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Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.

Publication ,  Journal Article
Ellero-Simatos, S; Lewis, JP; Georgiades, A; Yerges-Armstrong, LM; Beitelshees, AL; Horenstein, RB; Dane, A; Harms, AC; Ramaker, R; Vreeken, RJ ...
Published in: CPT Pharmacometrics Syst Pharmacol
July 16, 2014

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 × 10(-4), N = 12). These results suggest that serotonin is implicated in aspirin response variability.

Duke Scholars

Published In

CPT Pharmacometrics Syst Pharmacol

DOI

ISSN

2163-8306

Publication Date

July 16, 2014

Volume

3

Issue

7

Start / End Page

e125

Location

United States

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3208 Medical physiology
  • 1116 Medical Physiology
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

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Ellero-Simatos, S., Lewis, J. P., Georgiades, A., Yerges-Armstrong, L. M., Beitelshees, A. L., Horenstein, R. B., … Kaddurah-Daouk, R. (2014). Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability. CPT Pharmacometrics Syst Pharmacol, 3(7), e125. https://doi.org/10.1038/psp.2014.22
Ellero-Simatos, S., J. P. Lewis, A. Georgiades, L. M. Yerges-Armstrong, A. L. Beitelshees, R. B. Horenstein, A. Dane, et al. “Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.CPT Pharmacometrics Syst Pharmacol 3, no. 7 (July 16, 2014): e125. https://doi.org/10.1038/psp.2014.22.
Ellero-Simatos S, Lewis JP, Georgiades A, Yerges-Armstrong LM, Beitelshees AL, Horenstein RB, et al. Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability. CPT Pharmacometrics Syst Pharmacol. 2014 Jul 16;3(7):e125.
Ellero-Simatos, S., et al. “Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.CPT Pharmacometrics Syst Pharmacol, vol. 3, no. 7, July 2014, p. e125. Pubmed, doi:10.1038/psp.2014.22.
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, Sànchez 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(7):e125.
Journal cover image

Published In

CPT Pharmacometrics Syst Pharmacol

DOI

ISSN

2163-8306

Publication Date

July 16, 2014

Volume

3

Issue

7

Start / End Page

e125

Location

United States

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3208 Medical physiology
  • 1116 Medical Physiology
  • 1115 Pharmacology and Pharmaceutical Sciences