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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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.
KeywordsBiomarkers Ischemic stroke Clusterin Cystatin C Proteomics
We thank Dr. Jin-Moo Lee of Washington University in St. Louis for scientific comments and Mr. Garrett Ungerer for editing of the manuscript.
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.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Statement of Human Rights/Statement on the Welfare of Animals
Ethical approval for human rights: “All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.”
Ethical Approval for the Welfare of Animals
“All procedures performed in studies involving animals were in accordance with the ethical standards of the University of Missouri approved protocols for the Care and Use of Laboratory Animals at which the studies were conducted.”
“Informed consent was obtained from all individual participants included in the study.”
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