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Metabolomic Characterization of Acute Ischemic Stroke Facilitates Metabolomic Biomarker Discovery

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Abstract

Acute ischemic stroke (AIS) is characterized by a sudden blockage of one of the main arteries supplying blood to the brain, leading to insufficient oxygen and nutrients for brain cells to function properly. Unfortunately, metabolic alterations in the biofluids with AIS are still not well understood. In this study, we performed high-throughput target metabolic analysis on 44 serum samples, including 22 from AIS patients and 22 from healthy controls. Multiple-reaction monitoring analysis of 180 common metabolites revealed a total of 29 metabolites that changed significantly (VIP > 1, p < 0.05). Multivariate statistical analysis unraveled a striking separation between AIS patients and healthy controls. Comparing the AIS group with the control group, the contents of argininosuccinic acid, beta-D-glucosamine, glycerophosphocholine, L-abrine, and L-pipecolic acid were remarkably downregulated in AIS patients. Twenty-nine out of 112 detected metabolites enriched in disturbed metabolic pathways, including aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, lysine degradation, phenylalanine, tyrosine, and tryptophan biosynthesis metabolic pathways. Collectively, these results will provide a sensitive, feasible diagnostic prospect for AIS patients.

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Data Availability

All data generated or analyzed during this study are available from the corresponding authors on reasonable request.

Abbreviations

AIS:

Acute ischemic stroke

CT:

Computed tomography

CTA:

Computed tomography angiography

MRI:

Magnetic resonance imaging

MRA:

Magnetic resonance angiography

MRM:

Multiple reaction monitoring

UPLC:

Ultra performance liquid chromatography

MS:

Mass spectrometry

NIHSS:

National Institutes of Health Stroke Scale

QC:

Quality control

PCA:

Principal component analysis

OPLS-DA:

Orthogonal projections to latent structures-discriminant analysis

VIP:

Variable importance in projection

ROC:

Receiver operating characteristic

AUC:

Area under curve

PtdCho:

Phosphatidylcholine

GroPCho:

Glycerophosphocholine

L-PA:

L-pipecolic acid

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Funding

This work was supported by Fujian Health Talent Training Project (2019–2-62), Xiamen Science and Technology Huimin Project (3502Z20184006), and Xiamen Medical and Health Technology Project (3502Z20194033, 3502Z20194028).

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Author notes

  1. Biao Qi, Yanyu Zhang, and Bing Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, 361015, China

    Biao Qi & Qiuping Li

  2. Institute of Analytical Technology and Smart Instruments, Xiamen Huaxia University, Xiamen, 361024, China

    Yanyu Zhang

  3. Department of Emergency Medicine, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, China

    Bing Xu

  4. Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Yuhao Zhang & Guoqiang Fei

  5. Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, 2999th Jinshan Road, Xiamen, 361000, China

    Ling Lin

  6. Department of Neurosurgery, Zhongshan Hospital, Fudan University, 180th Fenglin Road, Shanghai, 200032, China

    Qiuping Li

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  1. Biao Qi
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  4. Yuhao Zhang
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Contributions

All authors contributed to the study’s conception and design. The methodology was performed by Biao Qi and Yanyu Zhang. Data analysis and investigation were performed by Bing Xu and Guoqiang Fei. The original manuscript was written by Biao Qi, Yanyu Zhang, and Bing Xu, while the manuscript review and editing was done by Ling Lin and Qiuping Li. Funding acquisition was gained by Biao Qi, Guoqiang Fei, and Qiuping Li. Resources were prepared by Yuhao Zhang. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Ling Lin or Qiuping Li.

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This article contains a metabolomic study with human subjects. Ethical approval from the Research Ethics Committee from Xiamen Branch, Zhongshan Hospital of Fudan University was obtained.

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Qi, B., Zhang, Y., Xu, B. et al. Metabolomic Characterization of Acute Ischemic Stroke Facilitates Metabolomic Biomarker Discovery. Appl Biochem Biotechnol 194, 5443–5455 (2022). https://doi.org/10.1007/s12010-022-04024-1

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