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.

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

Journal: Journal of proteome research 2021;20(10):4758-4770

PMID: 34473513

Free Full Text on American Chemical Society View on PubMed

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.

Address: Magnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, Sesto Fiorentino, Florence 50019, Italy.; Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.), Via Luigi Sacconi 6, Sesto Fiorentino, Florence 50019, Italy.; Department of Chemistry, University of Florence, Via della Lastruccia, 3, Sesto Fiorentino, Florence 50019, Italy.; Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, Florence 50134, Italy.; Atherothrombotic Diseases Center, Careggi Hospital, Florence, Largo Brambilla 3, Florence 50134, Italy.; Excellence Centre for Research, Transfer and High Education for the Development of DE NOVO Therapies (DENOTHE), University of Florence, Viale Pieraccini 6, Firenze 50139, Italy.; Stroke Unit, Careggi University Hospital, Florence 50134, Italy.; Institute of Neuroscience, Italian National Research Council (CNR), Via Madonna del Piano, 10, Sesto Fiorentino, Florence 50019, Italy.; NEUROFARBA Department, Neuroscience Section, University of Florence, Largo Brambilla 3, Florence 50134, Italy.; Department of Neurology, Careggi University Hospital, Largo Brambilla 3, Florence 50134, Italy.; Laboratory of Systems and Synthetic Biology, Wageningen University & Research, Stippeneng 4, Wageningen 6708 WE, the Netherlands.

DOI: 10.1021/acs.jproteome.1c00406

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https://medlineplus.gov/ischemicstroke.html

MeSH Terms: Humans, Ischemic Stroke, Lipids, Metabolomics, Thrombolytic Therapy, Tissue Plasminogen Activator, Treatment Outcome