Evidence map›Paper›PMID 18596265›Full record

ArticleCirculation research2008

Heparan sulfate in perlecan promotes mouse atherosclerosis: roles in lipid permeability, lipid retention, and smooth muscle cell proliferation.

Karin Tran-Lundmark, Phan-Kiet Tran, Gabrielle Paulsson-Berne, Vincent Fridén, Raija Soininen, Karl Tryggvason, Thomas N Wight, Michael G Kinsella, Jan Borén, Ulf Hedin

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Circulation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

57 citing papers in PubMed, 105 citations in OpenAlex.

  1. Article
  2. Review
  3. Modulation of host gene expression by the zinc finger antiviral protein.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. The Role of Matrix Proteins in Cardiac Pathology.International journal of molecular sciences · 2022
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. A Systems View of the Heparan Sulfate Interactome.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021
    Review
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Karin Tran-LundmarkDepartment of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, SE-17176 Stockholm, Sweden. karin.tran.lundmark@ki.se
Phan-Kiet Tran
Gabrielle Paulsson-Berne
Vincent Fridén
Raija Soininen
Karl Tryggvason
Thomas N Wight
Michael G Kinsella
Jan Borén
Ulf Hedin
Karolinska Institutet · SE

Funding

VLA-4 and VCAM-1 in Advanced AtherosclerosisP01HL018645 · NHLBI · UNIVERSITY OF WASHINGTON · PI CHAIT, ALAN · 1985 to 2010
$23.9M
NHLBI NIH HHS P01 HL018645PHS HHS 18645
6 · The paper itself

Abstract

Heparan sulfate (HS) has been proposed to be antiatherogenic through inhibition of lipoprotein retention, inflammation, and smooth muscle cell proliferation. Perlecan is the predominant HS proteoglycan in the artery wall. Here, we investigated the role of perlecan HS chains using apoE null (ApoE0) mice that were cross-bred with mice expressing HS-deficient perlecan (Hspg2(Delta3/Delta3)). Morphometry of cross-sections from aortic roots and en face preparations of whole aortas revealed a significant decrease in lesion formation in ApoE0/Hspg2(Delta3/Delta3) mice at both 15 and 33 weeks. In vitro, binding of labeled mouse triglyceride-rich lipoproteins and human LDL to total extracellular matrix, as well as to purified proteoglycans, prepared from ApoE0/Hspg2(Delta3/Delta3) smooth muscle cells was reduced. In vivo, at 20 minutes influx of human (125)I-LDL or mouse triglyceride-rich lipoproteins into the aortic wall was increased in ApoE0/Hspg2(Delta3/Delta3) mice compared to ApoE0 mice. However, at 72 hours accumulation of (125)I-LDL was similar in ApoE0/Hspg2(Delta3/Delta3) and ApoE0 mice. Immunohistochemistry of lesions from ApoE0/Hspg2(Delta3/Delta3) mice showed decreased staining for apoB and increased smooth muscle alpha-actin content, whereas accumulation of CD68-positive inflammatory cells was unchanged. We conclude that the perlecan HS chains are proatherogenic in mice, possibly through increased lipoprotein retention, altered vascular permeability, or other mechanisms. The ability of HS to inhibit smooth muscle cell growth may also influence development as well as instability of lesions.

Indexed as

Capillary PermeabilityActinsAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticAortaApolipoproteins BApolipoproteins EAtherosclerosisCD68 MoleculeCell ProliferationCrosses, GeneticDisease Models, AnimalHeparan SulfateHeparan Sulfate ProteoglycansHumansActinsAntigens, CDAntigens, Differentiation, MyelomonocyticApolipoproteins BApolipoproteins ECD68 MoleculeCD68 protein, mouseHeparan SulfateHeparan Sulfate ProteoglycansLipoproteins, LDLperlecanTriglycerides

Identifiers

PMID18596265
PMCPMC2765377
OpenAlexW2109847615

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.