Cargando…

Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma

The pathogenesis of cerebral small vessel disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study, we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describ...

Descripción completa

Detalles Bibliográficos
Autores principales: Cifù, Adriana, Janes, Francesco, Mio, Catia, Domenis, Rossana, Pessa, Maria Elena, Garbo, Riccardo, Curcio, Francesco, Valente, Mariarosaria, Fabris, Martina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10669613/
https://www.ncbi.nlm.nih.gov/pubmed/38002055
http://dx.doi.org/10.3390/biomedicines11113055
_version_ 1785149242850934784
author Cifù, Adriana
Janes, Francesco
Mio, Catia
Domenis, Rossana
Pessa, Maria Elena
Garbo, Riccardo
Curcio, Francesco
Valente, Mariarosaria
Fabris, Martina
author_facet Cifù, Adriana
Janes, Francesco
Mio, Catia
Domenis, Rossana
Pessa, Maria Elena
Garbo, Riccardo
Curcio, Francesco
Valente, Mariarosaria
Fabris, Martina
author_sort Cifù, Adriana
collection PubMed
description The pathogenesis of cerebral small vessel disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study, we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from three groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD-related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the only pathway altered in CTRL-related treatment. Indeed, 36 different biological processes turned out to be deregulated after PT treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients’ plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease.
format Online
Article
Text
id pubmed-10669613
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-106696132023-11-14 Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma Cifù, Adriana Janes, Francesco Mio, Catia Domenis, Rossana Pessa, Maria Elena Garbo, Riccardo Curcio, Francesco Valente, Mariarosaria Fabris, Martina Biomedicines Article The pathogenesis of cerebral small vessel disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study, we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from three groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD-related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the only pathway altered in CTRL-related treatment. Indeed, 36 different biological processes turned out to be deregulated after PT treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients’ plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease. MDPI 2023-11-14 /pmc/articles/PMC10669613/ /pubmed/38002055 http://dx.doi.org/10.3390/biomedicines11113055 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cifù, Adriana
Janes, Francesco
Mio, Catia
Domenis, Rossana
Pessa, Maria Elena
Garbo, Riccardo
Curcio, Francesco
Valente, Mariarosaria
Fabris, Martina
Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma
title Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma
title_full Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma
title_fullStr Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma
title_full_unstemmed Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma
title_short Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma
title_sort brain endothelial cells activate neuroinflammatory pathways in response to early cerebral small vessel disease (csvd) patients’ plasma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10669613/
https://www.ncbi.nlm.nih.gov/pubmed/38002055
http://dx.doi.org/10.3390/biomedicines11113055
work_keys_str_mv AT cifuadriana brainendothelialcellsactivateneuroinflammatorypathwaysinresponsetoearlycerebralsmallvesseldiseasecsvdpatientsplasma
AT janesfrancesco brainendothelialcellsactivateneuroinflammatorypathwaysinresponsetoearlycerebralsmallvesseldiseasecsvdpatientsplasma
AT miocatia brainendothelialcellsactivateneuroinflammatorypathwaysinresponsetoearlycerebralsmallvesseldiseasecsvdpatientsplasma
AT domenisrossana brainendothelialcellsactivateneuroinflammatorypathwaysinresponsetoearlycerebralsmallvesseldiseasecsvdpatientsplasma
AT pessamariaelena brainendothelialcellsactivateneuroinflammatorypathwaysinresponsetoearlycerebralsmallvesseldiseasecsvdpatientsplasma
AT garboriccardo brainendothelialcellsactivateneuroinflammatorypathwaysinresponsetoearlycerebralsmallvesseldiseasecsvdpatientsplasma
AT curciofrancesco brainendothelialcellsactivateneuroinflammatorypathwaysinresponsetoearlycerebralsmallvesseldiseasecsvdpatientsplasma
AT valentemariarosaria brainendothelialcellsactivateneuroinflammatorypathwaysinresponsetoearlycerebralsmallvesseldiseasecsvdpatientsplasma
AT fabrismartina brainendothelialcellsactivateneuroinflammatorypathwaysinresponsetoearlycerebralsmallvesseldiseasecsvdpatientsplasma