ArticleBlood2015
Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 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
22 citing papers in PubMed, 34 citations in OpenAlex.
- Clinical, Molecular, and Bioinformatic Study of Common Thrombophilia Mutation Factor V Leiden.Advances in experimental medicine and biology · 2026Article
- Clinical, Molecular and Bioinformatic Study of Common Thrombophilia Mutation Factor V Leiden.Advances in experimental medicine and biology · 2026Article
- Article
- Article
- Regulation of coagulation by tissue factor pathway inhibitor: Implications for hemophilia therapy.Journal of thrombosis and haemostasis : JTH · 2022Review
- Advocacy of targeting protease-activated receptors in severe coronavirus disease 2019.British journal of pharmacology · 2022Article
- Roles of factor Xa beyond coagulation.Journal of thrombosis and thrombolysis · 2021Article
- Lipid presentation by the protein C receptor links coagulation with autoimmunity.Science (New York, N.Y.) · 2021Article
- Macrophage protease-activated receptor 2 regulates fetal liver erythropoiesis in mice.Blood advances · 2020Article
- Coagulation factor V is a marker of tumor-infiltrating immune cells in breast cancer.Oncoimmunology · 2020Article
- Myeloid cell-synthesized coagulation factor X dampens antitumor immunity.Science immunology · 2019Article
- Activated protein C in neuroprotection and malaria.Current opinion in hematology · 2019Review
- Tissue factor: newer concepts in thrombosis and its role beyond thrombosis and hemostasis.Cardiovascular diagnosis and therapy · 2018Review
- Review
- Article
- Article
- Activated protein C inhibits neutrophil extracellular trap formationThe Journal of biological chemistry · 2017Article
- Individual clotting factor contributions to mortality following trauma.The journal of trauma and acute care surgery · 2017Article
- Occupancy of human EPCR by protein C induces β-arrestin-2 biased PAR1 signaling by both APC and thrombin.Blood · 2016Article
- Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling.Annals of the New York Academy of Sciences · 2016Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
The key effector molecule of the natural protein C pathway, activated protein C (aPC), exerts pleiotropic effects on coagulation, fibrinolysis, and inflammation. Coagulation-independent cell signaling by aPC appears to be the predominant mechanism underlying its highly reproducible therapeutic efficacy in most animal models of injury and infection. In this study, using a mouse model of Staphylococcus aureus sepsis, we demonstrate marked disease stage-specific effects of the anticoagulant and cell signaling functions of aPC. aPC resistance of factor (f)V due to the R506Q Leiden mutation protected against detrimental anticoagulant effects of aPC therapy but also abrogated the anti-inflammatory and mortality-reducing effects of the signaling-selective 5A-aPC variant that has minimal anticoagulant function. We found that procofactor V (cleaved by aPC at R506) and protein S were necessary cofactors for the aPC-mediated inhibition of inflammatory tissue-factor signaling. The anti-inflammatory cofactor function of fV involved the same structural features that govern its cofactor function for the anticoagulant effects of aPC, yet its anti-inflammatory activities did not involve proteolysis of activated coagulation factors Va and VIIIa. These findings reveal a novel biological function and mechanism of the protein C pathway in which protein S and the aPC-cleaved form of fV are cofactors for anti-inflammatory cell signaling by aPC in the context of endotoxemia and infection.
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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.