Analysis of Metabolite and Lipid Association Networks Reveals Molecular Mechanisms Associated with 3-Month Mortality and Poor Functional Outcomes in Patients with Acute Ischemic Stroke after Thrombolytic Treatment with Recombinant Tissue Plasminogen Activator

Cristina Licari, Leonardo Tenori, Betti Giusti, Elena Sticchi, Ada Kura, Rosina De Cario, Domenico Inzitari, Benedetta Piccardi, Mascia Nesi, Cristina Sarti, Francesco Arba, Vanessa Palumbo, Patrizia Nencini, Rossella Marcucci, Anna Maria Gori, Claudio Luchinat*, Edoardo Saccenti

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Here, we present an integrated multivariate, univariate, network reconstruction and differential analysis of metabolite-metabolite and metabolite-lipid association networks built from an array of 18 serum metabolites and 110 lipids identified and quantified through nuclear magnetic resonance spectroscopy in a cohort of 248 patients, of which 22 died and 82 developed a poor functional outcome within 3 months from acute ischemic stroke (AIS) treated with intravenous recombinant tissue plasminogen activator. We explored differences in metabolite and lipid connectivity of patients who did not develop a poor outcome and who survived the ischemic stroke from the related opposite conditions. We report statistically significant differences in the connectivity patterns of both low- and high-molecular-weight metabolites, implying underlying variations in the metabolic pathway involving leucine, glycine, glutamine, tyrosine, phenylalanine, citric, lactic, and acetic acids, ketone bodies, and different lipids, thus characterizing patients' outcomes. Our results evidence the promising and powerful role of the metabolite-metabolite and metabolite-lipid association networks in investigating molecular mechanisms underlying AIS patient's outcome.

Original languageEnglish
JournalJournal of Proteome Research
DOIs
Publication statusPublished - 2 Sep 2021

Keywords

  • lipidome
  • metabolomics
  • multivariate exploratory analysis
  • nuclear magnetic resonance
  • thrombolysis

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