Plasma protein alterations during human large vessel stroke: A controlled comparison study

Hunter S. Hazelwood, Jacqueline A. Frank, Benton Maglinger, Christopher J. McLouth, Amanda L. Trout, Jadwiga Turchan-Cholewo, Ann M. Stowe, Shivani Pahwa, David L. Dornbos, Justin Fraser, Keith R. Pennypacker

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Stroke is a major cause of death and disability in the United States. Mechanical thrombectomy (MT) and tissue plasminogen activator are the current treatments for ischemic stroke, which have improved clinical outcomes. Despite these treatments, functional and cognitive deficits still occur demonstrating a need for predictive biomarkers for beneficial clinical outcomes which can be used as therapeutic targets for pharmacotherapy. The aim of this study compares the proteomic expression of systemic arterial blood collected at the time of MT to those from a matched cerebrovascular disease (CVD) control cohort. Methods: The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683) collects and banks arterial blood, both distal and proximal to the thrombus, from ischemic stroke subjects undergoing MT. Arterial blood from patients undergoing a diagnostic angiogram was also collected and banked as CVD controls. Changes in cardiometabolic and inflammatory proteins between stroke and CVD controls were analyzed via Olink Proteomics. Results: Proteins including ARTN, TWEAK, HGF, CCL28, FGF-5, CXCL9, TRANCE and GDNF were found to be decreased in stroke subjects when compared to CVD controls. CXCL1, CCL5, OSM, GP1BA, IL6, MMP-1, and CXCL5 were increased in stroke subjects when compared to CVD controls. These proteins were also significantly correlated to stroke outcome metrics such as NIHSS, infarct volume and MoCA scoring. Conclusion: Overall, acute stroke patients had an increase in inflammatory proteins with a decrease in trophic proteins systemically compared to matched CVD controls. Using our CVD controls, proteins of interest were directly compared to stroke patients with the same cerebrovascular risk factors instead of statistically controlling for comorbidities. The novel methodology of matching an arterial blood CVD control group to a stroke group, as well as controlling for age and comorbid status add to the literature on prognostic stroke biomarkers, which are specific targets for future therapeutics.

Original languageEnglish
Article number105421
JournalNeurochemistry International
Volume160
DOIs
StatePublished - Nov 2022

Bibliographical note

Funding Information:
The Professional Student Mentored Research Fellowship (PSMRF) Project is supported by the National Center for Advancing Translational Sciences through Grant UL1TR001998, UK HealthCare and the University of Kentucky College of Medicine. The project was also supported by AHA EIA (19EIA34760279) to AMS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Funding Information:
The Professional Student Mentored Research Fellowship (PSMRF) Project is supported by the National Center for Advancing Translational Sciences through Grant UL1TR001998 , UK HealthCare and the University of Kentucky College of Medicine. The project was also supported by AHA EIA ( 19EIA34760279 ) to AMS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
© 2022 Elsevier Ltd

Keywords

  • Inflammation
  • Mechanical thrombectomy
  • Stroke

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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