Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.
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Ellero-Simatos S, Lewis JP, Georgiades A, Yerges-Armstrong LM, Beitelshees AL, Horenstein RB, Dane A, Harms AC, Ramaker R, Vreeken RJ, Perry CG, Zhu H, Sanchez CL, Kuhn C, Ortel TL, Shuldiner AR, Hankemeier T, Kaddurah-Daouk R
Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.
CPT Pharmacometrics Syst Pharmacol. 2014 Jul 16;3:e125. doi: 10.1038/psp.2014.22.
- PubMed ID
- 25029353 [ View in PubMed]
- Abstract
While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent of response (15/34 metabolites changed). In our discovery (N = 80) and replication (N = 125) cohorts, higher serotonin levels pre- and postaspirin correlated with high, postaspirin, collagen-induced platelet aggregation. In a third cohort, platelets from subjects with the highest levels of serotonin preaspirin retained higher reactivity after incubation with aspirin than platelets from subjects with the lowest serotonin levels preaspirin (72 +/- 8 vs. 61 +/- 11%, P = 0.02, N = 20). Finally, ex vivo, serotonin strongly increased platelet reactivity after platelet incubation with aspirin (+20%, P = 4.9 x 10(-4), N = 12). These results suggest that serotonin is implicated in aspirin response variability.
DrugBank Data that Cites this Article
- Pharmaco-metabolomics
Drug Drug Groups Metabolite Change Description Acetylsalicylic acid Approved Vet Approved Glycylglycine decreased Acetylsalicylic acid decreases the level of Glycylglycine in the blood Acetylsalicylic acid Approved Vet Approved L-glutamic acid decreased Acetylsalicylic acid decreases the level of L-glutamic acid in the blood Acetylsalicylic acid Approved Vet Approved L-Leucine decreased Acetylsalicylic acid decreases the level of L-Leucine in the blood Acetylsalicylic acid Approved Vet Approved L-Phenylalanine decreased Acetylsalicylic acid decreases the level of L-Phenylalanine in the blood Acetylsalicylic acid Approved Vet Approved L-Serine decreased Acetylsalicylic acid decreases the level of L-Serine in the blood Acetylsalicylic acid Approved Vet Approved Ethanolamine decreased Acetylsalicylic acid decreases the level of Ethanolamine in the blood Acetylsalicylic acid Approved Vet Approved L-Asparagine decreased Acetylsalicylic acid decreases the level of L-Asparagine in the blood Acetylsalicylic acid Approved Vet Approved L-Valine decreased Acetylsalicylic acid decreases the level of L-Valine in the blood Acetylsalicylic acid Approved Vet Approved Beta-alanine decreased Acetylsalicylic acid decreases the level of Beta-alanine in the blood Acetylsalicylic acid Approved Vet Approved L-Lysine decreased Acetylsalicylic acid decreases the level of L-Lysine in the blood Acetylsalicylic acid Approved Vet Approved L-Histidine decreased Acetylsalicylic acid decreases the level of L-Histidine in the blood Acetylsalicylic acid Approved Vet Approved L-Tyrosine decreased Acetylsalicylic acid decreases the level of L-Tyrosine in the blood Acetylsalicylic acid Approved Vet Approved L-Glutamine decreased Acetylsalicylic acid decreases the level of L-Glutamine in the blood Acetylsalicylic acid Approved Vet Approved O-Phosphoethanolamine increased Acetylsalicylic acid increases the level of O-Phosphoethanolamine in the blood Acetylsalicylic acid Approved Vet Approved Arachidonic acid decreased Acetylsalicylic acid decreases the level of Arachidonic acid in the blood Acetylsalicylic acid Approved Vet Approved Asparagine decreased Acetylsalicylic acid decreases the level of Asparagine in the blood Acetylsalicylic acid Approved Vet Approved Aspartic acid decreased Acetylsalicylic acid decreases the level of Aspartic acid in the blood Acetylsalicylic acid Approved Vet Approved Glutamic acid decreased Acetylsalicylic acid decreases the level of Glutamic acid in the blood Acetylsalicylic acid Approved Vet Approved Histidine decreased Acetylsalicylic acid decreases the level of Histidine in the blood Acetylsalicylic acid Approved Vet Approved Leucine decreased Acetylsalicylic acid decreases the level of Leucine in the blood Acetylsalicylic acid Approved Vet Approved Lysine decreased Acetylsalicylic acid decreases the level of Lysine in the blood Acetylsalicylic acid Approved Vet Approved Phenylalanine decreased Acetylsalicylic acid decreases the level of Phenylalanine in the blood Acetylsalicylic acid Approved Vet Approved Serine decreased Acetylsalicylic acid decreases the level of Serine in the blood Acetylsalicylic acid Approved Vet Approved Valine decreased Acetylsalicylic acid decreases the level of Valine in the blood Acetylsalicylic acid Approved Vet Approved L-Aspartic acid decreased Acetylsalicylic acid decreases the level of L-Aspartic acid in the blood Acetylsalicylic acid Approved Vet Approved Serotonin increased Acetylsalicylic acid increases the level of Serotonin in the blood Acetylsalicylic acid Approved Vet Approved Glycine decreased Acetylsalicylic acid decreases the level of Glycine in the blood Acetylsalicylic acid Approved Vet Approved Taurine decreased Acetylsalicylic acid decreases the level of Taurine in the blood Acetylsalicylic acid Approved Vet Approved Ornithine decreased Acetylsalicylic acid decreases the level of Ornithine in the blood