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 F. Fraser; Keith R. Pennypacker

doi:10.1016/j.neuint.2022.105421

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 F. Fraser, Keith R. Pennypacker

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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 language	English
Article number	105421
Journal	Neurochemistry International
Volume	160
DOIs	https://doi.org/10.1016/j.neuint.2022.105421
State	Published - 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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10.1016/j.neuint.2022.105421

Cite this

Hazelwood, H. S., Frank, J. A., Maglinger, B., McLouth, C. J., Trout, A. L., Turchan-Cholewo, J., Stowe, A. M., Pahwa, S., Dornbos, D. L., Fraser, J. F., & Pennypacker, K. R. (2022). Plasma protein alterations during human large vessel stroke: A controlled comparison study. Neurochemistry International, 160, Article 105421. https://doi.org/10.1016/j.neuint.2022.105421

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title = "Plasma protein alterations during human large vessel stroke: A controlled comparison study",

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",

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

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: {\textcopyright} 2022 Elsevier Ltd",

year = "2022",

month = nov,

doi = "10.1016/j.neuint.2022.105421",

language = "English",

volume = "160",

}

TY - JOUR

T1 - Plasma protein alterations during human large vessel stroke

T2 - A controlled comparison study

AU - Hazelwood, Hunter S.

AU - Frank, Jacqueline A.

AU - Maglinger, Benton

AU - McLouth, Christopher J.

AU - Trout, Amanda L.

AU - Turchan-Cholewo, Jadwiga

AU - Stowe, Ann M.

AU - Pahwa, Shivani

AU - Dornbos, David L.

AU - Fraser, Justin F.

AU - Pennypacker, Keith R.

N1 - 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

PY - 2022/11

Y1 - 2022/11

N2 - 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.

AB - 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.

KW - Inflammation

KW - Mechanical thrombectomy

KW - Stroke

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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