ArticleThrombosis and haemostasis2009
Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1.
Article in Thrombosis and haemostasis, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
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.
Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- Role of Thrombin in Central Nervous System Injury and Disease.Biomolecules · 2021Review
- Thrombin generation and activity in multiple sclerosis.Metabolic brain disease · 2021Review
- Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction.Biomolecules · 2021Article
- Targeting coagulation activation in severe COVID-19 pneumonia: lessons from bacterial pneumonia and sepsis.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- FVIIa (Factor VIIa) Induces Biased Cytoprotective Signaling in Mice Through the Cleavage of PAR (Protease-Activated Receptor)-1 at Canonical Arg41 (Arginine41) Site.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Activated Protein C Attenuates Experimental Autoimmune Encephalomyelitis Progression by Enhancing Vascular Integrity and Suppressing Microglial Activation.Frontiers in neuroscience · 2020Article
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- TR47, a PAR1-based peptide, inhibits melanoma cell migration in vitro and metastasis in vivo.Biochemical and biophysical research communications · 2018Article
- A Novel Compound Targeting Protease Receptor 1 Activators for the Treatment of Glioblastoma.Frontiers in neurology · 2018Article
- G Protein-Coupled Receptor Signaling Through β-Arrestin-Dependent Mechanisms.Journal of cardiovascular pharmacology · 2017Review
- Proximate Mediators of Microvascular Dysfunction at the Blood-Brain Barrier: Neuroinflammatory Pathways to Neurodegeneration.BioMed research international · 2017Review
- Protease-Activated Receptor-1 Supports Locomotor Recovery by Biased Agonist Activated Protein C after Contusive Spinal Cord Injury.PloS one · 2017Article
- Novel pharmaceutical treatments for minimal traumatic brain injury and evaluation of animal models and methodologies supporting their development.Journal of neuroscience methods · 2016Review
- Apolipoprotein E Receptor 2 Mediates Activated Protein C-Induced Endothelial Akt Activation and Endothelial Barrier Stabilization.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- Cyanidin-3-O-Glucoside Ameliorates Lipopolysaccharide-Induced Injury Both In Vivo and In Vitro Suppression of NF-κB and MAPK Pathways.Inflammation · 2015Article
- Thrombin Activity and Thrombin Receptor in Rat Glioblastoma Model: Possible Markers and Targets for Intervention?Journal of molecular neuroscience : MN · 2015Article
- Thrombin regulation of synaptic transmission and plasticity: implications for health and disease.Frontiers in cellular neuroscience · 2015Review
- Factor VIIa binding to endothelial cell protein C receptor protects vascular barrier integrity in vivo.Journal of thrombosis and haemostasis : JTH · 2014Article
- Biased signaling of protease-activated receptors.Frontiers in endocrinology · 2014Review
- Attenuating effect of Ginsenoside Rb1 on LPS-induced lung injury in rats.Journal of inflammation (London, England) · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Protease activated receptor-1 (PAR1) mediates barrier protective signalling of activated protein C (APC) in human endothelial cells in vitro and may contribute to APC's beneficial effects in patients with severe sepsis. Mouse models are of key importance for translational research but species differences may limit conclusions for the human system. We analysed whether mouse APC can cleave, activate and induce signalling through murine PAR1 and tested in newly established mouse models if long-term infusion of APC prevents from vascular leakage. Cell surface immunoassays demonstrated efficient cleavage of endogenous murine endothelial PAR1 by either murine or human APC. Pharmacological concentrations of APC of either species had powerful barrier protective effects on cultured murine endothelial cells that required PAR1 cleavage. Vascular endothelial growth factor-mediated hyperpermeability in the skin was reduced by either endogenously generated as well as directly infused recombinant mouse APC in wild-type mice. However APC did not significantly alter the vascular barrier function in PAR1-deficient mice. In endotoxin-challenged mice, infused APC significantly prevented from pulmonary fluid accumulation in the wild-type mice but not in mice lacking PAR1. Our results directly show that murine APC cleaves and signals through PAR1 in mouse endothelial cells. APC reduces vascular permeability in mouse models and PAR1 plays a major role in mediating these effects. Our data in vitro and in vivo support the paradigm that PAR1 contributes to protective effects of APC on vascular barrier integrity in sepsis.
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Registered trials
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.