Metabolomics in infectious diseases and drug discovery

Journal article

Carotid artery stenosis is mainly produced due to the progressive accumulation of atherosclerotic plaque in the vascular wall. The atherosclerotic plaque is characterized by the accumulation of lipids, low density proteins, expression of chemokines and adhesion molecules, and migration of monocytes and lymphocytes into the plaque. Its rupture can produce stroke, but embolic propensity depends principally on the composition and vulnerability of plaque rather than the severity of stenosis. It is important, then, to ascertain which patients with carotid artery stenosis have a greater risk of developing neurological symptomatology. Here, we present a metabolomic study by using nuclear magnetic resonance (NMR) spectroscopy in atheroma plaque and serum samples from patients with recently symptomatic and asymptomatic carotid stenosis to search for metabolites that could be used as biomarkers associated with plaque vulnerability and subsequent risk of rupture. Thirty-eight atheromatous plaque samples (24 asymptomatic patients and 14 symptomatic) and 70 serum samples (43 asymptomatic and 27 symptomatic) were studied by NMR spectroscopy. The data were analysed using multivariate statistics (PLS-DA) to determine a model to discriminate between symptomatic and asymptomatic samples (atheroma plaques and sera). The calculated PLS-DA models showed a 100 % sensitivity and a 96.6 % specificity for the cross validation to discriminate between symptomatic and asymptomatic plaques, and 88.37 % sensitivity and 77.78 % specificity when serum samples were analysed. According to the results of our multivariate and univariate analysis, the most discriminative metabolites for plaque vulnerability were threonine in serum samples, and glutamate in plaque samples. Also, an analysis of the main metabolic pathways involved in plaque vulnerability revealed that d-glutamine and d-glutamate metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis were the most affected pathways in plaque and serum, respectively

Authors: Tounta, V; Liu, Y; Cheyne, A; Larrouy-Maumus, G

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Royal Society of Chemistry
• Journal: Molecular Omics
• Volume: 17
• Issue: 3
• Pages: 376-393
• Publication date: 2021-04-12
• DOI: 10.1039/d1mo00017a
• EISSN: 2515-4184
• ISSN: 2515-4184
• Language: English
• Keywords: Genetics; Genome; Biomarker discovery; Druggability; Computational biology; Biology; Omics; Metabolomics; Drug discovery; Proteomics; Bioinformatics; Genomics