Plasma and urine metabolomic analyses in aortic valve stenosis reveal shared and biofluid-specific changes in metabolite levels

PLoS One. 2020 Nov 25;15(11):e0242019. doi: 10.1371/journal.pone.0242019. eCollection 2020.

Abstract

Aortic valve stenosis (AVS) is a prevalent condition among the elderly population that eventually requires aortic valve replacement. The lack of reliable biomarkers for AVS poses a challenge for its early diagnosis and the application of preventive measures. Untargeted gas chromatography mass spectrometry (GC-MS) metabolomics was applied in 46 AVS cases and 46 controls to identify plasma and urine metabolites underlying AVS risk. Multivariate data analyses were performed on pre-processed data (e.g. spectral peak alignment), in order to detect changes in metabolite levels in AVS patients and to evaluate their performance in group separation and sensitivity of AVS prediction, followed by regression analyses to test for their association with AVS. Through untargeted analysis of 190 urine and 130 plasma features that could be detected and quantified in the GC-MS spectra, we identified contrasting levels of 22 urine and 21 plasma features between AVS patients and control subjects. Following metabolite assignment, we observed significant changes in the concentration of known metabolites in urine (n = 14) and plasma (n = 15) that distinguish the metabolomic profiles of AVS patients from healthy controls. Associations with AVS were replicated in both plasma and urine for about half of these metabolites. Among these, 2-Oxovaleric acid, elaidic acid, myristic acid, palmitic acid, estrone, myo-inositol showed contrasting trends of regulation in the two biofluids. Only trans-Aconitic acid and 2,4-Di-tert-butylphenol showed consistent patterns of regulation in both plasma and urine. These results illustrate the power of metabolomics in identifying potential disease-associated biomarkers and provide a foundation for further studies towards early diagnostic applications in severe heart conditions that may prevent surgery in the elderly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aortic Valve / metabolism*
  • Aortic Valve Stenosis / blood
  • Aortic Valve Stenosis / metabolism*
  • Aortic Valve Stenosis / urine
  • Biomarkers / blood*
  • Biomarkers / urine*
  • Case-Control Studies
  • Echocardiography / methods
  • Female
  • Gas Chromatography-Mass Spectrometry / methods
  • Heart Valve Prosthesis
  • Humans
  • Male
  • Metabolomics / methods
  • Middle Aged
  • Multivariate Analysis
  • Plasma / metabolism*
  • Regression Analysis
  • Urinalysis / methods
  • Urine / chemistry*

Substances

  • Biomarkers

Grants and funding

C Al Hageg is funded by a PhD studentship of the Lebanese National Center for Scientific Research. R Khnayzer acknowledges support from the School Research and Development Council at the Lebanese American University (srdc-r-2017-20). The patient cohort was collected by P Zalloua with the financial support from the European Commission (FGENTCARD, LSHGCT-2006-037683). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.