eCite Digital Repository

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


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, Longitudinal stroke recovery associated with dysregulation of complement system - A proteomics pathway analysis, Frontiers in Neurology, 11 pp. 1-12. ISSN 1664-2295 (2020) [Refereed Article]


Copyright Statement

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)

DOI: doi:10.3389/fneur.2020.00692


Currently the longitudinal proteomic profile of post-ischemic stroke recovery is relatively unknown with few well-accepted biomarkers or understanding of the biological systems that underpin recovery. We aimed to characterize plasma derived biological pathways associated with recovery during the first year post event using a discovery proteomics workflow coupled with a topological pathway systems biology approach. Blood samples (n = 180, ethylenediaminetetraacetic acid plasma) were collected from a subgroup of 60 first episode stroke survivors from the Australian START study at 3 timepoints: 37 days (T1), 3-months (T2) and 12-months (T3) post-stroke. Samples were analyzed by liquid chromatography mass spectrometry using label-free quantification (data available at ProteomeXchange with identifier PXD015006). Differential expression analysis revealed that 29 proteins between T1 and T2, and 33 proteins between T1 and T3 were significantly different, with 18 proteins commonly differentially expressed across the two time periods. Pathway analysis was conducted using Gene Graph Enrichment Analysis on both the Kyoto Encyclopedia of Genes and Genomes and Reactome databases. Pathway analysis revealed that the significantly differentiated proteins between T1 and T2 were consistently found to belong to the complement pathway. Further correlational analyses utilized to examine the changes in regulatory effects of proteins over time identified significant inhibitory regulation of clusterin on complement component 9. Longitudinal post-stroke blood proteomics profiles suggest that the alternative pathway of complement activation remains in a state of higher activation from 3-7 days to 3 months post-stroke, while simultaneously being regulated by clusterin and vitronectin. These findings also suggest that post-stroke induced sterile inflammation and immunosuppression could inhibit recovery within the 3-month window post-stroke.

Item Details

Item Type:Refereed Article
Keywords:longitudinal, stroke, proteomics, immune system, complement system, bioinformatics, systems biology, pathway analysis
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Howells, DW (Professor David Howells)
ID Code:141040
Year Published:2020
Web of Science® Times Cited:3
Deposited By:Office of the School of Medicine
Deposited On:2020-09-21
Last Modified:2022-08-29
Downloads:17 View Download Statistics

Repository Staff Only: item control page