Aspirin has a gender-dependent impact on antiinflammatory 15-epi-lipoxin A4 formation: a randomized human trial.
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.


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.
Chiang
Nan
N
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Boston, MA, USA.
Hurwitz
Shelley
S
Ridker
Paul M
PM
Serhan
Charles N
CN
D000107:Acetylation; D000328:Adult; D000367:Age Factors; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D006801:Humans; D044045:Lipoxins / Q000096:biosynthesis*; D008875:Middle Aged; D010919:Placebos; D012727:Sex Characteristics; D013929:Thromboxane B2 / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D044045:Lipoxins; D010919:Placebos; C040527:lipoxin A4; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; D001241:Aspirin