Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Adriana Cifù
,
Francesco Janes
* ,
Catia Mio
ORCID logo ,
Rossana Domenis
ORCID logo ,
Maria Elena Pessa
,
Riccardo Garbo
ORCID logo ,
Francesco Curcio
,
Mariarosaria Valente
,
Martina Fabris
ORCID logo
Version 1 : Received: 1 September 2023 / Approved: 4 September 2023 / Online: 5 September 2023 (03:36:22 CEST)

A peer-reviewed article of this Preprint also exists.

Cifù, A.; Janes, F.; Mio, C.; Domenis, R.; Pessa, M.E.; Garbo, R.; Curcio, F.; Valente, M.; Fabris, M. Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma. Biomedicines 2023, 11, 3055. Cifù, A.; Janes, F.; Mio, C.; Domenis, R.; Pessa, M.E.; Garbo, R.; Curcio, F.; Valente, M.; Fabris, M. Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma. Biomedicines 2023, 11, 3055.

Abstract

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 3 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 solely pathway altered in CTRLs related treatment. Indeed, 36 different biological processes turned out to be deregulated after PTs 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.

Keywords

neuroinflammation; cytokines; endothelial dysfunction; cerebral small vessel disease

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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