Transcriptomic analyses reveal proinflammatory activation of human brain microvascular endothelial cells by aging-associated peptide medin and reversal by nanoliposomes.

Autor: Zhang Y; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA., Karamanova N; Phoenix Veterans Affairs Healthcare System, 650 E. Indian School Road, Phoenix, AZ, 85022, USA., Morrow KT; Phoenix Veterans Affairs Healthcare System, 650 E. Indian School Road, Phoenix, AZ, 85022, USA., Madine J; University of Liverpool, Liverpool, UK., Truran S; Phoenix Veterans Affairs Healthcare System, 650 E. Indian School Road, Phoenix, AZ, 85022, USA., Lozoya M; Midwestern University, Glendale, AZ, USA., Weissig V; Midwestern University, Glendale, AZ, USA., Li M; Phoenix Veterans Affairs Healthcare System, 650 E. Indian School Road, Phoenix, AZ, 85022, USA.; University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA., Nikkhah M; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.; School of Biological and Health Systems Engineering, Arizona State University, Tempe, USA., Park JG; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA., Migrino RQ; Phoenix Veterans Affairs Healthcare System, 650 E. Indian School Road, Phoenix, AZ, 85022, USA. raymond.migrino@va.gov.; University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA. raymond.migrino@va.gov.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Nov 01; Vol. 13 (1), pp. 18802. Date of Electronic Publication: 2023 Nov 01.
DOI: 10.1038/s41598-023-45959-7
Abstrakt: 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 h to medin (5 µM) without or with Aβ(1-42) (2 µM) or NL (300 µg/mL), and RNA-seq with signaling pathway analyses were performed. Separately, reverse transcription polymerase chain reaction of select identified genes was done in HBMVECs treated with medin (5 µM) without or with NFκB inhibitor RO106-9920 (10 µM) or NL (300 µg/mL). Medin caused upregulation of pro-inflammatory genes that was not aggravated by Aβ42 co-treatment but reversed by NL. 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. 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 could have potential implications in the pathogenesis and treatment of vascular aging, AD and vascular dementia.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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