ArticlePloS one2016
Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- N-myc and STAT interactor promotes poly(I:C)-induced pulmonary coagulopathy via STAT3-dependent tissue factor.Frontiers in immunology · 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
- Unraveling NETs in Sepsis: From Cellular Mechanisms to Clinical Relevance.International journal of molecular sciences · 2025Review
- Disseminated intravascular coagulation.Journal of intensive care · 2025Review
- Interplay of genetic and clinical factors in cancer-associated thrombosis: Deciphering the prothrombotic landscape of colorectal cancer.World journal of gastroenterology · 2025Review
- Unraveling the deadly dance: endothelial cells and neutrophils in sepsis-induced acute lung injury/acute respiratory distress syndrome.Frontiers in cell and developmental biology · 2025Review
- Neutrophils Extracellular Traps Impair Lung Endothelial Proliferation in Sepsis via PLK1 Inhibition and Cell Cycle Arrest.Journal of inflammation research · 2025Article
- Extracellular histones: a unifying mechanism driving platelet-dependent extracellular vesicle release and thrombus formation in COVID-19.Journal of thrombosis and haemostasis : JTH · 2024Article
- Pathophysiology of Disseminated Intravascular Coagulation in Sepsis: A Clinically Focused Overview.Cells · 2023Review
- The Polyanionic Drug Suramin Neutralizes Histones and Prevents Endotheliopathy.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Validation of circulating histone detection by mass spectrometry for early diagnosis, prognosis, and management of critically ill septic patients.Journal of translational medicine · 2023Article
- The role of extracellular histones in COVID-19.Journal of internal medicine · 2023Review
- Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses.Critical care (London, England) · 2023Review
- Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation.Research and practice in thrombosis and haemostasis · 2023Article
- Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis.Clinical and translational medicine · 2023Review
- Neutrophil Extracellular Traps in Cerebral Ischemia/Reperfusion Injury: Friend and Foe.Current neuropharmacology · 2023Review
- Extracellular Histones Trigger Disseminated Intravascular Coagulation by Lytic Cell Death.International journal of molecular sciences · 2022Article
- Nets, pulmonary arterial hypertension, and thrombo-inflammation.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Endothelial Cells Activated by Extracellular Histones Promote Foxp3International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.
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