12-hydroxyeicosatetraenoic acid is associated with variability in aspirin-induced platelet inhibition

Journal of Inflammation

Research

Stephen J Leslie¹  Phillip D Whitfield²  Matthew H Law²  Jun Wei²  Ian L Megson²  Andrew T Treweeke²  Benjamin H Maskrey²  Gordon F Rushworth³ 

[1] Cardiac Unit, Raigmore Hospital, Inverness, UK;Department of Diabetes and Cardiovascular Science, University of the Highlands and Islands, Old Perth Road, IV2 3JH, Inverness, UK;Highland Clinical Research Facility, Inverness, UK;

关键词: Aspirin;    Platelet;    12-HETE;    Thromboxane;    Eicosanoids;    Anti-inflammatory;   

DOI  :  10.1186/s12950-014-0033-4

 received in 2014-08-19, accepted in 2014-10-08,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundAspirin is one of the most widely used non-steroidal anti-inflammatory drugs (NSAIDs). It is also a commonly used anti-platelet drug, which inhibits the formation of the platelet activator, thromboxane A2 (TxA2) via inhibition of cyclooxygenase-1 (COX-1). However, the presence of a patient subset that fails to respond to aspirin despite reduced TxA2 concentrations suggests that the effect of aspirin might be more complex than exclusive COX-1 inhibition.MethodsIn this study we evaluated the impact of in vivo oral administration of a standard anti-platelet dose (75 mg) of aspirin in healthy volunteers on the acute impact of in vitro collagen-mediated platelet aggregation and generation of platelet-derived TxA2 and the 12-lipoxygenase (LOX) metabolite 12-hydroxyeicosatetraenoic acid (12-HETE). The eicosanoids were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS).ResultsLow-dose aspirin administration not only inhibited TxA2 generation but also decreased the production of 12-HETE. Furthermore, a significant correlation was observed between the levels of 12-HETE and collagen-induced platelet aggregation. Pre-treatment of platelets with the 12-LOX inhibitor, baicalein, prior to activation attenuated platelet aggregation.ConclusionsThese findings support a role for 12-HETE as a pro-aggregatory eicosanoid in platelet function and suggest a role for 12-HETE in variable sensitivity to aspirin. The study also highlights a potentially important mechanism by which aspirin impacts upon eicosanoid generation.

【 授权许可】

Unknown   
© Maskrey et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.