ArticleBlood2009
Hyperantithrombotic, noncytoprotective Glu149Ala-activated protein C mutant.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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
48 citing papers in PubMed, 65 citations in OpenAlex.
- Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant.Thrombosis and haemostasis · 2015Trial
- Structural determinants of protease-activated receptor 1 cleavage by activated protein C.Journal of thrombosis and haemostasis : JTH · 2025Article
- Article
- Targeted inhibition of activated protein C by a non-active-site inhibitory antibody to treat hemophilia.Nature communications · 2020Article
- C-terminal residues of activated protein C light chain contribute to its anticoagulant and cytoprotective activities.Journal of thrombosis and haemostasis : JTH · 2020Article
- Neuroprotection and vasculoprotection using genetically targeted protease-ligands.Brain research · 2019Article
- Activated Protein C in Cutaneous Wound Healing: From Bench to Bedside.International journal of molecular sciences · 2019Review
- Review
- Regulation of immune cell signaling by activated protein C.Journal of leukocyte biology · 2018Review
- PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Activated protein C light chain provides an extended binding surface for its anticoagulant cofactor, protein S.Blood advances · 2017Article
- Activated protein C inhibits neutrophil extracellular trap formationThe Journal of biological chemistry · 2017Article
- Cell painting with an engineered EPCR to augment the protein C system.Thrombosis and haemostasis · 2015Article
- Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice.Blood · 2015Article
- Activated protein C: biased for translation.Blood · 2015Review
- WEDGE: an anticoagulant thrombin mutant produced by autoactivation.Journal of thrombosis and haemostasis : JTH · 2015Article
- Article
- Cytoprotective-selective activated protein C therapy for ischaemic stroke.Thrombosis and haemostasis · 2014Review
- Comparative response of platelet fV and plasma fV to activated protein C and relevance to a model of acute traumatic coagulopathy.PloS one · 2014Article
- Neurotoxicity of the anticoagulant-selective E149A-activated protein C variant after focal ischemic stroke in mice.Blood cells, molecules & diseases · 2013Article
Corrections and comments
- Commented on byKnow your APC.2009
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Activated protein C (APC) reduces mortality in severe sepsis patients. APC exerts anticoagulant activities via inactivation of factors Va and VIIIa and cytoprotective activities via endothelial protein C receptor and protease-activated receptor-1. APC mutants with selectively altered and opposite activity profiles, that is, greatly reduced anticoagulant activity or greatly reduced cytoprotective activities, are compared here. Glu149Ala-APC exhibited enhanced in vitro anticoagulant and in vivo antithrombotic activity, but greatly diminished in vitro cytoprotective effects and in vivo reduction of endotoxin-induced murine mortality. Thus, residue Glu149 and the C-terminal region of APC's light chain are identified as functionally important for expression of multiple APC activities. In contrast to Glu149Ala-APC, 5A-APC (Lys191-193Ala + Arg229/230Ala) with protease domain mutations lacked in vivo antithrombotic activity, although it was potent in reducing endotoxin-induced mortality, as previously shown. These data imply that APC molecular species with potent antithrombotic activity, but without robust cytoprotective activity, are not sufficient to reduce mortality in endotoxemia, emphasizing the need for APC's cytoprotective actions, but not anticoagulant actions, to reduce endotoxin-induced mortality. Protein engineering can provide APC mutants that permit definitive mechanism of action studies for APC's multiple activities, and may also provide safer and more effective second-generation APC mutants with reduced bleeding risk.
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.