Evidence map›Paper›PMID 25440058›Full record

ArticleCell metabolism2014

Reducing macrophage proteoglycan sulfation increases atherosclerosis and obesity through enhanced type I interferon signaling.

Philip L S M Gordts, Erin M Foley, Roger Lawrence, Risha Sinha, Carlos Lameda-Diaz, Liwen Deng, Ryan Nock, Christopher K Glass, Ayca Erbilgin, Aldons J Lusis and 2 more

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

Article in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

56 citing papers in PubMed, 82 citations in OpenAlex.

  1. Article
  2. Airway macrophage specific glycocalyx expression and remodeling following viral infection.Matrix biology : journal of the International Society for Matrix Biology · 2026
    Article
  3. Heparan Sulfate Proteoglycans in Immunity.Proteoglycan research · 2026
    Article
  4. Sulfated Glycosaminoglycans in Inflammation.Advances in experimental medicine and biology · 2026
    Review
  5. Article
  6. Article
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  10. 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

12 authors at 2 institutions in 1 country.

Philip L S M GordtsDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Erin M FoleyDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
Roger LawrenceDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Risha SinhaDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Carlos Lameda-DiazDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Liwen DengDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Ryan NockDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Ayca ErbilginDepartment of Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Aldons J LusisDepartment of Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Joseph L WitztumDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Jeffrey D EskoDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: jesko@ucsd.edu.
University of California, San Diego · USUniversity of California, Los Angeles · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 1985 to 2019
$50.2M
Transcriptional GenomicsP01HL088093 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2008 to 2018
$26.4M
Siglec Modulation of Inflammatory ResponsesP01HL107150 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LE, DZUNG T · 2011 to 2017
$18.0M
Transcriptional Genomics CoreP01DK074868 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K · 2007 to 2016
$16.6M
GENETIC CONTROL OF PROTEOGLYCAN METABOLISMR37GM033063 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 2000 to 2010
$3.9M
LIPID METABOLISM IN ANIMAL CELLSR01GM033063 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 1985 to 2019
$3.4M
NCI NIH HHS P30 CA023100NHLBI NIH HHS HL 088093NHLBI NIH HHS HL28481NHLBI NIH HHS HL30568NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS P01 HL088093NHLBI NIH HHS P01 HL107150NIDDK NIH HHS P01 DK074868NIGMS NIH HHS GM33063NIGMS NIH HHS R01 GM033063NIGMS NIH HHS R37 GM033063
6 · The paper itself

Abstract

Heparan sulfate proteoglycans (HSPGs) are an important constituent of the macrophage glycocalyx and extracellular microenvironment. To examine their role in atherogenesis, we inactivated the biosynthetic gene N-acetylglucosamine N-deacetylase-N-sulfotransferase 1 (Ndst1) in macrophages and crossbred the strain to Ldlr(-/-) mice. When placed on an atherogenic diet, Ldlr(-/-)Ndst1(f/f)LysMCre(+) mice had increased atherosclerotic plaque area and volume compared to Ldlr(-/-) mice. Diminished sulfation of heparan sulfate resulted in enhanced chemokine expression; increased macrophages in plaques; increased expression of ACAT2, a key enzyme in cholesterol ester storage; and increased foam cell conversion. Motif analysis of promoters of upregulated genes suggested increased type I interferon signaling, which was confirmed by elevation of STAT1 phosphorylation induced by IFN-β. The proinflammatory macrophages derived from Ndst1(f/f)LysMCre(+) mice also sensitized the animals to diet-induced obesity. We propose that macrophage HSPGs control basal activation of macrophages by maintaining type I interferon reception in a quiescent state through sequestration of IFN-β.

Indexed as

Signal TransductionAnimalsAtherosclerosisDiet, AtherogenicFemaleGene Expression RegulationHeparan Sulfate ProteoglycansInterferon Type IMacrophagesMaleMiceModels, MolecularObesitySulfotransferasesHeparan Sulfate Proteoglycansheparitin sulfotransferaseInterferon Type ISulfotransferases

Identifiers

PMID25440058
PMCPMC4254584
OpenAlexW2094767051

What OpenQuestion holds

Textmetadata
LicenceTDM
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.