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

Heraliyawala K Dias, Helen R Griffiths, Kiran Shabir, Caroline L.R. Brown, Maria Cristina Polidori

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)1009-1017
JournalJournal of Alzheimer's disease
Volume64
Issue number3
DOIs
Publication statusPublished - 3 Jul 2018

Fingerprint

MicroRNAs
Dementia
Endothelial Cells
Cytokines
Oxidation-Reduction
Alzheimer Disease
Genes
Genome-Wide Association Study
Nerve Growth Factors
27-hydroxycholesterol
Blood-Brain Barrier
Lipid Metabolism
Single Nucleotide Polymorphism
Glutathione
Interleukin-6
Anti-Inflammatory Agents
Inflammation
Lipids
Cell Line
Brain

Bibliographical note

© 2018 IOS Press. The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-180201

Cite this

Dias, Heraliyawala K ; Griffiths, Helen R ; Shabir, Kiran ; Brown, Caroline L.R. ; Polidori, Maria Cristina. / miRNA 933 Expression by Endothelial Cells is Increased by 27-Hydroxycholesterol and is More Prevalent in Plasma from Dementia Patients. In: Journal of Alzheimer's disease. 2018 ; Vol. 64, No. 3. pp. 1009-1017.
@article{924f7664224247fbad69ac3819f756eb,
title = "miRNA 933 Expression by Endothelial Cells is Increased by 27-Hydroxycholesterol and is More Prevalent in Plasma from Dementia Patients",
abstract = "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.",
author = "Dias, {Heraliyawala K} and Griffiths, {Helen R} and Kiran Shabir and Brown, {Caroline L.R.} and Polidori, {Maria Cristina}",
note = "{\circledC} 2018 IOS Press. The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-180201",
year = "2018",
month = "7",
day = "3",
doi = "10.3233/JAD-180201",
language = "English",
volume = "64",
pages = "1009--1017",
journal = "Journal of Alzheimer's disease",
issn = "1387-2877",
publisher = "IOS",
number = "3",

}

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.; Polidori, Maria Cristina.

In: Journal of Alzheimer's disease, Vol. 64, No. 3, 03.07.2018, p. 1009-1017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - miRNA 933 Expression by Endothelial Cells is Increased by 27-Hydroxycholesterol and is More Prevalent in Plasma from Dementia Patients

AU - Dias, Heraliyawala K

AU - Griffiths, Helen R

AU - Shabir, Kiran

AU - Brown, Caroline L.R.

AU - Polidori, Maria Cristina

N1 - © 2018 IOS Press. The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-180201

PY - 2018/7/3

Y1 - 2018/7/3

N2 - 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.

AB - 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.

UR - https://content.iospress.com/articles/journal-of-alzheimers-disease/jad180201

U2 - 10.3233/JAD-180201

DO - 10.3233/JAD-180201

M3 - Article

VL - 64

SP - 1009

EP - 1017

JO - Journal of Alzheimer's disease

JF - Journal of Alzheimer's disease

SN - 1387-2877

IS - 3

ER -