ArticleBlood2006
Roles of protease-activated receptors in a mouse model of endotoxemia.
Article in Blood, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 102 citations in OpenAlex.
- A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome.BMC pulmonary medicine · 2012Trial
- Proteinase-Activated Receptor 2 (PAR2) Deficiency and Cardiovascular Regulation: Context-Dependent Effects on Inflammation and Fibrosis.Current issues in molecular biology · 2026Review
- Intercellular synergy between protease-activated receptors 1 and 4 during mouse development.Journal of thrombosis and haemostasis : JTH · 2025Article
- Acetaminophen Overdose Reveals PAR4 as a Low-Expressing but Potent Receptor on the Hepatic Endothelium in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Endothelial protease-activated receptor 4: impotent or important?Frontiers in cardiovascular medicine · 2025Review
- 1-Piperidine Propionic Acid Protects from Septic Shock Through Protease Receptor 2 Inhibition.International journal of molecular sciences · 2024Article
- Recombinant ADAMTS-13 Improves Survival of Mice Subjected to Endotoxemia.International journal of molecular sciences · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Relative platelet reductions provide better pathophysiologic signatures of coagulopathies in sepsis.Scientific reports · 2021Article
- 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
- The Multifaceted Function of Granzymes in Sepsis: Some Facts and a Lot to Discover.Frontiers in immunology · 2020Review
- Roles of Coagulation Proteases and PARs (Protease-Activated Receptors) in Mouse Models of Inflammatory Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Platelets in Sepsis: An Update on Experimental Models and Clinical Data.Frontiers in immunology · 2019Review
- SCH79797 improves outcomes in experimental bacterial pneumonia by boosting neutrophil killing and direct antibiotic activity.The Journal of antimicrobial chemotherapy · 2018Article
- The podoplanin-CLEC-2 axis inhibits inflammation in sepsis.Nature communications · 2017Article
- Platelet and Erythrocyte Sources of S1P Are Redundant for Vascular Development and Homeostasis, but Both Rendered Essential After Plasma S1P Depletion in Anaphylactic Shock.Circulation research · 2016Article
- Membrane lipid peroxidation in neurodegeneration: Role of thrombin and proteinase-activated receptor-1.Brain research · 2016Article
- New paradigms in sepsis: from prevention to protection of failing microcirculation.Journal of thrombosis and haemostasis : JTH · 2015Review
- Suppression of peripheral sympathetic activity underlies protease-activated receptor 2-mediated hypotension.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2014Article
- Differential signaling by protease-activated receptors: implications for therapeutic targeting.International journal of molecular sciences · 2014Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Endotoxemia is often associated with extreme inflammatory responses and disseminated intravascular coagulation. Protease-activated receptors (PARs) mediate cellular responses to coagulation proteases, including platelet activation and endothelial cell reactions predicted to promote inflammation. These observations suggested that PAR activation by coagulation proteases generated in the setting of endotoxemia might promote platelet activation, leukocyte-mediated endothelial injury, tissue damage, and death. Toward testing these hypotheses, we examined the effect of PAR deficiencies that ablate platelet and endothelial activation by coagulation proteases in a mouse endotoxemia model. Although coagulation was activated as measured by thrombin-antithrombin (TAT) production and antithrombin III (ATIII) depletion, Par1(-/-), Par2(-/-), Par4(-/-), Par2(-/-):Par4(-/-), and Par1(-/-):Par2(-/-) mice all failed to show improved survival or decreased cytokine responses after endotoxin challenge compared with wild type. Thus, our results fail to support a necessary role for PARs in linking coagulation to inflammation or death in this model. Interestingly, endotoxin-induced thrombocytopenia was not diminished in Par4(-/-) mice. Thus, a mechanism independent of platelet activation by thrombin was sufficient to cause thrombocytopenia in our model. These results raise the possibility that decreases in platelet count in the setting of sepsis may not be caused by disseminated intravascular coagulation but instead report on a sometimes parallel but independent process.
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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.