Open AccessOxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study
Author(s) -
ElleroSimatos Sandrine,
Beitelshees Amber L.,
Lewis Joshua P.,
YergesArmstrong Laura M.,
Georgiades Anastasia,
Dane Adrie,
Harms Amy C.,
Strassburg Katrin,
Guled Faisa,
Hendriks Margriet M. W. B.,
Horenstein Richard B.,
Shuldiner Alan R.,
Hankemeier Thomas,
KaddurahDaouk Rima
Publication year - 2015
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.115.002203
Subject(s) - aspirin , medicine , metabolomics , metabolome , platelet , arachidonic acid , pharmacology , in vivo , ex vivo , metabolite , linoleic acid , drug , platelet activation , endocrinology , biochemistry , bioinformatics , chemistry , fatty acid , enzyme , biology , microbiology and biotechnology
Background While aspirin is a well‐established and generally effective anti‐platelet agent, considerable inter‐individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. Methods and Results We used a mass‐spectrometry‐based metabolomics platform to investigate the changes in the serum oxylipid metabolome induced by an aspirin intervention (14 days, 81 mg/day) in healthy subjects (n=156). We observed a global decrease in serum oxylipids in response to aspirin (25 metabolites decreased out of 30 measured) regardless of sex. This decrease was concomitant with a significant decrease in serum linoleic acid levels (−19%, P =1.3×10 −5 ), one of the main precursors for oxylipid synthesis. Interestingly, several linoleic acid‐derived oxylipids were not significantly associated with arachidonic‐induced ex vivo platelet aggregation, a widely accepted marker of aspirin response, but were significantly correlated with platelet reactivity in response to collagen. Conclusions Together, these results suggest that linoleic acid‐derived oxylipids may contribute to the non‐ COX 1 mediated variability in response to aspirin. Pharmacometabolomics allowed for more comprehensive interrogation of mechanisms of action of low dose aspirin and of variation in aspirin response.