TY - JOUR
T1 - Potential Metabolite Biomarkers for Acute Versus Chronic Stage of Ischemic Stroke
T2 - A Pilot Study
AU - Sidorov, Evgeny
AU - Bejar, Cynthia
AU - Xu, Chao
AU - Ray, Bappaditya
AU - Reddivari, Lavanya
AU - Chainakul, Juliane
AU - Vanamala, Jairam K.P.
AU - Sanghera, Dharambir K.
N1 - Funding Information:
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.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
KW - Metabolome
KW - amino acids
KW - biomarkers
KW - cerebral ischemia
KW - stroke
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U2 - 10.1016/j.jstrokecerebrovasdis.2019.104618
DO - 10.1016/j.jstrokecerebrovasdis.2019.104618
M3 - Article
C2 - 31973907
AN - SCOPUS:85078050465
SN - 1052-3057
VL - 29
JO - Journal of Stroke and Cerebrovascular Diseases
JF - Journal of Stroke and Cerebrovascular Diseases
IS - 4
M1 - 104618
ER -