Evidence map›Paper›PMID 22820644›Full record

ArticleNature medicine2012

The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis.

Eric P Schmidt, Yimu Yang, William J Janssen, Aneta Gandjeva, Mario J Perez, Lea Barthel, Rachel L Zemans, Joel C Bowman, Dan E Koyanagi, Zulma X Yunt and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 500 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
500citing papers in PubMed, 3 pooled it
19.1field-weighted citation impact, top 1% 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

500 citing papers in PubMed, 3 syntheses or guidelines pooled it, 820 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Effect of 5% albumin on endothelial glycocalyx degradation during off-pump coronary artery bypass.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2024
    Trial
  7. Trial
  8. Observational
  9. Review
  10. Endothelial Exostosin-1 Is Needed for Glycocalyx Integrity and Inflammatory Resolution in Acute Lung Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Pharmaceuticals (Basel, Switzerland) · 2026
    Article
  19. Article
  20. Article

440 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

18 authors at 4 institutions in 1 country.

Eric P SchmidtDepartment of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, Program in Translational Lung Research, University of Colorado School of Medicine, Aurora, Colorado, USA; Denver Health Medical Center, Denver, Colorado, USA. eric.schmidt@ucdenver.edu
Yimu Yang
William J Janssen
Aneta Gandjeva
Mario J Perez
Lea Barthel
Rachel L Zemans
Joel C Bowman
Dan E Koyanagi
Zulma X Yunt
Lynelle P Smith
Sara S Cheng
Katherine H Overdier
Kathy R Thompson
Mark W Geraci
Ivor S Douglas
David B Pearse
Rubin M Tuder
University of Colorado Denver · USNational Jewish Health · USDenver Health Medical Center · USJohns Hopkins Medicine · US

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025780 · NCRR · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2008 to 2011
$61.3M
Macrophage Apoptosis in Resolution of Acute Lung InjuryR01HL109517 · NHLBI · NATIONAL JEWISH HEALTH · PI JANSSEN, WILLIAM · 2012 to 2017
$3.1M
Common targeting of the prostacyclin-PPARy axis in COPD and lung cancerR01CA164780 · NCI · UNIVERSITY OF COLORADO DENVER · PI TUDER, RUBIN M. · 2011 to 2014
$2.3M
RTP-801 in Cigarette Smoke-EmphysemaR01ES016285 · NIEHS · UNIVERSITY OF COLORADO DENVER · PI TUDER, RUBIN M. · 2011 to 2015
$1.6M
Molecular Physiology Core Applied to Acute Lung InjuryP30HL101295 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI GERACI, MARK W · 2009 to 2010
$1.0M
Pulmonary endothelial glycocalyx degradation causes ARDS during sepsisK08HL105538 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI SCHMIDT, ERIC PETER · 2011 to 2015
$644k
Role of Beta-catenin in Epithelial Repair in Acute Lung InjuryK08HL103772 · NHLBI · NATIONAL JEWISH HEALTH · PI ZEMANS, RACHEL LYNNE · 2010 to 2014
$626k
NCI NIH HHS R01 CA164780NCRR NIH HHS UL1 RR025780NHLBI NIH HHS K08 HL103772NHLBI NIH HHS K08 HL105538NHLBI NIH HHS P30 HL101295NHLBI NIH HHS R01 HL109517NIEHS NIH HHS R01 ES016285PHS HHS P01-NHLBI 085609
6 · The paper itself

Abstract

Sepsis, a systemic inflammatory response to infection, commonly progresses to acute lung injury (ALI), an inflammatory lung disease with high morbidity. We postulated that sepsis-associated ALI is initiated by degradation of the pulmonary endothelial glycocalyx, leading to neutrophil adherence and inflammation. Using intravital microscopy, we found that endotoxemia in mice rapidly induced pulmonary microvascular glycocalyx degradation via tumor necrosis factor-α (TNF-α)-dependent mechanisms. Glycocalyx degradation involved the specific loss of heparan sulfate and coincided with activation of endothelial heparanase, a TNF-α-responsive, heparan sulfate-specific glucuronidase. Glycocalyx degradation increased the availability of endothelial surface adhesion molecules to circulating microspheres and contributed to neutrophil adhesion. Heparanase inhibition prevented endotoxemia-associated glycocalyx loss and neutrophil adhesion and, accordingly, attenuated sepsis-induced ALI and mortality in mice. These findings are potentially relevant to human disease, as sepsis-associated respiratory failure in humans was associated with higher plasma heparan sulfate degradation activity; moreover, heparanase content was higher in human lung biopsies showing diffuse alveolar damage than in normal human lung tissue.

Indexed as

Acute Lung InjuryAdoptive TransferAnimalsCell AdhesionDisease Models, AnimalEndotheliumEndotoxemiaEnzyme ActivationGene Expression RegulationGlucuronidaseGlycocalyxHeparanaseHeparan SulfateHumansIntercellular Adhesion Molecule-1Intestinal PerforationGlucuronidaseHeparanaseHeparan SulfateIntercellular Adhesion Molecule-1lipopolysaccharide, E coli O55-B5LipopolysaccharidesReceptors, Tumor Necrosis Factor, Type ITnfrsf1a protein, mouseTumor Necrosis Factor-alpha

Identifiers

PMID22820644
PMCPMC3723751
OpenAlexW2111766323

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.