Evidence map›Paper›PMID 33684447›Full record

ArticleThe Journal of biological chemistry

Macrophages bind LDL using heparan sulfate and the perlecan protein core.

Chun-Yi Ng, John M Whitelock, Helen Williams, Ha Na Kim, Heather J Medbury, Megan S Lord

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

17 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Heparan Sulfate Proteoglycans in Immunity.Proteoglycan research · 2026
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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

6 authors at 2 institutions in 1 country.

Chun-Yi NgGraduate School of Biomedical Engineering, UNSW Sydney, Sydney, New South Wales, Australia; Vascular Biology Research Centre, Department of Surgery, Westmead Hospital, Westmead, New South Wales, Australia; The University of Sydney, Westmead Clinical School, Westmead, New South Wales, Australia.
John M WhitelockGraduate School of Biomedical Engineering, UNSW Sydney, Sydney, New South Wales, Australia.
Helen WilliamsVascular Biology Research Centre, Department of Surgery, Westmead Hospital, Westmead, New South Wales, Australia; The University of Sydney, Westmead Clinical School, Westmead, New South Wales, Australia.
Ha Na KimGraduate School of Biomedical Engineering, UNSW Sydney, Sydney, New South Wales, Australia.
Heather J MedburyVascular Biology Research Centre, Department of Surgery, Westmead Hospital, Westmead, New South Wales, Australia; The University of Sydney, Westmead Clinical School, Westmead, New South Wales, Australia. Electronic address: heather.medbury@sydney.edu.au.
Megan S LordGraduate School of Biomedical Engineering, UNSW Sydney, Sydney, New South Wales, Australia. Electronic address: m.lord@unsw.edu.au.
The University of Sydney · AUUNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The retention of low-density lipoprotein (LDL) is a key process in the pathogenesis of atherosclerosis and largely mediated via smooth-muscle cell-derived extracellular proteoglycans including the glycosaminoglycan chains. Macrophages can also internalize lipids via complexes with proteoglycans. However, the role of polarized macrophage-derived proteoglycans in binding LDL is unknown and important to advance our understanding of the pathogenesis of atherosclerosis. We therefore examined the identity of proteoglycans, including the pendent glycosaminoglycans, produced by polarized macrophages to gain insight into the molecular basis for LDL binding. Using the quartz crystal microbalance with dissipation monitoring technique, we established that classically activated macrophage (M1)- and alternatively activated macrophage (M2)-derived proteoglycans bind LDL via both the protein core and heparan sulfate (HS) in vitro. Among the proteoglycans secreted by macrophages, we found perlecan was the major protein core that bound LDL. In addition, we identified perlecan in the necrotic core as well as the fibrous cap of advanced human atherosclerotic lesions in the same regions as HS and colocalized with M2 macrophages, suggesting a functional role in lipid retention in vivo. These findings suggest that macrophages may contribute to LDL retention in the plaque by the production of proteoglycans; however, their contribution likely depends on both their phenotype within the plaque and the presence of enzymes, such as heparanase, that alter the secreted protein structure.

Indexed as

AtherosclerosisCells, CulturedHeparan SulfateHeparan Sulfate ProteoglycansHumansLipoproteins, LDLMacrophagesHeparan SulfateHeparan Sulfate ProteoglycansLipoproteins, LDLperlecanatherosclerosischondroitin sulfateextracellular matrixglycosaminoglycanheparan sulfatelow-density lipoproteinmacrophageperlecanproteoglycanquartz crystal microbalance

Identifiers

PMID33684447
PMCPMC8027565
OpenAlexW3135052526

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.