ArticleBlood2024
Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Safety of factor XI inhibitors compared to factor X inhibitors in atrial fibrillation: a systematic review and meta-analysis.Journal of thrombosis and thrombolysis · 2025Pooled it
- Factor XI(a) Inhibition in Secondary Stroke Prevention: On the Cusp of a New Anticoagulation Paradigm.ACS pharmacology & translational science · 2026Article
- The OCEANIC trial journey: from failure to breakthrough?European heart journal. Cardiovascular pharmacotherapy · 2026Article
- Factor XI Inhibition for Ischemic Stroke Secondary Prevention: Pharmacology, Clinical Evidence, and Future Directions.Journal of clinical pharmacology · 2026Review
- SERPINE1 in ARDS: an emerging regulator of inflammation-coagulation-fibrinolysis crosstalk.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Compact and informative representation learning for scRNA-seq data clustering with masked information bottleneck.BMC biology · 2026Article
- Plasma proteomics reveals the molecular features in rapidly progressive pneumoconiosis.Frontiers in immunology · 2026Article
- Paeonol Inhibits the MAPK Signaling Pathway by Targeting SIRT1 in AGE-Induced HUVECs Injury.Combinatorial chemistry & high throughput screening · 2026Article
- An Ang-1-releasing self-assembling peptide coating for inflammation modulation and suppression of smooth muscle proliferation.Frontiers in bioengineering and biotechnology · 2026Article
- Endothelial barrier and sepsis: mechanisms and potential therapeutic strategies.Military Medical Research · 2026Review
- Case Report: Upper extremity deep vein thrombosis revealing an occult invasive ductal breast carcinoma.Frontiers in cardiovascular medicine · 2026Article
- Insights from the Evolution of Coagulation: A New Perspective on Anti-Inflammatory Strategies in the ICU-Focus on the Contact Activation System.Biomedicines · 2025Review
- Factor XI inhibitors for the prevention and treatment of venous and arterial thromboembolism.Nature reviews. Cardiology · 2025Review
- Bacterial infection and activation of the contact pathway of coagulation.Blood vessels, thrombosis & hemostasis · 2025Review
- Protective effects of factor XI inhibition by abelacimab in a baboon model of live Staphylococcus aureus sepsis.Journal of thrombosis and haemostasis : JTH · 2025Article
- Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism.Blood · 2025Observational
- Factor XI and Cancer: Physiopathological Linkage and Clinical Perspectives.Journal of clinical medicine · 2025Review
- Artificial Intelligence-Driven Proteomics Identifies Plasma Protein Signatures for Diagnosis and Stratification of Behçet's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Biological attributes of zinc-dependent endopeptidases in endothelial dysfunction associated with sepsis: a narrative review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
abstractLoss of endothelial barrier function contributes to the pathophysiology of many inflammatory diseases. Coagulation factor XI (FXI) plays a regulatory role in inflammation. Although activation of FXI increases vascular permeability in vivo, the mechanism by which FXI or its activated form FXIa disrupts endothelial barrier function is unknown. We investigated the role of FXIa in human umbilical vein endothelial cell (HUVEC) or human aortic endothelial cell (HAEC) permeability. The expression patterns of vascular endothelial (VE)-cadherin and other proteins of interest were examined by western blot or immunofluorescence. Endothelial cell permeability was analyzed by Transwell assay. We demonstrate that FXIa increases endothelial cell permeability by inducing cleavage of the VE-cadherin extracellular domain, releasing a soluble fragment. The activation of a disintegrin and metalloproteinase 10 (ADAM10) mediates the FXIa-dependent cleavage of VE-cadherin, because adding an ADAM10 inhibitor prevented the cleavage of VE-cadherin induced by FXIa. The binding of FXIa with plasminogen activator inhibitor 1 and very low-density lipoprotein receptor on HUVEC or HAEC surfaces activates vascular endothelial growth receptor factor 2 (VEGFR2). The activation of VEGFR2 triggers the mitogen-activated protein kinase (MAPK) signaling pathway and promotes the expression of active ADAM10 on the cell surface. In a pilot experiment using an established baboon model of sepsis, the inhibition of FXI activation significantly decreased the levels of soluble VE-cadherin to preserve barrier function. This study reveals a novel pathway by which FXIa regulates vascular permeability. The effect of FXIa on barrier function may be another way by which FXIa contributes to the development of inflammatory diseases.
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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.