ArticleBlood2021
Factor VIIa induces extracellular vesicles from the endothelium: a potential mechanism for its hemostatic effect.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 40 citations in OpenAlex.
- Lipid Cargo of Small Extracellular Vesicles as a Novel Contributor to Cardiovascular Diseases.International journal of molecular sciences · 2026Review
- Thrombin concentration shapes endothelial extracellular vesicle profiles with divergent inflammatory functions.Blood advances · 2026Article
- Extracellular Vesicles in Cardiac Cell Crosstalk: from Intercellular Communication to Clinical Translation.Cardiovascular drugs and therapy · 2026Review
- Potential Mechanisms of Platelet Dysfunction and Bleeding in Acid Sphingomyelinase Deficiency.Cells · 2026Review
- The effects of recombinant human activated factor VII and tranexamic acid on traumatic bleeding and mortality in mice.Research and practice in thrombosis and haemostasis · 2026Article
- Extracellular Vesicles Contribute to the Pathophysiology and Progression of Pleural Fibrosis by Promoting Mesothelial-to-Mesenchymal Transition and Neoangiogenesis.American journal of respiratory cell and molecular biology · 2025Article
- MicroRNAs in lung cancer: their role in tumor progression, biomarkers, diagnostic, prognostic, and therapeutic relevance.Discover oncology · 2025Review
- Recombinant factor VIIa: new insights into the mechanism of action through product innovation.Research and practice in thrombosis and haemostasis · 2025Review
- Coagulation protease-induced extracellular vesicles: their potential effects on coagulation and inflammation.Journal of thrombosis and haemostasis : JTH · 2024Review
- Extracellular Vesicles as Mediators in Atherosclerotic Cardiovascular Disease.Journal of lipid and atherosclerosis · 2024Review
- Coagulation Protease-Driven Cancer Immune Evasion: Potential Targets for Cancer Immunotherapy.Cancers · 2024Review
- Article
- MicroRNA-10a enrichment in factor VIIa-released endothelial extracellular vesicles: potential mechanisms.Journal of thrombosis and haemostasis : JTH · 2024Article
- The role of extracellular vesicles in the pathogenesis of gynecological cancer.Frontiers in oncology · 2024Review
- Factor VIIa releases phosphatidylserine-enriched extracellular vesicles from endothelial cells by activating acid sphingomyelinase.Journal of thrombosis and haemostasis : JTH · 2023Article
- Lyophilized apoptotic vesicle-encapsulated adhesive hydrogel sponge as a rapid hemostat for traumatic hemorrhage in coagulopathy.Journal of nanobiotechnology · 2023Article
- Extracellular Vesicles in Triple-Negative Breast Cancer: Immune Regulation, Biomarkers, and Immunotherapeutic Potential.Cancers · 2023Review
- Review
- The Role of Extracellular Vesicles in the Pathogenesis of Hematological Malignancies: Interaction with Tumor Microenvironment; a Potential Biomarker and Targeted Therapy.Biomolecules · 2023Review
- The Magic of Proteases: From a Procoagulant and Anticoagulant Factor V to an Equitable Treatment of Its Inherited Deficiency.International journal of molecular sciences · 2023Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Recombinant factor FVIIa (rFVIIa) is used as a hemostatic agent to treat bleeding disorders in hemophilia patients with inhibitors and other groups of patients. Our recent studies showed that FVIIa binds endothelial cell protein C receptor (EPCR) and induces protease-activated receptor 1 (PAR1)-mediated biased signaling. The importance of FVIIa-EPCR-PAR1-mediated signaling in hemostasis is unknown. In the present study, we show that FVIIa induces the release of extracellular vesicles (EVs) from endothelial cells both in vitro and in vivo. Silencing of EPCR or PAR1 in endothelial cells blocked the FVIIa-induced generation of EVs. Consistent with these data, FVIIa treatment enhanced the release of EVs from murine brain endothelial cells isolated from wild-type (WT), EPCR-overexpressing, and PAR1-R46Q-mutant mice, but not EPCR-deficient or PAR1-R41Q-mutant mice. In vivo studies revealed that administration of FVIIa to WT, EPCR-overexpressing, and PAR1-R46Q-mutant mice, but not EPCR-deficient or PAR1-R41Q-mutant mice, increased the number of circulating EVs. EVs released in response to FVIIa treatment exhibit enhanced procoagulant activity. Infusion of FVIIa-generated EVs and not control EVs to platelet-depleted mice increased thrombin generation at the site of injury and reduced blood loss. Administration of FVIIa-generated EVs or generation of EVs endogenously by administering FVIIa augmented the hemostatic effect of FVIIa. Overall, our data reveal that FVIIa treatment, through FVIIa-EPCR-PAR1 signaling, releases EVs from the endothelium into the circulation, and these EVs contribute to the hemostatic effect of FVIIa.
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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.