miRNA 933 Expression by Endothelial Cells is Increased by 27-Hydroxycholesterol and is More Prevalent in Plasma from Dementia Patients


Alzheimer’s disease (AD) etiology is complex; gene and environmental risk factors may interact to predispose to disease. From single nucleotide polymorphism analyses and genome-wide association studies, a number of candidate risk genes for the onset of AD have been identified and cluster around lipid metabolism and inflammation. We hypothesized that endothelial cells which line the blood-brain barrier are likely to be critical mediators of systemic metabolism within the brain. Therefore, we have studied the effect of 27 hydroxycholesterol (27-OHC) on microvascular endothelial cell (HMVEC) redox state, inflammatory cytokine secretion, and microRNA (miR) expression. Using a transwell method, we have studied directional secretion profiles for the proinflammatory cytokines TNFα and IL-6 and confirmed that 27-OHC induces discrete and directional inflammatory molecular signatures from HMVEC. The lipids caused depletion of cellular glutathione and cytokine secretion is HMVEC-redox state-dependent. Discovery miR expression changes in HMVEC with and without 27-OHC treatment was undertaken. We selected three genes for further analysis by qPCR; miR-144 and 146 expression, which are anti-inflammatory and redox regulating modulators, were not affected significantly by 27-OHC. However, increased expression of a putative neurotrophic regulatory factor miR933 in HMVEC with 27-OHC was confirmed by qPCR. In plasma from patients with dementia, all three miR were found at significantly elevated levels compared to healthy older adults. These data highlight that 27-OHC has an important regulatory effect on endothelial microvascular cells to increase expression of a miR (–933) and secretion of inflammatory cytokines that are elevated in plasma from dementia patients.

Publication DOI: https://doi.org/10.3233/JAD-180201
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences
Additional Information: © 2018 IOS Press. The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-180201
Publication ISSN: 1875-8908
Last Modified: 01 Apr 2024 07:26
Date Deposited: 04 Jul 2018 09:35
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Related URLs: https://content ... sease/jad180201 (Publisher URL)
PURE Output Type: Article
Published Date: 2018-07-03
Accepted Date: 2018-05-20
Authors: Dias, Heraliyawala K (ORCID Profile 0000-0002-6620-8221)
Griffiths, Helen R
Shabir, Kiran
Brown, Caroline L.R.
Polidori, Maria Cristina



Version: Accepted Version

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