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Acute Ischemic Stroke Severity, Progression, and Outcome Relate to Changes in Dipeptidyl Peptidase IV and Fibroblast Activation Protein Activity

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Abstract

Dipeptidyl peptidase IV (DPPIV) inhibition may be a promising therapeutic strategy for acute stroke treatment, given its potential to prolong the biological half-life of neuroprotective substrates. A related protease, fibroblast activation protein (FAP), was recently shown to inactivate the same substrates. Therefore, it should also be investigated as a potential target in stroke. The study aimed to investigate whether stroke severity and outcome correlate with DPPIV and FAP activities and their kinetics shortly after acute ischemic stroke. DPPIV and FAP activities were analyzed in the serum of 50 hyperacute stroke patients at admission, 1 day, 3 days, and 7 days after stroke onset and in 50 age-matched healthy controls. This was done as part of the Middelheim’s Interdisciplinary Stroke Study. DPPIV activity tended to increase shortly after stroke compared to the control population. DPPIV and FAP activities steadily decreased in the first week after stroke onset. Higher infarct volumes (≥5 ml) and a more severe stroke (NIHSS >7) at admission were correlated with a stronger decrease in the activities of both enzymes. Moreover, these patients more often developed a progressive stroke, were more often institutionalized. Patients with a stronger increase in DPPIV activity at admission and decrease in the activity of both DPPIV and FAP during the first week after stroke onset had a more severe stroke and worse short-term outcomes.

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Acknowledgments

We would like to thank Jill Luyckx (Institute Born-Bunge, Antwerp) for her logistic support with the serum samples and Nicole Lamoen (University of Antwerp) for her technical assistance. In addition, we are grateful to the Institute Born-Bunge and its Antwerp Biobank for providing the samples from the Middelheim Interdisciplinary Stroke Study project.

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Authors and Affiliations

  1. Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, Building S, room D.S.513, 2610, Wilrijk-Antwerp, Belgium

    Lesley Baerts, Kaat Kehoe, Robert Verkerk, Dirk Hendriks & Ingrid De Meester

  2. Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium

    Raf Brouns

  3. Center for Neurosciences, Vrije universiteit Brussel, Brussels, Belgium

    Raf Brouns

  4. Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium

    Sebastiaan Engelborghs & Peter Paul De Deyn

  5. Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge beuken, Antwerp, Belgium

    Sebastiaan Engelborghs & Peter Paul De Deyn

Authors
  1. Lesley Baerts
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  2. Raf Brouns
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  3. Kaat Kehoe
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  4. Robert Verkerk
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  5. Sebastiaan Engelborghs
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  6. Peter Paul De Deyn
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  7. Dirk Hendriks
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  8. Ingrid De Meester
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Corresponding author

Correspondence to Ingrid De Meester.

Ethics declarations

This work was supported by the University of Antwerp Research Fund (Grant FFB3551), the Institute Born-Bunge, the Antwerp Biobank, the Interuniversity Attraction Poles (IAP) program of the Belgian Science Policy Office, and the Flemish Government Methusalem excellence program, Belgium.

Conflict of Interest

The authors have no conflict of interest to declare. This study was conducted according to the Declaration of Helsinki and was approved by the Ethics Committees of ZNA Antwerp and the University of Antwerp. For the stroke patients of ZNA Middelheim hospital, written informed consent was obtained from each participating subject or proxy in case of reduced consciousness. The (leftover) control samples from the UZA hospital were number coded and were obtained according to the FDA “Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable.”

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Baerts, L., Brouns, R., Kehoe, K. et al. Acute Ischemic Stroke Severity, Progression, and Outcome Relate to Changes in Dipeptidyl Peptidase IV and Fibroblast Activation Protein Activity. Transl. Stroke Res. 8, 157–164 (2017). https://doi.org/10.1007/s12975-016-0493-3

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  • DOI: https://doi.org/10.1007/s12975-016-0493-3

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