Evidence map›Paper›PMID 28830501›Full record

ArticleMolecular neurodegeneration2017

High-density lipoproteins suppress Aβ-induced PBMC adhesion to human endothelial cells in bioengineered vessels and in monoculture.

Jérôme Robert, Emily B Button, Sophie Stukas, Guilaine K Boyce, Ebrima Gibbs, Catherine M Cowan, Megan Gilmour, Wai Hang Cheng, Sonja K Soo, Brian Yuen and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.

  1. Pooled it
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  7. Article
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  9. Midlife lipid and glucose levels are associated with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
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  14. Toward three-dimensionalNeural regeneration research · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Jérôme RobertDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.ORCID 0000-0002-2847-9362
Emily B ButtonDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Sophie StukasDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Guilaine K BoyceDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Ebrima GibbsDjavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
Catherine M CowanDepartment of Zoology, University of British Columbia, Vancouver, BC, V6T 2B5, Canada.
Megan GilmourDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Wai Hang ChengDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Sonja K SooDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Brian YuenDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Arvin BahrabadiDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Kevin KangDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Iva KulicDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Gordon FrancisDepartment of Medicine, University of British Columbia, Vancouver, BC, V6Z 1Y6, Canada.
Neil CashmanDjavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
Cheryl L WellingtonDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. wcheryl@mail.ubc.ca.
University of British Columbia · CAUniversity of British Columbia Hospital · CA

Funding

CIHR 148,883Swiss National Science Foundation 155048
6 · The paper itself

Abstract

backgroundAlzheimer's Disease (AD), characterized by accumulation of beta-amyloid (Aβ) plaques in the brain, can be caused by age-related failures to clear Aβ from the brain through pathways that involve the cerebrovasculature. Vascular risk factors are known to increase AD risk, but less is known about potential protective factors. We hypothesize that high-density lipoproteins (HDL) may protect against AD, as HDL have vasoprotective properties that are well described for peripheral vessels. Epidemiological studies suggest that HDL is associated with reduced AD risk, and animal model studies support a beneficial role for HDL in selectively reducing cerebrovascular amyloid deposition and neuroinflammation. However, the mechanism by which HDL may protect the cerebrovascular endothelium in the context of AD is not understood.

methodsWe used peripheral blood mononuclear cell adhesion assays in both a highly novel three dimensional (3D) biomimetic model of the human vasculature composed of primary human endothelial cells (EC) and smooth muscle cells cultured under flow conditions, as well as in monolayer cultures of ECs, to study how HDL protects ECs from the detrimental effects of Aβ.

resultsFollowing Aβ addition to the abluminal (brain) side of the vessel, we demonstrate that HDL circulated within the lumen attenuates monocyte adhesion to ECs in this biofidelic vascular model. The mechanism by which HDL suppresses Aβ-mediated monocyte adhesion to ECs was investigated using monotypic EC cultures. We show that HDL reduces Aβ-induced PBMC adhesion to ECs independent of nitric oxide (NO) production, miR-233 and changes in adhesion molecule expression. Rather, HDL acts through scavenger receptor (SR)-BI to block Aβ uptake into ECs and, in cell-free assays, can maintain Aβ in a soluble state. We confirm the role of SR-BI in our bioengineered human vessel.

conclusionOur results define a novel activity of HDL that suppresses Aβ-mediated monocyte adhesion to the cerebrovascular endothelium.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainCells, CulturedDisease Models, AnimalEndothelial CellsHumansLeukocytes, MononuclearLipoproteins, HDLMonocytesPlaque, AmyloidAmyloid beta-PeptidesLipoproteins, HDLAlzheimer’s diseaseBeta-amyloidEndothelial cellsEngineered vesselHigh-density lipoprotein

Identifiers

PMID28830501
PMCPMC5568306
OpenAlexW2746994457

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.