Evidence map›Paper›PMID 18845539›Full record

ArticleThe Journal of biological chemistry2008

A catalytic role of heparin within the extracellular matrix.

Maria Mitsi, Kimberly Forsten-Williams, Manoj Gopalakrishnan, Matthew A Nugent

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

41 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
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  6. Implications of fibrotic extracellular matrix in diabetic retinopathy.Experimental biology and medicine (Maywood, N.J.) · 2022
    Review
  7. Review
  8. Article
  9. Article
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  11. Article
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  13. Heparin-fibronectin interactions in the development of extracellular matrix insolubility.Matrix biology : journal of the International Society for Matrix Biology · 2018
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. 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

4 authors at 3 institutions in 2 countries.

Maria MitsiDepartment of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Kimberly Forsten-Williams
Manoj Gopalakrishnan
Matthew A Nugent
Boston University · USHarish-Chandra Research Institute · INVirginia Tech · US

Funding

Growth Factors in Vascular BiologyR01HL056200 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI NUGENT, MATTHEW A · 1997 to 2008
$2.7M
Elastase Injury of Pulmonary Extracellular MatrixR01HL088572 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI NUGENT, MATTHEW A · 2008 to 2012
$2.0M
NHLBI NIH HHS HL088572NHLBI NIH HHS HL56200NHLBI NIH HHS R01 HL056200NHLBI NIH HHS R01 HL088572
6 · The paper itself

Abstract

We investigated the mechanism by which heparin enhances the binding of vascular endothelial growth factor (VEGF) to the extracellular matrix protein fibronectin. In contrast to other systems, where heparin acts as a protein scaffold, we found that heparin functions catalytically to modulate VEGF binding site availability on fibronectin. By measuring the binding of VEGF and heparin to surface-immobilized fibronectin, we show that substoichiometric amounts of heparin exposed cryptic VEGF binding sites within fibronectin that remain available after heparin removal. Measurement of association and dissociation kinetics for heparin binding to fibronectin indicated that the interaction is rapid and transient. We localized the heparin-responsive element to the C-terminal 40-kDa Hep2 domain of fibronectin. A mathematical model of this catalytic process was constructed that supports a mechanism whereby the heparin-induced conformational change in fibronectin is accompanied by release of heparin. Experiments with endothelial extracellular matrix suggest that this process may also occur within biological matrices. These results indicate a novel mechanism whereby heparin catalyzes the conversion of fibronectin to an open conformation by transiently interacting with fibronectin and progressively hopping from molecule to molecule. Catalytic activation of the extracellular matrix might be an important mechanism for heparin to regulate function during normal and disease states.

Indexed as

AnimalsAnticoagulantsBinding SitesCatalysisCattleExtracellular MatrixFibronectinsHeparinHumansKineticsModels, ChemicalProtein BindingProtein Structure, TertiaryRecombinant ProteinsVascular Endothelial Growth Factor AAnticoagulantsFibronectinsHeparinRecombinant ProteinsVascular Endothelial Growth Factor A

Identifiers

PMID18845539
PMCPMC2596404
OpenAlexW2051744951

What OpenQuestion holds

Textmetadata
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.