Metabolome of cerebrovascular disease. Research methods and prospects for clinical application

Authors

DOI:

https://doi.org/10.32782/2415-8127.2024.69.26

Keywords:

metabolome, non-infectious diseases, cerebrovascular disease, diagnosis, prognosis

Abstract

The review is devoted to the prospects of applying metabolomic approaches to the diagnosis and prediction of the course of cerebrovascular disease. The main methods of research are defined, it is shown that metabolome studies can be useful for the development of new methods of clinical forecasting in patients with cerebrovascular disease. Evaluation of the metabolome allows to determine the phenotypes of the organism. Metabolites can be identified and classified using a number of different technologies, including nuclear magnetic resonance spectroscopy and mass spectrometry. At the same time, they must be combined with various forms of liquid chromatography, gas chromatography or capillary electrophoresis to facilitate the separation of compounds. Each method is typically capable of simultaneously identifying or characterizing 50-5,000 different metabolites or «features» of metabolites, depending on the instrument or protocol used. Today, it is impossible to analyze the entire spectrum of metabolites with one analytical method, so their combinations are used. There is evidence that multiple serum metabolites are associated with the severity of small vessel disease, including Fazekas class, cognitive decline, and dementia. According to the authors, further research is needed to determine whether these associations are robust causal relationships and whether they can be used to predict the rate of progression and severity of onset of lacunar stroke and dementia, both in clinical practice and in basic science. The authors conclude that the main methods of studying the metabolome are nuclear magnetic resonance spectroscopy and mass spectrometry, which will allow the development of new methods of predicting cerebrovascular diseases, and numerous serum metabolites are associated with the severity of small vessel disease.

References

Johnson CH, Ivanisevic J, Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol. 2016 Jul;17(7):451-9. doi: 10.1038/nrm.2016.25

Bujak R, Struck-Lewicka W, Markuszewski MJ, Kaliszan R. Metabolomics for laboratory diagnostics. J Pharm Biomed Anal. 2015 Sep 10;113:108-20. doi: 10.1016/j.jpba.2014.12.017.

Wang R, Li B, Lam SM, Shui G. Integration of lipidomics and metabolomics for in-depth understanding of cellular mechanism and disease progression. J Genet Genomics. 2020 Feb 20;47(2):69-83. doi: 10.1016/j.jgg.2019.11.009.

Chacko S, Haseeb YB, Haseeb S. Metabolomics Work Flow and Analytics in Systems Biology. Curr Mol Med. 2022;22(10):870-881. doi: 10.2174/1566524022666211217102105.

Metabolic Profiling: Its Role in Biomarker Discovery and Gene Function Analysis ed. Hariigan G., Goodacre R. Boston-Dordrecht-London Kluwer Academic Punlishers. 2003, 318.

Metabolomics. https://www.scimagojr.com/journalsearch.php?q=130171&tip=sid

Rinschen MM, Ivanisevic J, Giera M, Siuzdak G. Identification of bioactive metabolites using activity metabolomics. Nat Rev Mol Cell Biol. 2019 Jun;20(6):353-367. doi: 10.1038/s41580-019-0108-4.

Jang C, Chen L, Rabinowitz JD. Metabolomics and Isotope Tracing. Cell. 2018 May 3;173(4):822-837. doi: 10.1016/j.cell.2018.03.055.

Bauermeister A, Mannochio-Russo H, Costa-Lotufo LV, Jarmusch AK, Dorrestein PC. Mass spectrometry-based metabolomics in microbiome investigations. Nat Rev Microbiol. 2022 Mar;20(3):143-160. doi: 10.1038/s41579-021-00621-9.

Wang S, Blair IA, Mesaros C. Analytical Methods for Mass Spectrometry-Based Metabolomics Studies. Adv Exp Med : 31347076.

Human Metabolome Database https://hmdb.ca

Yeast Metabolome Database http://www.ymdb.ca

E.coli Metabolome Database https://ecmdb.ca

Mueller LA, Zhang P, Rhee SY (June 2003). “AraCyc: a biochemical pathway database for Arabidopsis”. Plant Physiology. 132 (2): 453–60. doi:10.1104/pp.102.017236.

Bouatra S, Aziat F, Mandal R, Guo AC, Wilson MR, Knox C, et al. (Sep 2013). “The human urine metabolome”. PLOS ONE. 8 (9): e73076.Bibcode:2013PLoSO...873076B. doi:10.1371/journal.pone.0073076.

Mandal R, Guo AC, Chaudhary KK, Liu P, Yallou FS, Dong E, et al. (April 2012). “Multi-platform characterization of the human cerebrospinal fluid metabolome: a comprehensive and quantitative update”. Genome Medicine. 4 (4): 38. doi:10.1186/gm337.

Psychogios N, Hau DD, Peng J, Guo AC, Mandal R, Bouatra S, et al. (February 2011). “The human serum metabolome”. PLOS ONE. 6 (2): e16957. Bibcode:2011PLoSO...616957P. doi:10.1371/journal.pone.0016957.

Kanehisa M, Goto S (January 2000). “KEGG: kyoto encyclopedia of genes and genomes”. Nucleic Acids Research. 28 (1): 27–30. doi:10.1093/nar/28.1.27.

Haug K, Salek RM, Conesa P, Hastings J, de Matos P, Rijnbeek M, et al. (January 2013). “MetaboLights--an open-access general-purpose repository for metabolomics studies and associated meta-data”. Nucleic Acids Research. 41 (Database issue): D781-6. doi:10.1093/nar/gks1004.

Kopka J, Schauer N, Krueger S, Birkemeyer C, Usadel B, Bergmüller E, et al. (April 2005). “GMD@CSB.DB: the Golm Metabolome Database”. Bioinformatics. 21 (8): 1635–8. doi:10.1093/bioinformatics/bti236.

Caspi R, Altman T, Dale JM, Dreher K, Fulcher CA, Gilham F, et al. (January 2010). “The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases”. Nucleic Acids Research. 38 (Database issue): D473-9. doi:10.1093/nar/gkp875.

Fahy E, Sud M, Cotter D, Subramaniam S (July 2007). “LIPID MAPS online tools for lipid research”. Nucleic Acids Research. 35 (Web Server issue): W606-12. doi:10.1093/nar/gkm324.

Smith CA, O’Maille G, Want EJ, Qin C, Trauger SA, Brandon TR, et al. (December 2005). “METLIN: a metabolite mass spectral database”. Therapeutic Drug Monitoring. 27 (6): 747–51. doi:10.1097/01.ftd.0000179845.53213.39.

Goldstein LB. Introduction for Focused Updates in Cerebrovascular Disease. Stroke. 2020 Mar;51(3):708-710. doi: 10.1161/STROKEAHA.119.024159.

Vargas-González JC, Hachinski V. Insidious Cerebrovascular Disease-The Uncool Iceberg. JAMA Neurol. 2020 Feb 1;77(2):155-156. doi: 10.1001/jamaneurol.2019.3933.

Shin TH, Lee DY, Basith S, Manavalan B, Paik MJ, Rybinnik I, Mouradian MM, Ahn JH, Lee G. Metabolome Changes in Cerebral Ischemia. Cells. 2020 Jul 7;9(7):1630. doi: 10.3390/cells9071630.

Qureshi MI, Vorkas PA, Coupland AP, Jenkins IH, Holmes E, Davies AH. Lessons from Metabonomics on the Neurobiology of Stroke. Neuroscientist. 2017 Aug;23(4):374-382. doi: 10.1177/1073858416673327.

Kim M, Jung S, Kim SY, Lee SH, Lee JH. Prehypertension-associated elevation in circulating lysophosphatidlycholines, Lp-PLA2 activity, and oxidative stress. PLoS One. 2014 May 6;9(5):e96735. doi: 10.1371/journal.pone.0096735.

Ke C, Shi M, Guo D, Zhu Z, Zhong C, Xu T, Lu Y, Ding Y, Zhang Y. Metabolomics on vascular events and death after acute ischemic stroke: A prospective matched nested case-control study. Atherosclerosis. 2022 Jun;351:1-8. doi: 10.1016/j.atherosclerosis.2022.05.001.

Suissa L, Guigonis JM, Graslin F, Robinet-Borgomano E, Chau Y, Sedat J, Lindenthal S, Pourcher T. Combined Omic Analyzes of Cerebral Thrombi: A New Molecular Approach to Identify Cardioembolic Stroke Origin. Stroke. 2021 Aug;52(9):2892-2901. doi: 10.1161/STROKEAHA.120.032129.

Poupore N, Chosed R, Arce S, Rainer R, Goodwin RL, Nathaniel TI. Metabolomic Profiles of Men and Women Ischemic Stroke Patients. Diagnostics (Basel). 2021 Sep 28;11(10):1786. doi: 10.3390/diagnostics11101786.

Harshfield EL, Sands CJ, Tuladhar AM, de Leeuw FE, Lewis MR, Markus HS. Metabolomic profiling in small vessel disease identifies multiple associations with disease severity. Brain. 2022 Jul 29;145(7):2461-2471. doi: 10.1093/brain/awac041.

Ma W, Yang YB, Xie TT, Xu Y, Liu N, Mo XN. Cerebral Small Vessel Disease: A Bibliometric Analysis. J Mol Neurosci. 2022 Nov;72(11):2345-2359. doi: 10.1007/s12031-022-02070-2.

Published

2024-05-16

How to Cite

Храмцов, Д. М., Стоянов, О. М., Пшеченко, К. М., Вікаренко, М. С., & Калашніков, В. Й. (2024). Metabolome of cerebrovascular disease. Research methods and prospects for clinical application. Scientific Bulletin of the Uzhhorod University. Series «Medicine», (1(69), 150-155. https://doi.org/10.32782/2415-8127.2024.69.26

Issue

Section

INTERDISCIPLINARY MEDICINE AND RELATED BRANCHES

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