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

Dias, Heraliyawala K, Griffiths, Helen R, Shabir, Kiran, Brown, Caroline L.R. and Polidori, Maria Cristina (2018). miRNA 933 Expression by Endothelial Cells is Increased by 27-Hydroxycholesterol and is More Prevalent in Plasma from Dementia Patients. Journal of Alzheimer's disease, 64 (3), pp. 1009-1017.


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: Life & Health Sciences > Psychology
Life & Health Sciences
Life & Health Sciences > Chronic and Communicable Conditions
Life & Health Sciences > Biosciences
Additional Information: © 2018 IOS Press. The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-180201
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Related URLs: https://content ... sease/jad180201 (Publisher URL)
Published Date: 2018-07-03
Authors: Dias, Heraliyawala K ( 0000-0002-6620-8221)
Griffiths, Helen R
Shabir, Kiran
Brown, Caroline L.R.
Polidori, Maria Cristina



Version: Accepted Version

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