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 3rd; Justin F Fraser; Keith R Pennypacker

doi:10.1016/j.neuint.2022.105421

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

Neurochem Int. 2022 Nov:160:105421. doi: 10.1016/j.neuint.2022.105421. Epub 2022 Sep 28.

Affiliations

¹ University of Kentucky College of Medicine, 800 Rose Street, MN 150, Lexington, KY, 40536, USA.
² University of Kentucky Department of Neurology, 740 S. Limestone Street, Kentucky Clinic J-455, Lexington, KY, 40536, USA; University of Kentucky Center for Advanced Translational Stroke Science, 741 S. Limestone Street, BBSRB B463, Lexington, KY, 40536, USA.
³ Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA.
⁴ University of Kentucky Department of Neurology, 740 S. Limestone Street, Kentucky Clinic J-455, Lexington, KY, 40536, USA; University of Kentucky Department of Biostatistics, 725 Rose Street, 205 Multidisciplinary Science Building, Lexington, KY, 40536, USA.
⁵ University of Kentucky Department of Neurosurgery, 780 Rose Street, Lexington, KY, 40536, USA; University of Kentucky Center for Advanced Translational Stroke Science, 741 S. Limestone Street, BBSRB B463, Lexington, KY, 40536, USA.
⁶ University of Kentucky Department of Neurology, 740 S. Limestone Street, Kentucky Clinic J-455, Lexington, KY, 40536, USA; University of Kentucky Department of Neuroscience, 741 S. Limestone Street, BBSRB 4th Floor, Lexington, KY, 40536, USA; University of Kentucky Center for Advanced Translational Stroke Science, 741 S. Limestone Street, BBSRB B463, Lexington, KY, 40536, USA.
⁷ University of Kentucky Department of Neurology, 740 S. Limestone Street, Kentucky Clinic J-455, Lexington, KY, 40536, USA; University of Kentucky Department of Neurosurgery, 780 Rose Street, Lexington, KY, 40536, USA; University of Kentucky Department of Radiology, 800 Rose Street, Lexington, KY, 40536, USA.
⁸ University of Kentucky Department of Neurosurgery, 780 Rose Street, Lexington, KY, 40536, USA; University of Kentucky Department of Radiology, 800 Rose Street, Lexington, KY, 40536, USA.
⁹ University of Kentucky Department of Neurology, 740 S. Limestone Street, Kentucky Clinic J-455, Lexington, KY, 40536, USA; University of Kentucky Department of Neurosurgery, 780 Rose Street, Lexington, KY, 40536, USA; University of Kentucky Department of Radiology, 800 Rose Street, Lexington, KY, 40536, USA; University of Kentucky Department of Neuroscience, 741 S. Limestone Street, BBSRB 4th Floor, Lexington, KY, 40536, USA; University of Kentucky Center for Advanced Translational Stroke Science, 741 S. Limestone Street, BBSRB B463, Lexington, KY, 40536, USA.
¹⁰ University of Kentucky Department of Neurology, 740 S. Limestone Street, Kentucky Clinic J-455, Lexington, KY, 40536, USA; University of Kentucky Department of Neuroscience, 741 S. Limestone Street, BBSRB 4th Floor, Lexington, KY, 40536, USA; University of Kentucky Center for Advanced Translational Stroke Science, 741 S. Limestone Street, BBSRB B463, Lexington, KY, 40536, USA. Electronic address: [email protected].

PMID: 36179808
DOI: 10.1016/j.neuint.2022.105421

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.

Keywords: Inflammation; Mechanical thrombectomy; Stroke.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Brain Ischemia* / drug therapy
Glial Cell Line-Derived Neurotrophic Factor
Humans
Interleukin-6
Ischemic Stroke*
Matrix Metalloproteinase 1
Proteomics
Stroke* / therapy
Tissue Plasminogen Activator
Treatment Outcome
United States

Substances

Glial Cell Line-Derived Neurotrophic Factor
Interleukin-6
Tissue Plasminogen Activator
Matrix Metalloproteinase 1

Associated data

ClinicalTrials.gov/NCT03153683

Grants and funding

UL1 TR001998/TR/NCATS NIH HHS/United States