12-hydroxyeicosatetraenoic acid is associated with variability in aspirin-induced platelet inhibition

Background: aspirin is one of the most widely used non-steroidal anti-inflammatory drugs (nsaids). it is also a commonly used anti-platelet drug,which inhibits the formation of the platelet activator,thromboxane a2 (txa2) via inhibition of cyclooxygenase-1 (cox-1). however,the presence of a patient subset that fails to respond to aspirin despite reduced txa2 concentrations suggests that the effect of aspirin might be more complex than exclusive cox-1 inhibition. methods: in this study we evaluated the impact of in vivo oral administration of a standard anti-platelet dose (75 mg) of aspirin in healthy volunteers on the acute impact of in vitro collagen-mediated platelet aggregation and generation of platelet-derived txa2 and the 12-lipoxygenase (lox) metabolite 12-hydroxyeicosatetraenoic acid (12-hete). the eicosanoids were quantified using liquid chromatography-tandem mass spectrometry (lc-ms/ms). results: low-dose aspirin administration not only inhibited txa2 generation but also decreased the production of 12-hete. furthermore,a significant correlation was observed between the levels of 12-hete and collagen-induced platelet aggregation. pre-treatment of platelets with the 12-lox inhibitor,baicalein,prior to activation attenuated platelet aggregation. conclusions: these findings support a role for 12-hete as a pro-aggregatory eicosanoid in platelet function and suggest a role for 12-hete in variable sensitivity to aspirin. the study also highlights a potentially important mechanism by which aspirin impacts upon eicosanoid generation. © 2014 maskrey et al.