Abstract
Background: Metabolome profiling is used to identify biomarkers for acute ischemic stroke (AIS).
Previous studies compared metabolite profiles in AIS and healthy controls, which did
not account for factors that affect metabolome (genetics, medications). This pilot
project evaluates the change in metabolite concentrations between the acute and chronic
stage of stroke in the same cohort in order to minimize other factors impact. Methods: We performed global metabolome profile on serum of 20 and urine of 12 stroke patients
in acute (72 hours) and chronic (3-5.2 months) stage and compared relative peak values
using Wilcoxon and orthogonal partial least squares discriminant analysis methods.
Chronic stage metabolite concentrations were considered baseline. We performed analysis
to identify significantly overrepresented pathways using MetaboAnalyst. Results: Three serum metabolites asparagine (P = .045), tyrosine (P = .015), and xylose (P = .003) had significantly higher concentrations in acute stage. Seven out of top
10 serum metabolites ranked by Wilcoxon test P value were related to amino acid (AA) metabolism. Two urine metabolites glycine (P = .03) and acetylcarnitine (P = .05) had significantly different concentrations in the acute stage. Five of the
top 10 urine metabolites related to AA metabolism. We identified 6 significant pathways
after false discovery rate correction that were upregulated in the acute stage: (1)
Aminoacyl-tRNA synthesis, (2) nitrogen, (3) alanine, aspartate, and glutamate, (4)
branched-chain AA, (5) arginine and proline, and (6) phenylalanine metabolism. Conclusion: Longitudinal study design confirms that AA metabolism heavily involved in the pathophysiology
of acute brain ischemia. Prospective longitudinal studies with a higher number of
participants are needed to establish useful stroke biomarkers.
Key Words
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Article info
Publication history
Published online: January 20, 2020
Accepted:
December 19,
2019
Received in revised form:
December 5,
2019
Received:
September 17,
2019
Footnotes
Funding: This research was supported by the Presbyterian Health Foundation Team Science Grant and in part by USDA-NIFA NRI Integrated Grant 2009-55200-05197 funded to JV and Agriculture and Food Research Initiative competitive grant 2016-67017-24512 from the USDA National Institute of Food and Agriculture funded to LR. We thank the staff members of The University of Oklahoma Health Sciences Center and the Penn State Metabolomics Core Facility, University Park, PA, for assistance in this study.
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104618
Copyright
© 2019 Elsevier Inc. All rights reserved.
