Pro-inflammatory Monocyte Phenotype During Acute Progression of Cerebral Small Vessel Disease
Background: The etiology of cerebral small vessel disease (SVD) remains elusive, though evidence is accumulating that inflammation contributes to its pathophysiology. We recently showed retrospectively that pro-inflammatory monocytes are associated with the long-term progression of white matter hype...
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Frontiers Media S.A.
2021-05-01
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Series: | Frontiers in Cardiovascular Medicine |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.639361/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marlies P. Noz Annemieke ter Telgte Kim Wiegertjes Anil M. Tuladhar Charlotte Kaffa Simone Kersten Simone Kersten Siroon Bekkering Charlotte D. C. C. van der Heijden Alexander Hoischen Alexander Hoischen Leo A. B. Joosten Leo A. B. Joosten Mihai G. Netea Mihai G. Netea Marco Duering Marco Duering Marco Duering Frank-Erik de Leeuw Niels P. Riksen |
spellingShingle |
Marlies P. Noz Annemieke ter Telgte Kim Wiegertjes Anil M. Tuladhar Charlotte Kaffa Simone Kersten Simone Kersten Siroon Bekkering Charlotte D. C. C. van der Heijden Alexander Hoischen Alexander Hoischen Leo A. B. Joosten Leo A. B. Joosten Mihai G. Netea Mihai G. Netea Marco Duering Marco Duering Marco Duering Frank-Erik de Leeuw Niels P. Riksen Pro-inflammatory Monocyte Phenotype During Acute Progression of Cerebral Small Vessel Disease Frontiers in Cardiovascular Medicine cerebral small vessel disease magnetic resonance imaging innate immunity monocyte inflammation |
author_facet |
Marlies P. Noz Annemieke ter Telgte Kim Wiegertjes Anil M. Tuladhar Charlotte Kaffa Simone Kersten Simone Kersten Siroon Bekkering Charlotte D. C. C. van der Heijden Alexander Hoischen Alexander Hoischen Leo A. B. Joosten Leo A. B. Joosten Mihai G. Netea Mihai G. Netea Marco Duering Marco Duering Marco Duering Frank-Erik de Leeuw Niels P. Riksen |
author_sort |
Marlies P. Noz |
title |
Pro-inflammatory Monocyte Phenotype During Acute Progression of Cerebral Small Vessel Disease |
title_short |
Pro-inflammatory Monocyte Phenotype During Acute Progression of Cerebral Small Vessel Disease |
title_full |
Pro-inflammatory Monocyte Phenotype During Acute Progression of Cerebral Small Vessel Disease |
title_fullStr |
Pro-inflammatory Monocyte Phenotype During Acute Progression of Cerebral Small Vessel Disease |
title_full_unstemmed |
Pro-inflammatory Monocyte Phenotype During Acute Progression of Cerebral Small Vessel Disease |
title_sort |
pro-inflammatory monocyte phenotype during acute progression of cerebral small vessel disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cardiovascular Medicine |
issn |
2297-055X |
publishDate |
2021-05-01 |
description |
Background: The etiology of cerebral small vessel disease (SVD) remains elusive, though evidence is accumulating that inflammation contributes to its pathophysiology. We recently showed retrospectively that pro-inflammatory monocytes are associated with the long-term progression of white matter hyperintensities (WMHs). In this prospective high-frequency imaging study, we hypothesize that the incidence of SVD progression coincides with a pro-inflammatory monocyte phenotype.Methods: Individuals with SVD underwent monthly magnetic resonance imaging (MRI) for 10 consecutive months to detect SVD progression, defined as acute diffusion-weighted imaging-positive (DWI+) lesions, incident microbleeds, incident lacunes, and WMH progression. Circulating inflammatory markers were measured, cytokine production capacity of monocytes was assessed after ex vivo stimulation, and RNA sequencing was performed on isolated monocytes in a subset of participants.Results: 13 out of 35 individuals developed SVD progression (70 ± 6 years, 54% men) based on incident lesions (n = 7) and/or upper quartile WMH progression (n = 9). Circulating E-selectin concentration (p < 0.05) and the cytokine production capacity of interleukin (IL)-1β and IL-6 (p < 0.01) were higher in individuals with SVD progression. Moreover, RNA sequencing revealed a pro-inflammatory monocyte signature including genes involved in myelination, blood–brain barrier, and endothelial–leukocyte interaction.Conclusions: Circulating monocytes of individuals with progressive SVD have an inflammatory phenotype, characterized by an increased cytokine production capacity and a pro-inflammatory transcriptional signature. |
topic |
cerebral small vessel disease magnetic resonance imaging innate immunity monocyte inflammation |
url |
https://www.frontiersin.org/articles/10.3389/fcvm.2021.639361/full |
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doaj-cb681f1b1f4042ff8dd4e7a06c198ac42021-05-13T04:29:05ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-05-01810.3389/fcvm.2021.639361639361Pro-inflammatory Monocyte Phenotype During Acute Progression of Cerebral Small Vessel DiseaseMarlies P. Noz0Annemieke ter Telgte1Kim Wiegertjes2Anil M. Tuladhar3Charlotte Kaffa4Simone Kersten5Simone Kersten6Siroon Bekkering7Charlotte D. C. C. van der Heijden8Alexander Hoischen9Alexander Hoischen10Leo A. B. Joosten11Leo A. B. Joosten12Mihai G. Netea13Mihai G. Netea14Marco Duering15Marco Duering16Marco Duering17Frank-Erik de Leeuw18Niels P. Riksen19Department of Internal Medicine, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, NetherlandsCenter for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Internal Medicine, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Internal Medicine, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Internal Medicine, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Internal Medicine, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Internal Medicine, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaDepartment of Internal Medicine, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, NetherlandsDepartment for Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, GermanyDepartment of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, NetherlandsInstitute for Stroke and Dementia Research, University Hospital of Munich, Munich, GermanyMunich Cluster for Systems Neurology, Munich, GermanyDepartment of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Internal Medicine, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Nijmegen, NetherlandsBackground: The etiology of cerebral small vessel disease (SVD) remains elusive, though evidence is accumulating that inflammation contributes to its pathophysiology. We recently showed retrospectively that pro-inflammatory monocytes are associated with the long-term progression of white matter hyperintensities (WMHs). In this prospective high-frequency imaging study, we hypothesize that the incidence of SVD progression coincides with a pro-inflammatory monocyte phenotype.Methods: Individuals with SVD underwent monthly magnetic resonance imaging (MRI) for 10 consecutive months to detect SVD progression, defined as acute diffusion-weighted imaging-positive (DWI+) lesions, incident microbleeds, incident lacunes, and WMH progression. Circulating inflammatory markers were measured, cytokine production capacity of monocytes was assessed after ex vivo stimulation, and RNA sequencing was performed on isolated monocytes in a subset of participants.Results: 13 out of 35 individuals developed SVD progression (70 ± 6 years, 54% men) based on incident lesions (n = 7) and/or upper quartile WMH progression (n = 9). Circulating E-selectin concentration (p < 0.05) and the cytokine production capacity of interleukin (IL)-1β and IL-6 (p < 0.01) were higher in individuals with SVD progression. Moreover, RNA sequencing revealed a pro-inflammatory monocyte signature including genes involved in myelination, blood–brain barrier, and endothelial–leukocyte interaction.Conclusions: Circulating monocytes of individuals with progressive SVD have an inflammatory phenotype, characterized by an increased cytokine production capacity and a pro-inflammatory transcriptional signature.https://www.frontiersin.org/articles/10.3389/fcvm.2021.639361/fullcerebral small vessel diseasemagnetic resonance imaginginnate immunitymonocyteinflammation |