ArticleBlood2018
Factor VIIa induces anti-inflammatory signaling via EPCR and PAR1.
Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- A Beginner's Guide to Study the Role of Extracellular Vesicles in Coagulation.Journal of extracellular biology · 2026Review
- Review
- Liver specific-inhibition of LPCAT3 ameliorates metabolic dysfunction-associated steatotic liver disease.Journal of molecular medicine (Berlin, Germany) · 2026Article
- LPCAT3-dependent remodeling of the phospholipids and lipid rafts is essential for vascular proinflammatory signaling and the development of atherosclerosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Double-negative T cells in combination with ursodeoxycholic acid ameliorates immune-mediated cholangitis in mice.BMC medicine · 2025Article
- Endothelial Protein C Receptor: A Multifunctional Mediator in the Pathophysiology of Rheumatoid Arthritis.Cells · 2025Review
- Thrombomodulin: A key regulator of intravascular blood coagulation, fibrinolysis, and inflammation, and a treatment for disseminated intravascular coagulation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- Protease-activated receptors in vascular smooth muscle cells: a bridge between thrombo-inflammation and vascular remodelling.Cell communication and signaling : CCS · 2025Review
- Multi-omics Analysis to Identify Key Immune Genes for Osteoporosis based on Machine Learning and Single-cell Analysis.Orthopaedic surgery · 2024Article
- Coagulation protease-induced extracellular vesicles: their potential effects on coagulation and inflammation.Journal of thrombosis and haemostasis : JTH · 2024Review
- Endothelial Protein C Receptor and Its Impact on Rheumatic Disease.Journal of clinical medicine · 2024Review
- Inhibition of the MALT1-LPCAT3 axis protects cartilage degeneration and osteoarthritis.Cell communication and signaling : CCS · 2024Article
- Thrombomodulin Switches Signaling and Protease-Activated Receptor 1 Cleavage Specificity of Thrombin.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- MicroRNA-10a enrichment in factor VIIa-released endothelial extracellular vesicles: potential mechanisms.Journal of thrombosis and haemostasis : JTH · 2024Article
- Factor VIIa releases phosphatidylserine-enriched extracellular vesicles from endothelial cells by activating acid sphingomyelinase.Journal of thrombosis and haemostasis : JTH · 2023Article
- Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s.mSphere · 2023Article
- The pathogenesis of obstetric APS: a 2023 update.Clinical immunology (Orlando, Fla.) · 2023Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages.Journal of nanobiotechnology · 2022Article
- Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.Nature communications · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies show that endothelial cell protein C receptor (EPCR) interacts with diverse ligands, in addition to its known ligands protein C and activated protein C (APC). We showed in earlier studies that procoagulant clotting factor VIIa (FVIIa) binds EPCR and downregulates EPCR-mediated anticoagulation and induces an endothelial barrier protective effect. Here, we investigated the effect of FVIIa's interaction with EPCR on endothelial cell inflammation and lipopolysaccharide (LPS)-induced inflammatory responses in vivo. Treatment of endothelial cells with FVIIa suppressed tumor necrosis factor α (TNF-α)- and LPS-induced expression of cellular adhesion molecules and adherence of monocytes to endothelial cells. Inhibition of EPCR or protease-activated receptor 1 (PAR1) by either specific antibodies or small interfering RNA abolished the FVIIa-induced suppression of TNF-α- and LPS-induced expression of cellular adhesion molecules and interleukin-6. β-Arrestin-1 silencing blocked the FVIIa-induced anti-inflammatory effect in endothelial cells. In vivo studies showed that FVIIa treatment markedly suppressed LPS-induced inflammatory cytokines and infiltration of innate immune cells into the lung in wild-type and EPCR-overexpressing mice, but not in EPCR-deficient mice. Mechanistic studies revealed that FVIIa treatment inhibited TNF-α-induced ERK1/2, p38 MAPK, JNK, NF-κB, and C-Jun activation indicating that FVIIa-mediated signaling blocks an upstream signaling event in TNFα-induced signaling cascade. FVIIa treatment impaired the recruitment of TNF-receptor-associated factor 2 into the TNF receptor 1 signaling complex. Overall, our present data provide convincing evidence that FVIIa binding to EPCR elicits anti-inflammatory signaling via a PAR1- and β-arrestin-1 dependent pathway. The present study suggests new therapeutic potentials for FVIIa, which is currently in clinical use for treating bleeding disorders.
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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.