Nan Chiang1, Shelley Hurwitz, Paul M Ridker, Charles N Serhan. 1. Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Boston, MA, USA.
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 A4. We recently conducted a double-blinded clinical trial with healthy subjects in whom low-doseaspirin (81 mg daily) significantly increased aspirin-triggered 15-epi-lipoxin A4 and concomitantly inhibited thromboxane. Here, we assessed whether plasma aspirin-triggered 15-epi-lipoxin A4 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 B2 and aspirin-triggered 15-epi-lipoxin A4 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 A4(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 A4 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.
RCT Entities:
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 A4. 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 A4 and concomitantly inhibited thromboxane. Here, we assessed whether plasma aspirin-triggered 15-epi-lipoxin A4 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 B2 and aspirin-triggered 15-epi-lipoxin A4 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 A4(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 A4 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.
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