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Novel Characterization of Docohexanoic Acid and Its 12‐LOX Products, 11‐HDHE and 14‐ HDHE on Human Blood Platelets
Author(s) -
Hawley Megan,
Craven Da'Quan Dominique,
Edokobi Nnamdi,
Holman Ted,
Holinstat Michael
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.675.4
Subject(s) - docosahexaenoic acid , polyunsaturated fatty acid , platelet , platelet activation , eicosapentaenoic acid , chemistry , lipoxygenase , arachidonic acid , oxylipin , pharmacology , biochemistry , fish oil , p2y12 , fatty acid , medicine , platelet aggregation , biology , enzyme , fish <actinopterygii> , fishery
Cardiovascular disease (CVD) is currently the leading causes of mortality in the United States in both men and women. Thrombotic‐associated ischemic injuries due to excessive platelet activation are largely responsible for the high level of death associated with CVD. Therapies that seek to pharmacologically inhibit platelet activation, aggregation, or clot stabilization, have the potential to reduce the high mortality rates associated with CVD. Fish oils are currently taken as a cardioprotective supplement, and consist of a mixture of two n‐3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Data elucidating the mechanism by which PUFAs interact with platelets remains controversial. The oxygenated products of PUFAs—oxylipins—have been shown to be critical regulators of platelet function. Our lab recently illustrated the essential role of 12‐lipoxygenase (12‐LOX) in the ability of another PUFA, dihomo‐γ‐linolenic acid (DGLA), to inhibit platelet activation and thrombosis via its oxylipin, 12(S)‐hydroxy‐8Z,10E,14Z‐eicosatrienoic acid (12(S)‐HETrE). Previously, it has been shown that DHA has antiplatelet activity; therefore, we hypothesize that 12‐LOX oxylipins are responsible for the antiplatelet effects of DHA. Our study sought to investigate the role that 12‐LOX derived products of DHA, 11‐ and 14‐ hydroxydocosahexaenoic acid (11‐ and 14‐ HDHE), have on human blood platelet activation. Platelet aggregation, calcium release, granule release, and integrin aIIbb3 activation were measured following agonist stimulation in the presence of 11‐ or 14‐ HDHE. Our data demonstrate that 11‐ or 14‐ HDHE dose‐dependently inhibited aggregation in response to submaximal concentrations of either thrombin or collagen. Additionally, we confirmed that 11‐ or 14‐ HDHE impinged on intracellular signaling as demonstrated by a decrease in Ca2+ mobilization, as well as granule secretion in platelets treated with 11‐ or 14‐ HDHE compared to DMSO treated platelets. Ongoing studies will help to elucidate the mechanism by which DHA and its metabolites inhibit platelet function. Once completed this will be the first study to clearly define a role for DHA and its 12‐LOX metabolites in the regulation of platelet aggregation.