Proteomic changes in intracranial blood during human ischemic stroke

Abstract

Background: Since 2015, mechanical thrombectomy has been the standard treatment for emergent large vessel occlusion ischemic stroke.

Objective: To investigate, using the previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683), how the protein expression of a patient's intracranial blood during ischemic stroke compares with the protein expression of their systemic arterial blood in order to better understand and treat stroke.

Methods: Plasma samples from 25 subjects underwent proteomic analysis, where intracranial protein expression was compared with systemic protein levels. Data including sex, comorbidities, infarct volume, and infarct time were included for each subject.

Results: A majority of important proteins had a lower expression in intracranial blood than in systemic arterial blood. Proteins with the most significant changes in expression were: endopeptidase at -0.26 (p<0.0001), phospholipid transfer protein (PLTP) at -0.26 (p=0.0005), uromodulin (UMOD) at -0.14 (p=0.002), ficolin-2 (FCN2) at -0.46 (p=0.005), C-C motif chemokine 19 (CCL19) at -0.51 (p<0.0001), C-C motif chemokine 20 (CCL20) at -0.40 (p<0.0001), fibroblast growth factor 21 at -0.37 (p=0.0002), and C-C motif chemokine (CCL23) at -0.43 (p=0.0003).

Conclusions: Evaluation of proteomic changes in the intravascular space of a cerebral infarct in progress in human subjects suggested that changes in proteins such PLTP, fetuin-B (FETUB), and FCN2 may be involved in atherosclerotic changes, and chemokines such as CCL23 are known to play a role in the Th2 autoimmune response. These data provide a scientific springboard for identifying clinically relevant biomarkers for diagnosis/prognosis, and targets for much needed neuroprotective/neuroreparative pharmacotherapies.

Keywords: artery; stroke; thrombectomy.

Conflict of interest statement

Competing interests: Authors KRP, AMS, and JFF are co-founders/equity holders in Cerelux, LLC.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Cardiometabolic panel volcano plot illustrating proteomic log2 fold changes in Normalized Protein eXpression (NPX) in intracranial blood compared with systemic blood. Labeled proteins include prolyl endopeptidase (FAP), phospholipid transfer protein (PLTP), fetuin-B (FETUB), uromodulin (UMOD), ficolin-2 (FCN2), and superoxide dismutase 1 (SOD1). Proteins with negative fold change are located to the left of the vertical line and indicate higher expression in systemic blood. Proteins located above the horizontal line are significant (p

Figure 2

Inflammatory panel volcano plot illustrating proteomic log2 fold changes in NormalizedProtein eXpression (NPX) in intracranial blood compared with systemic blood. Labeled proteins include C-C motif chemokine 19 (CCL19), C-C motif chemokine 20 (CCL20), fibroblast growth factor 21 (FGF21), transforming growth factor alfa (TGF-α), C-C motif chemokine 23 (CCL23), and axin-1 (AXIN1). Proteins with negative fold change are located to the left of the vertical line and indicate higher expression in systemic blood. Proteins located above the horizontal line are significant (p