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Longitudinal stroke recovery associated with dysregulation of complement system - A proteomics pathway analysis

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Nguyen, VA, Riddell, N, Crewther, SG, Faou, P, Rajapaksha, H, Howells, DW ORCID: 0000-0002-2512-7724, Hankey, GJ, Wijeratne, T, Ma, H, Davis, S, Donnan, GA and Carey, LM 2020 , 'Longitudinal stroke recovery associated with dysregulation of complement system - A proteomics pathway analysis' , Frontiers in Neurology, vol. 11 , pp. 1-12 , doi: 10.3389/fneur.2020.00692.

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Abstract

Currently the longitudinal proteomic profile of post-ischemic stroke recovery is relativelyunknown with few well-accepted biomarkers or understanding of the biological systemsthat underpin recovery. We aimed to characterize plasma derived biological pathwaysassociated with recovery during the first year post event using a discovery proteomicsworkflow coupled with a topological pathway systems biology approach. Blood samples(n = 180, ethylenediaminetetraacetic acid plasma) were collected from a subgroup of60 first episode stroke survivors from the Australian START study at 3 timepoints: 3–7days (T1), 3-months (T2) and 12-months (T3) post-stroke. Samples were analyzed byliquid chromatography mass spectrometry using label-free quantification (data availableat ProteomeXchange with identifier PXD015006). Differential expression analysis revealedthat 29 proteins between T1 and T2, and 33 proteins between T1 and T3 weresignificantly different, with 18 proteins commonly differentially expressed across thetwo time periods. Pathway analysis was conducted using Gene Graph EnrichmentAnalysis on both the Kyoto Encyclopedia of Genes and Genomes and Reactomedatabases. Pathway analysis revealed that the significantly differentiated proteinsbetween T1 and T2 were consistently found to belong to the complement pathway.Further correlational analyses utilized to examine the changes in regulatory effects ofproteins over time identified significant inhibitory regulation of clusterin on complementcomponent 9. Longitudinal post-stroke blood proteomics profiles suggest that thealternative pathway of complement activation remains in a state of higher activation from3-7 days to 3 months post-stroke, while simultaneously being regulated by clusterin andvitronectin. These findings also suggest that post-stroke induced sterile inflammation andimmunosuppression could inhibit recovery within the 3-month window post-stroke.

Item Type: Article
Authors/Creators:Nguyen, VA and Riddell, N and Crewther, SG and Faou, P and Rajapaksha, H and Howells, DW and Hankey, GJ and Wijeratne, T and Ma, H and Davis, S and Donnan, GA and Carey, LM
Keywords: longitudinal, stroke, proteomics, immune system, complement system, bioinformatics, systems biology, pathway analysis
Journal or Publication Title: Frontiers in Neurology
Publisher: Frontiers Research Foundation
ISSN: 1664-2295
DOI / ID Number: 10.3389/fneur.2020.00692
Copyright Information:

Copyright 2020 Nguyen, Riddell, Crewther, Faou, Rajapaksha, Howells, Hankey,Wijeratne, Ma, Davis, Donnan and Carey. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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