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Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease

Background: Cerebral small vessel disease (SVD) is associated with increased risk of stroke and dementia. Progressive damage to the cerebral microvasculature may also trigger angiogenic processes to promote vessel repair. Elevated levels of circulating endothelial progenitor cells (EPCs) and pro-ang...

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Autores principales: Kapoor, Arunima, Gaubert, Aimée, Marshall, Anisa, Meier, Irene B., Yew, Belinda, Ho, Jean K., Blanken, Anna E., Dutt, Shubir, Sible, Isabel J., Li, Yanrong, Jang, Jung Yun, Brickman, Adam M., Rodgers, Kathleen, Nation, Daniel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510558/
https://www.ncbi.nlm.nih.gov/pubmed/34650423
http://dx.doi.org/10.3389/fnagi.2021.711784
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author Kapoor, Arunima
Gaubert, Aimée
Marshall, Anisa
Meier, Irene B.
Yew, Belinda
Ho, Jean K.
Blanken, Anna E.
Dutt, Shubir
Sible, Isabel J.
Li, Yanrong
Jang, Jung Yun
Brickman, Adam M.
Rodgers, Kathleen
Nation, Daniel A.
author_facet Kapoor, Arunima
Gaubert, Aimée
Marshall, Anisa
Meier, Irene B.
Yew, Belinda
Ho, Jean K.
Blanken, Anna E.
Dutt, Shubir
Sible, Isabel J.
Li, Yanrong
Jang, Jung Yun
Brickman, Adam M.
Rodgers, Kathleen
Nation, Daniel A.
author_sort Kapoor, Arunima
collection PubMed
description Background: Cerebral small vessel disease (SVD) is associated with increased risk of stroke and dementia. Progressive damage to the cerebral microvasculature may also trigger angiogenic processes to promote vessel repair. Elevated levels of circulating endothelial progenitor cells (EPCs) and pro-angiogenic signaling proteins are observed in response to vascular injury. We aimed to examine circulating levels of EPCs and proangiogenic proteins in older adults with evidence of SVD. Methods: Older adults (ages 55–90) free of dementia or stroke underwent venipuncture and brain magnetic resonance imaging (MRI). Flow cytometry quantified circulating EPCs as the number of cells in the lymphocyte gate positively expressing EPC surface markers (CD34+CD133+CD309+). Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, and Flt-1). Total SVD burden score was determined based on MRI markers, including white matter hyperintensities, cerebral microbleeds and lacunes. Results: Sixty-four older adults were included. Linear regression revealed that older adults with higher circulating EPC levels exhibited greater total SVD burden [β = 1.0 × 10(5), 95% CI (0.2, 1.9), p = 0.019], after accounting for age and sex. Similarly, a positive relationship between circulating VEGF-D and total SVD score was observed, controlling for age and sex [β = 0.001, 95% CI (0.000, 0.001), p = 0.048]. Conclusion: These findings suggest that elevated levels of circulating EPCs and VEGF-D correspond with greater cerebral SVD burden in older adults. Additional studies are warranted to determine whether activation of systemic angiogenic growth factors and EPCs represents an early attempt to rescue the vascular endothelium and repair damage in SVD.
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spelling pubmed-85105582021-10-13 Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease Kapoor, Arunima Gaubert, Aimée Marshall, Anisa Meier, Irene B. Yew, Belinda Ho, Jean K. Blanken, Anna E. Dutt, Shubir Sible, Isabel J. Li, Yanrong Jang, Jung Yun Brickman, Adam M. Rodgers, Kathleen Nation, Daniel A. Front Aging Neurosci Aging Neuroscience Background: Cerebral small vessel disease (SVD) is associated with increased risk of stroke and dementia. Progressive damage to the cerebral microvasculature may also trigger angiogenic processes to promote vessel repair. Elevated levels of circulating endothelial progenitor cells (EPCs) and pro-angiogenic signaling proteins are observed in response to vascular injury. We aimed to examine circulating levels of EPCs and proangiogenic proteins in older adults with evidence of SVD. Methods: Older adults (ages 55–90) free of dementia or stroke underwent venipuncture and brain magnetic resonance imaging (MRI). Flow cytometry quantified circulating EPCs as the number of cells in the lymphocyte gate positively expressing EPC surface markers (CD34+CD133+CD309+). Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, and Flt-1). Total SVD burden score was determined based on MRI markers, including white matter hyperintensities, cerebral microbleeds and lacunes. Results: Sixty-four older adults were included. Linear regression revealed that older adults with higher circulating EPC levels exhibited greater total SVD burden [β = 1.0 × 10(5), 95% CI (0.2, 1.9), p = 0.019], after accounting for age and sex. Similarly, a positive relationship between circulating VEGF-D and total SVD score was observed, controlling for age and sex [β = 0.001, 95% CI (0.000, 0.001), p = 0.048]. Conclusion: These findings suggest that elevated levels of circulating EPCs and VEGF-D correspond with greater cerebral SVD burden in older adults. Additional studies are warranted to determine whether activation of systemic angiogenic growth factors and EPCs represents an early attempt to rescue the vascular endothelium and repair damage in SVD. Frontiers Media S.A. 2021-09-28 /pmc/articles/PMC8510558/ /pubmed/34650423 http://dx.doi.org/10.3389/fnagi.2021.711784 Text en Copyright © 2021 Kapoor, Gaubert, Marshall, Meier, Yew, Ho, Blanken, Dutt, Sible, Li, Jang, Brickman, Rodgers and Nation. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging Neuroscience
Kapoor, Arunima
Gaubert, Aimée
Marshall, Anisa
Meier, Irene B.
Yew, Belinda
Ho, Jean K.
Blanken, Anna E.
Dutt, Shubir
Sible, Isabel J.
Li, Yanrong
Jang, Jung Yun
Brickman, Adam M.
Rodgers, Kathleen
Nation, Daniel A.
Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease
title Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease
title_full Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease
title_fullStr Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease
title_full_unstemmed Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease
title_short Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease
title_sort increased levels of circulating angiogenic cells and signaling proteins in older adults with cerebral small vessel disease
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510558/
https://www.ncbi.nlm.nih.gov/pubmed/34650423
http://dx.doi.org/10.3389/fnagi.2021.711784
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