ArticleAmerican journal of respiratory cell and molecular biology2011
Cytoprotective-selective activated protein C attenuates Pseudomonas aeruginosa-induced lung injury in mice.
Article in American journal of respiratory cell and molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
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
24 citing papers in PubMed, 36 citations in OpenAlex.
- Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial.PloS one · 2014Trial
- Lung endothelium, tau, and amyloids in health and disease.Physiological reviews · 2024Review
- Activated Protein C Protects against Murine Contact Dermatitis by Suppressing Protease-Activated Receptor 2.International journal of molecular sciences · 2022Article
- COVID-19 hypothesis: Activated protein C for therapy of virus-induced pathologic thromboinflammation.Research and practice in thrombosis and haemostasis · 2020Article
- Neuronal Wiskott-Aldrich syndrome protein regulates Pseudomonas aeruginosa-induced lung vascular permeability through the modulation of actin cytoskeletal dynamics.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Activated Protein C in Cutaneous Wound Healing: From Bench to Bedside.International journal of molecular sciences · 2019Review
- An ADAM-10 dependent EPCR shedding links meningococcal interaction with endothelial cells to purpura fulminans.PLoS pathogens · 2018Article
- New insights into the mechanisms of pulmonary edema in acute lung injury.Annals of translational medicine · 2018Review
- Apolipoprotein E Receptor 2 Mediates Activated Protein C-Induced Endothelial Akt Activation and Endothelial Barrier Stabilization.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- Activated protein C: biased for translation.Blood · 2015Review
- Hyaluronan mediates airway hyperresponsiveness in oxidative lung injury.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Thrombomodulin/activated protein C system in septic disseminated intravascular coagulation.Journal of intensive care · 2015Article
- Variable importance and prediction methods for longitudinal problems with missing variables.PloS one · 2015Article
- Cytoprotective-selective activated protein C therapy for ischaemic stroke.Thrombosis and haemostasis · 2014Review
- Postexposure aerosolized heparin reduces lung injury in chlorine-exposed mice.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Mechanisms of phagocytosis and host clearance of Pseudomonas aeruginosa.American journal of physiology. Lung cellular and molecular physiology · 2014Review
- Neurotoxicity of the anticoagulant-selective E149A-activated protein C variant after focal ischemic stroke in mice.Blood cells, molecules & diseases · 2013Article
- Mechanisms of anticoagulant and cytoprotective actions of the protein C pathway.Journal of thrombosis and haemostasis : JTH · 2013Review
- HMGB1 accelerates alveolar epithelial repair via an IL-1β- and αvβ6 integrin-dependent activation of TGF-β1.PloS one · 2013Article
- Cecal ligation and puncture-induced murine sepsis does not cause lung injury.Critical care medicine · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Inhibition of the small GTPase RhoA attenuates the development of pulmonary edema and restores positive alveolar fluid clearance in a murine model of Pseudomonas aeruginosa pneumonia. Activated protein C (aPC) blocks the development of an unfavorably low ratio of small GTPase Rac1/RhoA activity in lung endothelium through endothelial protein C receptor (EPCR)/protease-activated receptor-1 (PAR-1)-dependent signaling mechanisms that include transactivating the sphingosine-1-phosphate (S1P) pathway. However, whether aPC's cytoprotective effects can attenuate the development of pulmonary edema and death associated with P. aeruginosa pneumonia in mice remains unknown. Thus, we determined whether the normalization of a depressed ratio of activated Rac1/RhoA by aPC would attenuate the P. aeruginosa-mediated increase in protein permeability across lung endothelial and alveolar epithelial barriers. Pretreatment with aPC significantly reduced P. aeruginosa-induced increases in paracellular permeability across pulmonary endothelial cell and alveolar epithelial monolayers via an inhibition of RhoA activation and a promotion of Rac1 activation that required the EPCR-PAR-1 and S1P pathways. Furthermore, pretreatment with aPC attenuated the development of pulmonary edema in a murine model of P. aeruginosa pneumonia. Finally, a cytoprotective-selective aPC mutant, aPC-5A, which lacks most of aPC's anticoagulant activity, reproduced the protective effect of wild-type aPC by attenuating the development of pulmonary edema and decreasing mortality in a murine model of P. aeruginosa pneumonia. Taken together, these results demonstrate a critical role for the cytoprotective activities of aPC in attenuating P. aeruginosa-induced lung vascular permeability and mortality, suggesting that cytoprotective-selective aPC-5A with diminished bleeding risks could attenuate the lung damage caused by P. aeruginosa in critically ill patients.
Indexed as
Identifiers
What OpenQuestion holds
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.