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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.711784/full |
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| author | Arunima Kapoor Aimée Gaubert Anisa Marshall Irene B. Meier Irene B. Meier Belinda Yew Jean K. Ho Anna E. Blanken Shubir Dutt Isabel J. Sible Yanrong Li Jung Yun Jang Adam M. Brickman Kathleen Rodgers Daniel A. Nation Daniel A. Nation |
| author_facet | Arunima Kapoor Aimée Gaubert Anisa Marshall Irene B. Meier Irene B. Meier Belinda Yew Jean K. Ho Anna E. Blanken Shubir Dutt Isabel J. Sible Yanrong Li Jung Yun Jang Adam M. Brickman Kathleen Rodgers Daniel A. Nation Daniel A. Nation |
| author_sort | Arunima Kapoor |
| collection | DOAJ |
| 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 × 105, 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. |
| first_indexed | 2024-12-21T03:55:57Z |
| format | Article |
| id | doaj.art-7247d46be7734b8fbeabd689f2ae93f7 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-21T03:55:57Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-7247d46be7734b8fbeabd689f2ae93f72022-12-21T19:16:50ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-09-011310.3389/fnagi.2021.711784711784Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel DiseaseArunima Kapoor0Aimée Gaubert1Anisa Marshall2Irene B. Meier3Irene B. Meier4Belinda Yew5Jean K. Ho6Anna E. Blanken7Shubir Dutt8Isabel J. Sible9Yanrong Li10Jung Yun Jang11Adam M. Brickman12Kathleen Rodgers13Daniel A. Nation14Daniel A. Nation15Department of Psychological Science, University of California, Irvine, Irvine, CA, United StatesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United StatesDepartment of Psychology, University of Southern California, Los Angeles, CA, United StatesDepartment of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, United StatesChione GmbH, Binz, SwitzerlandDepartment of Psychology, University of Southern California, Los Angeles, CA, United StatesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United StatesDepartment of Psychology, University of Southern California, Los Angeles, CA, United StatesDepartment of Psychology, University of Southern California, Los Angeles, CA, United StatesDepartment of Psychology, University of Southern California, Los Angeles, CA, United StatesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United StatesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United StatesDepartment of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, United StatesCenter for Innovation in Brain Science, Department of Pharmacology, The University of Arizona, Tucson, AZ, United StatesDepartment of Psychological Science, University of California, Irvine, Irvine, CA, United StatesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United StatesBackground: 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 × 105, 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.https://www.frontiersin.org/articles/10.3389/fnagi.2021.711784/fullvascular endothelial growth factorendothelial progenitor cellscerebral microvascular pathologycerebral small vessel diseaseagingvascular dementia |
| spellingShingle | Arunima Kapoor Aimée Gaubert Anisa Marshall Irene B. Meier Irene B. Meier Belinda Yew Jean K. Ho Anna E. Blanken Shubir Dutt Isabel J. Sible Yanrong Li Jung Yun Jang Adam M. Brickman Kathleen Rodgers Daniel A. Nation Daniel A. Nation Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease Frontiers in Aging Neuroscience vascular endothelial growth factor endothelial progenitor cells cerebral microvascular pathology cerebral small vessel disease aging vascular dementia |
| 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 | vascular endothelial growth factor endothelial progenitor cells cerebral microvascular pathology cerebral small vessel disease aging vascular dementia |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.711784/full |
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