Abstract
Background: Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy. Methods: The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical analysis of plasma proteomics used independent sample t tests, correlations, linear regression, and robust regression models to determine network signaling and predictors of clinical outcomes. Data and network analyses were performed using IBM SPSS Statistics, SAS v 9.4, and STRING V11. Results: Increased systemic (p<0.001) and intracranial (p=0.013) levels of VCAM1 were associated with the presence of hypertension. Intracranial VCAM1 was positively correlated to both infarct volume (p=0.032; r=0.34) and edema volume (p=0.026; r=0.35). The %∆ in NIHSS from admittance to discharge was found to be significantly correlated to both systemic (p=0.013; r = −0.409) and intracranial (p=0.011; r = −0.421) VCAM1 levels indicating elevated levels of systemic and intracranial VCAM1 are associated with reduced improvement of stroke severity based on NIHSS from admittance to discharge. STRING-generated analyses identified biologic functional descriptions as well as function-associated proteins from the predictive models of infarct and edema volume. Conclusions: The current study provides novel data on systemic and intracranial VCAM1 in relation to stroke comorbidities, stroke severity, functional outcomes, and the role VCAM1 plays in complex protein-protein signaling pathways. These data will allow future studies to develop predictive biomarkers and proteomic targets for drug development to improve our ability to treat a devastating pathology.
Original language | English |
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Article number | 109 |
Journal | Journal of Neuroinflammation |
Volume | 18 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2021 |
Bibliographical note
Funding Information:The project described was supported by the National Center for Advancing Translational Sciences, through grant UL1TR001998 and UKHealthCare.
Publisher Copyright:
© 2021, The Author(s).
Keywords
- Biomarkers
- Infarct volume
- Ischemic stroke
- Mechanical thrombectomy
- Proteomics
- Vascular cell adhesion molecule 1
ASJC Scopus subject areas
- Neuroscience (all)
- Immunology
- Neurology
- Cellular and Molecular Neuroscience