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DHA 12- LOX- derived oxylipins regulate platelet activation and thrombus formation through a PKA- dependent signaling pathway
dc.contributor.authorYamaguchi, Adriana
dc.contributor.authorStanger, Livia
dc.contributor.authorFreedman, Cody J.
dc.contributor.authorStandley, Melissa
dc.contributor.authorHoang, Timothy
dc.contributor.authorAdili, Reheman
dc.contributor.authorTsai, Wan‐chen
dc.contributor.authorHoorebeke, Christopher
dc.contributor.authorHolman, Theodore R.
dc.contributor.authorHolinstat, Michael
dc.date.accessioned2021-04-06T02:09:51Z
dc.date.available2022-04-05 22:09:49en
dc.date.available2021-04-06T02:09:51Z
dc.date.issued2021-03
dc.identifier.citationYamaguchi, Adriana; Stanger, Livia; Freedman, Cody J.; Standley, Melissa; Hoang, Timothy; Adili, Reheman; Tsai, Wan‐chen ; Hoorebeke, Christopher; Holman, Theodore R.; Holinstat, Michael (2021). "DHA 12- LOX- derived oxylipins regulate platelet activation and thrombus formation through a PKA- dependent signaling pathway." Journal of Thrombosis and Haemostasis (3): 839-851.
dc.identifier.issn1538-7933
dc.identifier.issn1538-7836
dc.identifier.urihttps://hdl.handle.net/2027.42/167023
dc.description.abstractBackgroundThe effects of docosahexaenoic acid (DHA) on cardiovascular disease are controversial and a mechanistic understanding of how this omega- 3 polyunsaturated fatty acid (Ï - 3 PUFA) regulates platelet reactivity and the subsequent risk of a thrombotic event is warranted. In platelets, DHA is oxidized by 12- lipoxygenase (12- LOX) producing the oxidized lipids (oxylipins) 11- HDHA and 14- HDHA. We hypothesized that 12- LOX DHA- oxylipins may be involved in the beneficial effects observed in dietary supplemental treatment with Ï - 3 PUFAs or DHA itself.ObjectivesTo determine the effects of DHA, 11- HDHA, and 14- HDHA on platelet function and thrombus formation, and to elucidate the mechanism by which these Ï - 3 PUFAs regulate platelet activation.Methods and resultsDHA, 11- HDHA, and 14- HDHA attenuated collagen- induced human platelet aggregation, but only the oxylipins inhibited - ºIIbβ3 activation and decreased - º- granule secretion. Furthermore, treatment of whole blood with DHA and its oxylipins impaired platelet adhesion and accumulation to a collagen- coated surface. Interestingly, thrombus formation was only diminished in mice treated with 11- HDHA or 14- HDHA, and mouse platelet activation was inhibited following acute treatment with these oxylipins or chronic treatment with DHA, suggesting that under physiologic conditions, the effects of DHA are mediated through its oxylipins. Finally, the protective mechanism of DHA oxylipins was shown to be mediated via activation of protein kinase A.ConclusionsThis study provides the first mechanistic evidence of how DHA and its 12- LOX oxylipins inhibit platelet activity and thrombus formation. These findings support the beneficial effects of DHA as therapeutic intervention in atherothrombotic diseases.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherplatelet
dc.subject.otherthrombosis
dc.subject.otherdocosahexaenoic acid
dc.subject.other12- lipoxygenase
dc.subject.otheromega- 3 polyunsaturated fatty acids
dc.titleDHA 12- LOX- derived oxylipins regulate platelet activation and thrombus formation through a PKA- dependent signaling pathway
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelInternal Medicine and Specialties
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/167023/1/jth15184-sup-0001-Supinfo.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/167023/2/jth15184.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/167023/3/jth15184_am.pdf
dc.identifier.doi10.1111/jth.15184
dc.identifier.sourceJournal of Thrombosis and Haemostasis
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