Aspirin Has A Gender-Dependent Impact on Antiinflammatory 15-Epi-Lipoxin A 4 Formation

Abstract

Objective— Aspirin blocks thromboxane production that contributes to its well-appreciated antiplatelet action. Aspirin also initiates the biosynthesis of novel antiinflammatory mediators from arachidonic acid, namely aspirin-triggered 15-epi-lipoxin A 4 . We recently conducted a double-blinded clinical trial with healthy subjects in whom low-dose aspirin (81 mg daily) significantly increased aspirin-triggered 15-epi-lipoxin A 4 and concomitantly inhibited thromboxane. Here, we assessed whether plasma aspirin–triggered 15-epi-lipoxin A 4 was age or gender dependent in subjects taking low-dose aspirin. Methods and Results— A total of 128 subjects were allocated to: placebo, 81, 325, or 650 mg daily aspirin for an 8-week period. Plasma thromboxane B 2 and aspirin-triggered 15-epi-lipoxin A 4 were assessed from blood collected at baseline and the conclusion of the trial. We then performed a post-trial analysis in the group receiving low-dose aspirin. In female subjects, we found a positive correlation between age and aspirin-triggered 15-epi-lipoxin A 4 (increase of 0.37 ng/mL per decade), and a negative correlation was observed in men (decrease of 0.29 ng/mL per decade). These trends were significantly different from each other ( P =0.045). Conclusions— Low-dose aspirin has a gender-specific impact on aspirin-triggered 15-epi-lipoxin A 4 production, which may contribute to the gender-dependent clinical benefits of aspirin. Also, they may provide a molecular rationale for low-dose aspirin therapies in elderly women to reduce inflammation-related disorders.