Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans

Abstract We test the hypothesis that endothelial cells adopt an inflammatory phenotype in functionally intact aged human subjects with radiographic evidence of white matter hyperintensity (WMH) suggestive of small cerebrovascular disease. Components of all three complement effector pathways and regu...

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Autores principales:	F. M. Elahi, D. Harvey, M. Altendahl, N. Brathaban, N. Fernandes, K. B. Casaletto, A. M. Staffaroni, P. Maillard, J. D. Hinman, B. L. Miller, C. DeCarli, J. H. Kramer, E. J. Goetzl
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c2b0d26e6a324690b574d146c5796722
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spelling	oai:doaj.org-article:c2b0d26e6a324690b574d146c57967222021-12-02T15:07:47ZElevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans10.1038/s41598-021-91759-22045-2322https://doaj.org/article/c2b0d26e6a324690b574d146c57967222021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91759-2https://doaj.org/toc/2045-2322Abstract We test the hypothesis that endothelial cells adopt an inflammatory phenotype in functionally intact aged human subjects with radiographic evidence of white matter hyperintensity (WMH) suggestive of small cerebrovascular disease. Components of all three complement effector pathways and regulatory proteins were quantified in extracts of plasma endothelial-derived exosomes (EDE) of 11 subjects (age 70–82) with and 15 without evidence of WMH on MRI. Group differences and associations with plasma markers of immune activation (IL6, ICAM1), cognition and neuroimaging were calculated via regression modelling. EDE complement factors within the alternative and classical pathways were found to be higher and regulatory proteins lower in subjects with WMH. EDE levels of some complement components demonstrated significant associations with cognitive slowing and elevated systolic blood pressure. The inhibitor of the membrane attack complex, CD46, showed a significant positive association with cerebral grey matter volume. Plasma inflammatory markers, IL6 and ICAM1, were positively associated with EDE levels of several complement components. These findings provide the first in vivo evidence of the association of endothelial cell inflammation with white matter disease, age-associated cognitive changes, and brain degeneration in functionally normal older individuals. Future endothelial biomarker development may permit recognition of early or preclinical stages of vascular contributions to cognitive impairment and dementia.F. M. ElahiD. HarveyM. AltendahlN. BrathabanN. FernandesK. B. CasalettoA. M. StaffaroniP. MaillardJ. D. HinmanB. L. MillerC. DeCarliJ. H. KramerE. J. GoetzlNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q F. M. Elahi D. Harvey M. Altendahl N. Brathaban N. Fernandes K. B. Casaletto A. M. Staffaroni P. Maillard J. D. Hinman B. L. Miller C. DeCarli J. H. Kramer E. J. Goetzl Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans
description	Abstract We test the hypothesis that endothelial cells adopt an inflammatory phenotype in functionally intact aged human subjects with radiographic evidence of white matter hyperintensity (WMH) suggestive of small cerebrovascular disease. Components of all three complement effector pathways and regulatory proteins were quantified in extracts of plasma endothelial-derived exosomes (EDE) of 11 subjects (age 70–82) with and 15 without evidence of WMH on MRI. Group differences and associations with plasma markers of immune activation (IL6, ICAM1), cognition and neuroimaging were calculated via regression modelling. EDE complement factors within the alternative and classical pathways were found to be higher and regulatory proteins lower in subjects with WMH. EDE levels of some complement components demonstrated significant associations with cognitive slowing and elevated systolic blood pressure. The inhibitor of the membrane attack complex, CD46, showed a significant positive association with cerebral grey matter volume. Plasma inflammatory markers, IL6 and ICAM1, were positively associated with EDE levels of several complement components. These findings provide the first in vivo evidence of the association of endothelial cell inflammation with white matter disease, age-associated cognitive changes, and brain degeneration in functionally normal older individuals. Future endothelial biomarker development may permit recognition of early or preclinical stages of vascular contributions to cognitive impairment and dementia.
format	article
author	F. M. Elahi D. Harvey M. Altendahl N. Brathaban N. Fernandes K. B. Casaletto A. M. Staffaroni P. Maillard J. D. Hinman B. L. Miller C. DeCarli J. H. Kramer E. J. Goetzl
author_facet	F. M. Elahi D. Harvey M. Altendahl N. Brathaban N. Fernandes K. B. Casaletto A. M. Staffaroni P. Maillard J. D. Hinman B. L. Miller C. DeCarli J. H. Kramer E. J. Goetzl
author_sort	F. M. Elahi
title	Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans
title_short	Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans
title_full	Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans
title_fullStr	Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans
title_full_unstemmed	Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans
title_sort	elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c2b0d26e6a324690b574d146c5796722
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Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans

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