The effect of EPA and DHA on platelets treated with multiple agonists found in the thrombus core (671.3)

Abstract

The omega‐3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been consistently associated with reduced platelet function, and more recently, with impaired thrombin generation. However, almost all studies to date have focused on how EPA and DHA alter platelet physiology in response to monotypic agonist stimulation. This reductionist approach does not recapitulate the complex chemical environment found in a developing thrombus. Therefore, we asked if platelets treated with multiple agonists like those found in the thrombus core would also display EPA and DHA‐mediated inhibition. We found that optical aggregometry and dense granule secretion was diminished after EPA and DHA incorporation in platelets stimulated with the core clot agonists. We also noted a reduction in both the protein content of platelet lipid rafts and thrombin generation after core agonist stimulation, consistent with our earlier observations. Transmission electron micrographic imaging also established that EPA and DHA‐treated platelets showed moderate ultrastructural malformations after core agonist treatment. These results all suggest that EPA and DHA can abrogate platelet signaling responses within the core of a developing thrombus, further illustrating the potential health benefits of increased EPA and DHA intake.Grant Funding Source: Supported by an Institutional Development Award (IDeA) from the NIH/NIGMS, #P20GM103443