Pulsatile stretch as a novel modulator of amyloid precursor protein processing and associated inflammatory markers in human cerebral endothelial cells

Sumudu V. S. Gangoda, Bhargava Avadhanam, Nurul F. Jufri, Eun Hwa Sohn, Mark Butlin*, Vivek Gupta, Roger Chung, Alberto P. Avolio

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
28 Downloads (Pure)

Abstract

Amyloid β (Aβ) deposition is a hallmark of Alzheimer's disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.

Original languageEnglish
Article number1689
Pages (from-to)1-10
Number of pages10
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 26 Jan 2018

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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