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

Journal of Inflammation

Phillip D Whitfield³  Ian L Megson³  Stephen J Leslie¹  Jun Wei³  Andrew T Treweeke³  Matthew H Law³  Gordon F Rushworth²  Benjamin H Maskrey³ 

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

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

Others  :  1140762
DOI  :  10.1186/s12950-014-0033-4

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

【 摘 要 】

Background

Aspirin 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.

Methods

In 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).

Results

Low-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.

Conclusions

These 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】

   
2014 Maskrey et al.; licensee BioMed Central Ltd.

【 图 表 】

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