Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial
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CitationChiang, N., E. A. Bermudez, P. M. Ridker, S. Hurwitz, and C. N. Serhan. 2004. “Aspirin Triggers Antiinflammatory 15-Epi-Lipoxin A4 and Inhibits Thromboxane in a Randomized Human Trial.” Proceedings of the National Academy of Sciences 101 (42): 15178–83. https://doi.org/10.1073/pnas.0405445101.
AbstractThere is increasing evidence that aspirin initiates biosynthesis of novel antiinflammatory mediators by means of interactions between endothelial cells and leukocytes. These mediators are classified as aspirin-triggered 15-epi-lipoxins. Such compounds may account at least in part for aspirin's clinical benefits, which are distinct from the well appreciated action of aspirin as a platelet inhibitor. Here, we addressed whether aspirin-triggered 15-epilipoxinA(4) (ATL) formation is aspirin-dependent in humans and its relationship to aspirin's antiplatelet activity. We conducted a randomized clinical trial among 128 healthy subjects allocated to placebo or to 81-,325-, or 650-mg daily doses of aspirin for 8 weeks. Plasma thromboxane (TX)B-2, an indicator of platelet reactivity, and ATL were assessed from blood collected at baseline and at 8 weeks. Plasma ATL levels significantly increased in the 81-mg aspirin group (0.25 +/- 0.63 ng/ml, P = 0.04), with borderline increases in the 325-mg group (0.16 +/- 0.71 ng/ml) and no apparent significant changes in the 650-mg group (0.01 +/- 0.75 ng/ml, P = 0.96). When ATL and TXB2 were compared, levels changed in a statistically significant and opposite direction (P < 0.01) for all three aspirin doses. These results demonstrated that low-dose aspirin (81 mg daily) initiates production of antiinflammatory ATL opposite to the inhibition of TX. Monitoring ATL may represent a simple clinical parameter to verify an individual's vascular leukocyte antiinflammatory response with low-dose aspirin treatment. These results also emphasize the importance of cell-cell interactions in the modulation of hemostatic, thrombotic, and inflammatory processes.
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