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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:e14.)
© 2006 American Heart Association, Inc.

Vascular Biology

Aspirin Has A Gender-Dependent Impact on Antiinflammatory 15-Epi-Lipoxin A₄ Formation

A Randomized Human Trial

Nan Chiang; Shelley Hurwitz; Paul M. Ridker; Charles N. Serhan

From the Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine (N.C., C.N.S.), Center for Cardiovascular Disease Prevention and the Donald W. Reynolds Center for Cardiovascular Research (P.M.R.), and Department of Medicine (S.H.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

Reprint requests to Charles N. Serhan, 75 Francis St, Thorn Building for Medical Research, Room 724, Boston, MA 02115. E-mail cnserhan{at}zeus.bwh.harvard.edu

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.

Key Words: leukocyte traffic • inflammation • lipid mediators

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