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From Analysis of Ischemic Mouse Brain Proteome to Identification of Human Serum Clusterin as a Potential Biomarker for Severity of Acute Ischemic Stroke

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Abstract

Ischemic stroke is a devastating neurological disease that can cause permanent brain damage, but to date, few biomarkers are available to reliably assess the severity of injury during acute onset. In this study, quantitative proteomic analysis of ischemic mouse brain detected the increase in expression levels of clusterin (CLU) and cystatin C (CST3). Since CLU is a secretary protein, serum samples (n = 70) were obtained from acute ischemic stroke (AIS) patients within 24 h of stroke onset and together with 70 matched health controls. Analysis of CLU levels indicated significantly higher levels in AIS patients than healthy controls (14.91 ± 4.03 vs. 12.79 ± 2.22 ng/L; P = 0.0004). Analysis of serum CST3 also showed significant increase in AIS patients as compared with healthy controls (0.90 ± 0.19 vs. 0.84 ± 0.12 ng/L; P = 0.0064). The serum values of CLU were also positively correlated with the NIH Stroke Scale (NIHSS) scores, the time interval after stroke onset, as well as major stroke risk factors associated with lipid profile. These data demonstrate that elevated levels of serum CLU and CST3 are independently associated with AIS and may serve as peripheral biomarkers to aid clinical assessment of AIS and its severity. This pilot study thus contributes to progress toward preclinical proteomic screening by using animal models and allows translation of results from bench to bedside.

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Acknowledgements

We thank Dr. Jin-Moo Lee of Washington University in St. Louis for scientific comments and Mr. Garrett Ungerer for editing of the manuscript.

Funding Sources

This work is partially supported by a research fund from the Department of Pathology and Anatomical Sciences at the University of Missouri-Columbia (MU) (ZG) and by a grant from the National Institutes of Health National Center for Complementary and Integrative Health (P50AT006273) to the MU Center for Botanical Interaction Studies. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Pathology & Anatomical Sciences, University of Missouri, Columbia, MO, 65211, USA

    Hailong Song, Hui Zhou, Zhe Qu, Dennis Y. Chuang, Shanyan Chen, Grace Y. Sun, Jiankun Cui & Zezong Gu

  2. Center for Botanical Interaction Studies, University of Missouri, Columbia, MO, 65211, USA

    Hailong Song, Hui Zhou, Zhe Qu, Jie Hou, Dennis Y. Chuang, Shanyan Chen, Jilong Li, Jianlin Cheng, Agnes Simonyi, Grace Y. Sun, Jiankun Cui & Zezong Gu

  3. Computer Science, University of Missouri, Columbia, MO, 65211, USA

    Jie Hou, Jilong Li & Jianlin Cheng

  4. Department of Neurology, the Second Affiliated Clinical College of Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, China

    Weilong Chen, Weiwu Cai & Chenghan Wu

  5. Department of Neurology, Fujian Provincial Hospital, Fuzhou, 350001, China

    Qiong Cheng

  6. Biochemistry, University of Missouri, Columbia, MO, 65211, USA

    Dennis Y. Chuang, Agnes Simonyi & Grace Y. Sun

  7. Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA

    Shuwei Li

  8. Chemistry, University of Missouri, Columbia, MO, 65211, USA

    C. Michael Greenlief

  9. Xiphophorus Genetic Stock Center, Texas State University, San Marcos, TX, 78666, USA

    Yuan Lu

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Song, H., Zhou, H., Qu, Z. et al. From Analysis of Ischemic Mouse Brain Proteome to Identification of Human Serum Clusterin as a Potential Biomarker for Severity of Acute Ischemic Stroke. Transl. Stroke Res. 10, 546–556 (2019). https://doi.org/10.1007/s12975-018-0675-2

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