Evidence mapPaperPMID 25528754Full record

ArticleJournal of lipid research2015

The glycosylation-dependent interaction of perlecan core protein with LDL: implications for atherosclerosis.

Yu-Xin Xu, David Ashline, Li Liu, Carlos Tassa, Stanley Y Shaw, Katya Ravid, Matthew D Layne, Vernon Reinhold, Phillips W Robbins

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Extracellular matrix dynamics in vascular remodeling.American journal of physiology. Cell physiology · 2020
    Review
  7. Review
  8. The heparan sulfate proteoglycan grip on hyperlipidemia and atherosclerosis.Matrix biology : journal of the International Society for Matrix Biology · 2018
    Review
  9. Article
  10. Article
  11. Analysis of Apolipoprotein B Protein of Circulating Multiple-Modified Low-Density Lipoprotein.The International journal of angiology : official publication of the International College of Angiology, Inc · 2017
    Article
  12. A current view of perlecan in physiology and pathology: A mosaic of functions.Matrix biology : journal of the International Society for Matrix Biology · 2017
    Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Proteoglycan form and function: A comprehensive nomenclature of proteoglycans.Matrix biology : journal of the International Society for Matrix Biology · 2015
    Review
  18. Review
  19. Article
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

9 authors at 4 institutions in 1 country.

Yu-Xin XuCenter for Human Genetic Research and Cardiovascular Research CenterMassachusetts General Hospital, Boston, MA 02114.
David AshlineThe Glycomics Center, University of New Hampshire, Durham, NH 03824.
Li LiuDepartment of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA 02118.
Carlos TassaCenter for Systems Biology, Massachusetts General Hospital, Boston, MA 02114.
Stanley Y ShawCenter for Systems Biology, Massachusetts General Hospital, Boston, MA 02114.
Katya RavidDepartments of Medicine Boston University School of Medicine, Boston, MA 02118 Biochemistry, Boston University School of Medicine, Boston, MA 02118.
Matthew D LayneBiochemistry, Boston University School of Medicine, Boston, MA 02118.
Vernon ReinholdThe Glycomics Center, University of New Hampshire, Durham, NH 03824.
Phillips W RobbinsDepartment of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA 02118.
Boston University · USMassachusetts General Hospital · USUniversity of New Hampshire · USCenter for Systems Biology · US

Funding

NHLBI NIH HHS HHSN268201000044CNHLBI NIH HHS P01 HL107146PHS HHS HHSN268201000044C
6 · The paper itself

Abstract

Perlecan is a major heparan sulfate (HS) proteoglycan in the arterial wall. Previous studies have linked it to atherosclerosis. Perlecan contains a core protein and three HS side chains. Its core protein has five domains (DI-DV) with disparate structures and DII is highly homologous to the ligand-binding portion of LDL receptor (LDLR). The functional significance of this domain has been unknown. Here, we show that perlecan DII interacts with LDL. Importantly, the interaction largely relies on O-linked glycans that are only present in the secreted DII. Among the five repeat units of DII, most of the glycosylation sites are from the second unit, which is highly divergent and rich in serine and threonine, but has no cysteine residues. Interestingly, most of the glycans are capped by the negatively charged sialic acids, which are critical for LDL binding. We further demonstrate an additive effect of HS and DII on LDL binding. Unlike LDLR, which directs LDL uptake through endocytosis, this study uncovers a novel feature of the perlecan LDLR-like DII in receptor-mediated lipoprotein retention, which depends on its glycosylation. Thus, perlecan glycosylation may play a role in the early LDL retention during the development of atherosclerosis.

Indexed as

AnimalsAtherosclerosisCell LineChlorocebus aethiopsCOS CellsGlycosylationHeLa CellsHeparan Sulfate ProteoglycansHumansImmunohistochemistryLipoproteins, LDLMicroscopy, ConfocalMutagenesis, Site-DirectedN-Acetylneuraminic AcidRatsReceptors, LDLHeparan Sulfate ProteoglycansLipoproteins, LDLN-Acetylneuraminic AcidperlecanReceptors, LDLlow density lipoproteinlow density lipoprotein receptorsialic acid

Identifiers

PMID25528754
PMCPMC4306681
OpenAlexW2053410574

What Socratic 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 Socratic graph.