Aspirin triggers anti inflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial
Aspirin triggers anti inflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial
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DOI：
10.1073/pnas.0405445101
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发表时间：
2004-10-19
影响因子：
11.1
通讯作者：
Serhan, CN
中科院分区：
文献类型：
--
作者：
Chiang, N;Bermudez, EA;Serhan, CN
越来越多的证据表明，阿司匹林通过内皮细胞和白细胞之间的相互作用来启动新型抗炎介质的生物合成。这些介质被归类为阿司匹林触发的15-表脂蛋白。这些化合物可能至少在一定程度上解释了阿司匹林的临床益处，这些益处有别于阿司匹林作为血小板抑制剂的广为人知的作用。在这里，我们讨论了在人类中，阿司匹林触发的15-表泊沙星A(4)(ATL)的形成是否依赖于阿司匹林，以及它与阿司匹林抗血小板活性的关系。我们在128名健康受试者中进行了一项随机临床试验，这些受试者被分配给安慰剂或每天服用81、325或650毫克阿司匹林，为期8周。从基线和8周采集的血液中评估血浆血栓素(TX)B-2和ATL，这是一种反映血小板反应性的指标。81 mg阿司匹林组血浆ATL水平显著升高(0.25+/-0.63 ng/ml，P=0.04)，325 mg组接近升高(0.16+/-0.71 ng/ml)，650 mg组无明显变化(0.01+/-0.75 ng/ml，P=0.96)。当ATL和TXB2被比较时，在所有三种剂量的阿司匹林中，水平都以统计学上显著且相反的方向变化(P<；0.01)。这些结果表明，小剂量阿司匹林(每天81毫克)可启动抗炎ATL的产生，与TX的抑制相反。监测ATL可能是一项简单的临床参数，可以用来验证小剂量阿司匹林治疗后个体的血管白细胞抗炎反应。这些结果也强调了细胞间相互作用在调节止血、血栓和炎症过程中的重要性。
There 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.