Evidence map›Paper›PMID 24469066›Full record

ArticleVascular pharmacology2014

Low anticoagulant heparin blocks thrombin-induced endothelial permeability in a PAR-dependent manner.

Joyce N Gonzales, Kyung-mi Kim, Marina A Zemskova, Ruslan Rafikov, Brenten Heeke, Matthew N Varn, Stephen Black, Thomas P Kennedy, Alexander D Verin, Evgeny A Zemskov

Open access · greenAbstract read
In one paragraph

Article in Vascular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

20 citing papers in PubMed, 32 citations in OpenAlex.

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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

10 authors at 2 institutions in 1 country.

Joyce N GonzalesVascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: jgonzales@gru.edu.
Kyung-mi KimVascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: i60p68@hotmail.com.
Marina A ZemskovaVascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: mzemskova@gru.edu.
Ruslan RafikovVascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: rrafikov@gru.edu.
Brenten HeekeVascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: bheeke@gru.edu.
Matthew N VarnVascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: mvarn@gru.edu.
Stephen BlackVascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: sblack@gru.edu.
Thomas P KennedyDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: tkennedy@gru.edu.
Alexander D VerinVascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: averin@gru.edu.
Evgeny A ZemskovVascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: ezemskov@gru.edu.
Georgia Regents Medical Center · USAugusta University · US

Funding

Therapeutic Mechanisms of RhoA Inhibition In Acute Lung InjuryP01HL101902 · NHLBI · AUGUSTA UNIVERSITY · PI BLACK, STEPHEN M · 2011 to 2016
$11.2M
NHLBI NIH HHS HL101902NHLBI NIH HHS P01 HL101902
6 · The paper itself

Abstract

Acute lung injury and acute respiratory distress syndrome are accompanied by thrombin activation and fibrin deposition that enhance lung inflammation, activate endothelial cells and disrupt lung paracellular permeability. Heparin possesses anti-inflammatory properties but its clinical use is limited by hemorrhage and heparin induced thrombocytopenia. We studied the effects of heparin and low anticoagulant 2-O, 3-O desulfated heparin (ODSH) on thrombin-induced increases in paracellular permeability of cultured human pulmonary endothelial cells (ECs). Pretreatment with heparin or ODSH blocked thrombin-induced decrease in the EC transendothelial electrical resistance (TER), attenuated thrombin-stimulated paracellular gap formation and actin cytoskeletal rearrangement. Our data demonstrated that heparin and ODSH had inhibitory effects on thrombin-induced RhoA activation and intracellular calcium elevation. Thrombin-stimulated phosphorylation of the cytoskeletal regulatory proteins, myosin light chain and ezrin/radixin/moesin was also reduced. In these effects, low anticoagulant ODSH was more potent than heparin. Heparin or ODSH alone produced decreases in the EC TER that were abolished by siRNA-mediated depletion of the thrombin receptor, PAR-1. We also demonstrated that, in contrast to heparin, ODSH did not possess thrombin-binding activity. Results suggest that heparin and low anticoagulant ODSH can interfere with thrombin-activated signaling.

Indexed as

ActinsAnticoagulantsCalciumCells, CulturedCytoskeletal ProteinsCytoskeletonEndothelial CellsEndothelium, VascularEzrinHeparinHumansMembrane ProteinsMicrofilament ProteinsMyosin Light ChainsPermeabilityPhosphorylationActinsAnticoagulantsCalciumCytoskeletal ProteinsEzrinHeparinheparin, O-desulfatedMembrane ProteinsMicrofilament ProteinsmoesinMyosin Light ChainsradixinReceptors, ThrombinrhoA GTP-Binding ProteinThrombinEndotheliumHeparinODSHPARThrombin

Identifiers

PMID24469066
PMCPMC4111793
OpenAlexW2019056866

What OpenQuestion holds

Textmetadata
LicenceTDM
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.