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Transcriptomic Analyses Reveal Proinflammatory Activation of Human Brain Microvascular Endothelial Cells by Aging-Associated Peptide Medin and Reversal by Nanoliposomes

ABSTRACT: Medin is a common vascular amyloidogenic peptide recently implicated in Alzheimer’s disease (AD) and vascular dementia and its pathology remains unknown. We aim to identify changes in transcriptomic profiles and pathways in human brain microvascular endothelial cells (HBMVECs) exposed to medin, compare that to exposure to β-amyloid (Aβ) and evaluate protection by monosialoganglioside-containing nanoliposomes (NL). HBMVECs were exposed for 20 hours to medin (5 µM) without or with Aβ(1-42) (2 µM) or NL (300 µg/mL), and RNA-seq was performed. Pathway analysis on differentially expressed genes revealed multiple pro-inflammatory signaling pathways, such as the tumor necrosis factor (TNF) and the nuclear factor-κB (NFkB) signaling pathways, were affected specifically by medin treatment. Reverse transcription polymerase chain reaction of select identified genes was done in HBMVECs treated with medin (5µM) without or with NFκB inhibitor RO106-9920 (10 µM) or NL (300 µg/mL). Medin caused upregulation of pro-inflammatory genes associated with TNF and NFκB signaling that was not aggravated by Aβ42 co-treatment but reversed by NL. RO106-9920 and NL reduced medin-induced pro-inflammatory activation. Medin induced endothelial cell pro-inflammatory signaling in part via NFκB that was reversed by NL. This has potential implications in the pathogenesis and treatment of vascular aging, AD and vascular dementia.

ORGANISM(S): Homo sapiens

PROVIDER: GSE235915 | GEO | 2023/06/27

REPOSITORIES: GEO

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