Evidence map›Paper›PMID 27087439›Full record

ArticleJournal of lipid research2016

Lipotoxic brain microvascular injury is mediated by activating transcription factor 3-dependent inflammatory and oxidative stress pathways.

Hnin Hnin Aung, Robin Altman, Tun Nyunt, Jeffrey Kim, Saivageethi Nuthikattu, Madhu Budamagunta, John C Voss, Dennis Wilson, John C Rutledge, Amparo C Villablanca

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

27 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Lipolysis products from triglyceride-rich lipoproteins induce stress protein ATF3 in osteoblasts.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024
    Article
  6. Article
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  8. Review
  9. Article
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  15. Mechanisms of Atherosclerosis Induced by Postprandial Lipemia.Frontiers in cardiovascular medicine · 2021
    Review
  16. Article
  17. Article
  18. Review
  19. Article
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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

10 authors at 1 institution in 1 country.

Hnin Hnin AungDivision of Cardiovascular Medicine, Department of Internal Medicine School of Medicine.
Robin AltmanDivision of Cardiovascular Medicine, Department of Internal Medicine School of Medicine.
Tun NyuntDivision of Cardiovascular Medicine, Department of Internal Medicine School of Medicine.
Jeffrey KimDivision of Cardiovascular Medicine, Department of Internal Medicine School of Medicine.
Saivageethi NuthikattuDivision of Cardiovascular Medicine, Department of Internal Medicine School of Medicine.
Madhu BudamaguntaDepartment of Biochemistry and Molecular Medicine, School of Medicine.
John C VossDepartment of Biochemistry and Molecular Medicine, School of Medicine.
Dennis WilsonDepartment of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616.
John C RutledgeDivision of Cardiovascular Medicine, Department of Internal Medicine School of Medicine.
Amparo C VillablancaDivision of Cardiovascular Medicine, Department of Internal Medicine School of Medicine avillablanca@ucdavis.edu.
University of California, Davis · US

Funding

Mouse Metabolic Phenotyping Center (MMPC) at UC DavisU2CDK092993 · NIDDK · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2016 to 2021
$5.9M
Mouse Metabolic Phenotyping Center (MMPC) at UC DavisU24DK092993 · NIDDK · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2011 to 2015
$4.1M
Interactions of Lipoproteins with the Vascular WallR01HL055667 · NHLBI · UNIVERSITY OF CALIFORNIA DAVIS · PI RUTLEDGE, JOHN CALVERT · 1996 to 2010
$2.8M
Brain Microvascular Determinants of Alzheimers DiseaseR01AG039094 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI RUTLEDGE, JOHN CALVERT · 2010 to 2014
$2.1M
Role of lipid droplets in neurovascular inflammationR01AG045541 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI RUTLEDGE, JOHN CALVERT, VILLABLANCA, AMPARO C · 2014 to 2018
$2.0M
NIA NIH HHS R01 AG039094NIA NIH HHS R01 AG045541NIDDK NIH HHS U24 DK092993NIDDK NIH HHS U2C DK092993
6 · The paper itself

Abstract

Dysfunction of the cerebrovasculature plays an important role in vascular cognitive impairment (VCI). Lipotoxic injury of the systemic endothelium in response to hydrolyzed triglyceride-rich lipoproteins (TGRLs; TGRL lipolysis products) or a high-fat Western diet (WD) suggests similar mechanisms may be present in brain microvascular endothelium. We investigated the hypothesis that TGRL lipolysis products cause lipotoxic injury to brain microvascular endothelium by generating increased mitochondrial superoxide radical generation, upregulation of activating transcription factor 3 (ATF3)-dependent inflammatory pathways, and activation of cellular oxidative stress and apoptotic pathways. Human brain microvascular endothelial cells were treated with human TGRL lipolysis products that induced intracellular lipid droplet formation, mitochondrial superoxide generation, ATF3-dependent transcription of proinflammatory, stress response, and oxidative stress genes, as well as activation of proapoptotic cascades. Male apoE knockout mice were fed a high-fat/high-cholesterol WD for 2 months, and brain microvessels were isolated by laser capture microdissection. ATF3 gene transcription was elevated 8-fold in the hippocampus and cerebellar brain region of the WD-fed animals compared with chow-fed control animals. The microvascular injury phenotypes observed in vitro and in vivo were similar. ATF3 plays an important role in mediating brain microvascular responses to acute and chronic lipotoxic injury and may be an important preventative and therapeutic target for endothelial dysfunction in VCI.

Indexed as

Activating Transcription Factor 3AnimalsCerebellumCerebrovascular TraumaCognitive DysfunctionDiet, High-FatDiet, WesternEndothelium, VascularHippocampusHumansInflammationLipoproteinsMiceOxidative StressSignal TransductionTriglyceridesActivating Transcription Factor 3ATF3 protein, humanLipoproteinslipoprotein triglycerideTriglyceridescell signalingcerebrovascular circulationdiet and dietary lipidsendothelial cellsgene expressioninflammationlipolysismitochondriareactive oxygen speciestriglyceride-rich lipoproteins

Identifiers

PMID27087439
PMCPMC4878181
OpenAlexW2339463430

What Socratic holds

Textmetadata
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 Socratic graph.