Evidence map›Paper›PMID 23162016›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2013

Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression.

Miry Blich, Amnon Golan, Gil Arvatz, Anat Sebbag, Itay Shafat, Edmond Sabo, Victoria Cohen-Kaplan, Sirouch Petcherski, Shani Avniel-Polak, Amnon Eitan and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

74 citing papers in PubMed, 128 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Role of heparanase in pulmonary hypertension.Frontiers in pharmacology · 2023
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review

14 more citing papers are in PubMed but not listed here.

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

16 authors at 1 institution in 1 country.

Miry BlichDepartment of Cardiology and Pathology, Rambam Health Care Campus, Haifa, Israel.
Amnon Golan
Gil Arvatz
Anat Sebbag
Itay Shafat
Edmond Sabo
Victoria Cohen-Kaplan
Sirouch Petcherski
Shani Avniel-Polak
Amnon Eitan
Haim Hammerman
Doron Aronson
Elena Axelman
Neta Ilan
Gabriel Nussbaum
Israel Vlodavsky
Rambam Health Care Campus · IL

Funding

Regulation of heparanase in cancer progressionR01CA106456 · NCI · TECHNION-ISRAEL INSTITUTE OF TECHNOLOGY · PI VLODAVSKY, ISRAEL · 2004 to 2013
$1.7M
NCI NIH HHS CA106456NCI NIH HHS R01 CA106456
6 · The paper itself

Abstract

objectiveFactors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages. METHODS AND

resultsHighly purified heparanase was added to mouse peritoneal macrophages and macrophage-like J774 cells, and the levels of tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 were evaluated by ELISA. Gene expression was determined by RT-PCR. Cells collected from Toll-like receptor-2 and Toll-like receptor-4 knockout mice were evaluated similarly. Heparanase levels in the plasma of patients with acute myocardial infarction, stable angina, and healthy subjects were determined by ELISA. Immunohistochemistry was applied to detect the expression of heparanase in control specimens and specimens of patients with stable angina or acute myocardial infarction. Addition or overexpression of heparanase variants resulted in marked increase in tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 levels. Mouse peritoneal macrophages harvested from Toll-like receptor-2 or Toll-like receptor-4 knockout mice were not activated by heparanase. Plasma heparanase level was higher in patients with acute myocardial infarction, compared with patients with stable angina and healthy subjects. Pathologic coronary specimens obtained from vulnerable plaques showed increased heparanase staining compared with specimens of stable plaque and controls.

conclusionsHeparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression toward vulnerability.

Indexed as

Macrophage ActivationAngina, StableAnimalsAtherosclerosisCell LineChemokine CCL2Coronary Artery DiseaseDisease ProgressionEnzyme-Linked Immunosorbent AssayGene Expression RegulationGlucuronidaseHeparanaseHumansImmunohistochemistryInterleukin-1Macrophages, PeritonealCcl2 protein, mouseChemokine CCL2GlucuronidaseHeparanaseInterleukin-1Matrix Metalloproteinase 9Mmp9 protein, mouseTlr2 protein, mouseTlr4 protein, mouseToll-Like Receptor 2Toll-Like Receptor 4Tumor Necrosis Factor-alpha

Identifiers

PMID23162016
PMCPMC3548034
OpenAlexW2108684523

What OpenQuestion holds

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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.