Longitudinal Study Reveals Long-Term Proinflammatory Proteomic Signature After Ischemic Stroke Across Subtypes

Author:

Stanne Tara M.1ORCID,Angerfors Annelie1ORCID,Andersson Björn2ORCID,Brännmark Cecilia1ORCID,Holmegaard Lukas34ORCID,Jern Christina15ORCID

Affiliation:

1. Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Sweden (T.M.S., A.A., C.B., C.J.).

2. Bioinformatics Core Facility, University of Gothenburg, Sweden (B.A.).

3. Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, the Sahlgrenska Academy, University of Gothenburg, Sweden (L.H.).

4. Department of Neurology (L.H.), Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.

5. Department of Clinical Genetics and Genomics (C.J.), Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.

Abstract

Background: Inflammation contributes both to the pathogenesis of stroke and the response to brain injury. We aimed to identify proteins reflecting the acute-phase response and proteins more likely to reflect proinflammatory processes present before stroke by broadly profiling inflammation-related plasma proteins in a longitudinal ischemic stroke study. Methods: Participants were from a Swedish ischemic stroke cohort (SAHLSIS [Sahlgrenska Academy Study on Ischemic Stroke], n=600 cases and n=600 controls). Plasma levels of 65 proteins including chemokines, interleukins, surface molecules, and immune receptors were measured once in controls and at 3× in cases: during the acute phase, after 3 months, and for a subgroup (n=223) at 7-year follow-up. Associations between proteins and ischemic stroke or subtype were investigated in multivariable binary regression models corrected for age, sex, vascular risk factors, and multiple testing. Results: In the acute phase, 48 proteins were significantly and independently associated with ischemic stroke (false discovery rate adjusted P <0.05). At 3-month follow-up, 51 proteins and at 7-year follow-up 50 proteins were associated with ischemic stroke. The majority of proteins were upregulated in cases compared with controls (n=34 at all time points) and the most upregulated were CXCL5 (CXC chemokine ligand 5) and OSM (oncostatin M). Generally, large artery and cardioembolic stroke had the highest protein levels. However, several interesting subtype-specific differences were also detected at each time point. Conclusions: We found inflammation-related proteins that were differentially regulated in ischemic stroke cases compared with controls only in the acute phase and others that remained elevated also at later time points. This latter group of proteins could reflect underlying pathophysiological processes of relevance. Future studies both in terms of disease risk and prognostication are warranted.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Advanced and Specialized Nursing,Cardiology and Cardiovascular Medicine,Neurology (clinical)

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