Metabolomics

, Volume 3, Issue 4, pp 413–426 | Cite as

Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2-oxoglutarate

  • Warwick B. Dunn
  • David I. Broadhurst
  • Sasalu M. Deepak
  • Mamta H. Buch
  • Garry McDowell
  • Irena Spasic
  • David I. Ellis
  • Nicholas Brooks
  • Douglas B. Kell
  • Ludwig Neyses
Article

Abstract

There is intense interest in the identification of novel biomarkers which improve the diagnosis of heart failure. Serum samples from 52 patients with systolic heart failure (EF < 40% plus signs and symptoms of failure) and 57 controls were analyzed by gas chromatography – time of flight – mass spectrometry and the raw data reduced to 272 statistically robust metabolite peaks. 38 peaks showed a significant difference between case and control (p < 5 × 10−5). Two such metabolites were pseudouridine, a modified nucleotide present in t- and rRNA and a marker of cell turnover, as well as the tricarboxylic acid cycle intermediate 2-oxoglutarate. Furthermore, 3 further new compounds were also excellent discriminators between patients and controls: 2-hydroxy, 2-methylpropanoic acid, erythritol and 2,4,6-trihydroxypyrimidine. Although renal disease may be associated with heart failure, and metabolites associated with renal disease and other markers were also elevated (e.g. urea, creatinine and uric acid), there was no correlation within the patient group between these metabolites and our heart failure biomarkers, indicating that these were indeed biomarkers of heart failure and not renal disease per se. These findings demonstrate the power of data-driven metabolomics approaches to identify such markers of disease.

Keywords

heart failure metabolomics biomarkers pseudouridine 2-oxoglutarate 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Warwick B. Dunn
    • 1
    • 2
  • David I. Broadhurst
    • 2
  • Sasalu M. Deepak
    • 3
    • 4
  • Mamta H. Buch
    • 3
  • Garry McDowell
    • 5
  • Irena Spasic
    • 1
    • 2
  • David I. Ellis
    • 2
  • Nicholas Brooks
    • 4
  • Douglas B. Kell
    • 1
    • 2
  • Ludwig Neyses
    • 3
  1. 1.The Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary BiocentreThe University of ManchesterManchesterUK
  2. 2.School of Chemistry, Manchester Interdisciplinary BiocentreThe University of ManchesterManchesterUK
  3. 3.Division of Cardiovascular and Endocrine SciencesThe University of ManchesterManchesterUK
  4. 4.Department of CardiologySouth Manchester University HospitalManchesterUK
  5. 5.Department of Clinical BiochemistryManchester Royal InfirmaryManchesterUK

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