Differential Network Analysis Reveals Metabolic Determinants Associated with Mortality in Acute Myocardial Infarction Patients and Suggests Potential Mechanisms Underlying Different Clinical Scores Used To Predict Death

Alessia Vignoli, Leonardo Tenori, Betti Giusti, Serafina Valente, Nazario Carrabba, Daniela Balzi, Alessandro Barchielli, Niccolò Marchionni, Gian Franco Gensini, Rossella Marcucci, Anna Maria Gori, Claudio Luchinat, Edoardo Saccenti

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We present here the differential analysis of metabolite-metabolite association networks constructed from an array of 24 serum metabolites identified and quantified via nuclear magnetic resonance spectroscopy in a cohort of 825 patients of which 123 died within 2 years from acute myocardial infarction (AMI). We investigated differences in metabolite connectivity of patients who survived, at 2 years, the AMI event, and we characterized metabolite-metabolite association networks specific to high and low risks of death according to four different risk parameters, namely, acute coronary syndrome classification, Killip, Global Registry of Acute Coronary Events risk score, and metabolomics NOESY RF risk score. We show significant differences in the connectivity patterns of several low-molecular-weight molecules, implying variations in the regulation of several metabolic pathways regarding branched-chain amino acids, alanine, creatinine, mannose, ketone bodies, and energetic metabolism. Our results demonstrate that the characterization of metabolite-metabolite association networks is a promising and powerful tool to investigate AMI patients according to their outcomes at a molecular level.

Original languageEnglish
Pages (from-to)949-961
Number of pages13
JournalJournal of Proteome Research
Volume19
Issue number2
DOIs
Publication statusPublished - 7 Feb 2020

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Keywords

  • acute myocardial infarction
  • metabolite−metabolite association networks
  • metabolomics
  • network inference
  • nuclear magnetic resonance

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