| title_fullStr | 418 The antiplatelet effects of EPA, an omega-3 fatty acid, are mediated by its 12-lipoxygenase metabolite, 12-HEPE |
| title_full_unstemmed | 418 The antiplatelet effects of EPA, an omega-3 fatty acid, are mediated by its 12-lipoxygenase metabolite, 12-HEPE |
| title_short | 418 The antiplatelet effects of EPA, an omega-3 fatty acid, are mediated by its 12-lipoxygenase metabolite, 12-HEPE |
| title_sort | 418 the antiplatelet effects of epa an omega 3 fatty acid are mediated by its 12 lipoxygenase metabolite 12 hepe |
| url | https://www.cambridge.org/core/product/identifier/S2059866124003625/type/journal_article |
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