ArticlePloS one2015
Factor VIII Is Synthesized in Human Endothelial Cells, Packaged in Weibel-Palade Bodies and Secreted Bound to ULVWF Strings.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 83 citations in OpenAlex.
- The effect of F8 missense variants on desmopressin response in people with nonsevere hemophilia A investigated using machine learning.Research and practice in thrombosis and haemostasis · 2026Article
- Factor VIII originates primarily from anatomically distinct subsets of liver sinusoidal endothelial cells.Blood advances · 2026Article
- rFVIIIa-platelet binding enhances platelet procoagulant activity independently of thrombin generation.Blood vessels, thrombosis & hemostasis · 2026Article
- ECMO decannulation is associated with dynamic changes in coagulation profiles: an exploratory, nested cohort study.BMC anesthesiology · 2026Observational
- Retrospective analysis of von willebrand factor and microthrombus formation in septic shock: associations with TTP-like syndrome and sepsis-induced coagulopathy.American journal of clinical and experimental immunology · 2026Article
- Analyzing 6211 unique variants in the upgraded interactive FVIII web database reveals novel insights into hemophilia A.Blood vessels, thrombosis & hemostasis · 2025Article
- Induced Pluripotent (iPSC) and Mesenchymal (MSC) Stem Cells for In Vitro Disease Modeling and Regenerative Medicine.International journal of molecular sciences · 2025Review
- Glioblastoma Cells Express and Secrete Alternatively Spliced Transcripts of Coagulation Factor X.Biomedicines · 2025Article
- Rescue of the endogenous FVIII expression in hemophilia A mice using CRISPR-Cas9 mRNA LNPs.Molecular therapy. Nucleic acids · 2024Article
- Non-viral and viral delivery systems for hemophilia A therapy: recent development and prospects.Annals of hematology · 2024Review
- CD36 regulates factor VIII secretion from liver endothelial cells.Blood advances · 2024Article
- SARS-CoV-2 infection of endothelial cells, dependent on flow-induced ACE2 expression, drives hypercytokinemia in a vascularized microphysiological system.Frontiers in cardiovascular medicine · 2024Article
- CD14+/CD31+ monocytes expanded by UM171 correct hemophilia A in zebrafish upon lentiviral gene transfer of factor VIII.Blood advances · 2023Article
- Influence of rosuvastatin on apolipoproteins and coagulation factor levels: Results from the STAtin Reduce Thrombophilia trial.Research and practice in thrombosis and haemostasis · 2023Article
- Heterogeneity and reciprocity of FVIII and VWF expression, and the response to shear stress in cultured human endothelial cells.Journal of thrombosis and haemostasis : JTH · 2022Article
- Novel Classification of Thrombotic Disorders Based on Molecular Hemostasis and Thrombogenesis Producing Primary and Secondary Phenotypes of Thrombosis.Biomedicines · 2022Review
- Contemporary Biomarkers in Pulmonary Embolism Diagnosis: Moving beyond D-Dimers.Journal of personalized medicine · 2022Review
- Molecular Pathogenesis of Endotheliopathy and Endotheliopathic Syndromes, Leading to Inflammation and Microthrombosis, and Various Hemostatic Clinical Phenotypes Based on "Two-Activation Theory of the Endothelium" and "Two-Path Unifying Theory" of Hemostasis.Medicina (Kaunas, Lithuania) · 2022Review
- Plasma-derived FVIII/VWF complex shows higher protection against inhibitors than isolated FVIII after infusion in haemophilic patients: A translational study.Haemophilia : the official journal of the World Federation of Hemophilia · 2022Article
- The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cellular synthesis site and ensuing storage location for human factor VIII (FVIII), the coagulation protein deficient in hemophilia A, has been elusive. FVIII stability and half-life is dependent on non-covalent complex formation with von Willebrand factor (VWF) to avoid proteolysis and clearance. VWF is synthesized in megakaryocytes and endothelial cells, and is stored and secreted from platelet alpha granules and Weibel-Palade bodies of endothelial cells. In this paper we provide direct evidence for FVIII synthesis in 2 types of primary human endothelial cells: glomerular microvascular endothelial cells (GMVECs) and umbilical vein endothelial cells (HUVECs). Gene expression quantified by real time PCR revealed that levels of F8 and VWF are similar in GMVECs and HUVECs. Previous clinical studies have shown that stimulation of vasopressin V2 receptors causes parallel secretion of both proteins. In this study, we found that both endothelial cell types express AVPR2 (vasopressin V2 receptor gene) and that AVPR2 mRNA levels are 5-fold higher in GMVECs than HUVECs. FVIII and VWF proteins were detected by fluorescent microscopy in Weibel-Palade bodies within GMVECs and HUVECs using antibodies proven to be target specific. Visual presence of FVIII and VWF in Weibel-Palade bodies was confirmed by correlation measurements. The high extent of correlation was compared with negative correlation values obtained from FVIII detection with cytoplasmic proteins, β-actin and Factor H. FVIII activity was positive in GMVEC and HUVEC cell lysates. Stimulated GMVECs and HUVECs were found to secrete cell-anchored ultra-large VWF strings covered with bound FVIII.
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