Dietary intake of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) results in cardioprotective benefits. However, the cellular and physiological bases for these benefits remain unclear. We hypothesized that EPA and DHA treatments would interfere with collagen-mediated platelet signaling. Thirty healthy volunteers received 28 days of 3.4 g/d EPA+DHA with and without a single dose of aspirin. Clinical hematologic parameters were then measured along with assays of collagen-stimulated platelet activation and protein phosphorylation. Omega-3 therapy led to a small but significant reduction in platelets (6.3%) and red blood cells (1.7%), but did not impair clinical time-to-closure assays. However, collagen-mediated platelet signaling events of integrin activation, α-granule secretion, and phosphatidylserine exposure were all reduced by roughly 50% after omega-3 incorporation, and collagen-induced tyrosine phosphorylation was significantly impaired. The diminished platelet response to collagen may account for some of the cardioprotective benefits provided by DHA and EPA.
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