ArticleJournal of cellular and molecular medicine2017
Extracellular histones disarrange vasoactive mediators release through a COX-NOS interaction in human endothelial cells.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Role of post-translational modifications in modulating histone reactivity in the extracellular environment.Biochemical Society transactions · 2026Review
- Circulating histones as clinical biomarkers in critically ill conditions.FEBS letters · 2025Review
- Human Brain Endothelial Cell-Derived Extracellular Vesicles ReduceInternational journal of molecular sciences · 2025Article
- Review
- Validation of circulating histone detection by mass spectrometry for early diagnosis, prognosis, and management of critically ill septic patients.Journal of translational medicine · 2023Article
- Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells.Journal of physiology and biochemistry · 2023Article
- Histone Citrullination Mediates a Protective Role in Endothelium and Modulates Inflammation.Cells · 2022Article
- Endothelial Cells Activated by Extracellular Histones Promote Foxp3International journal of molecular sciences · 2022Article
- HJournal of nanobiotechnology · 2022Article
- Extracellular Histones Activate Endothelial NLRP3 Inflammasome and are Associated with a Severe Sepsis Phenotype.Journal of inflammation research · 2022Article
- Comparative Analysis of Chromatin-Delivered Biomarkers in the Monitoring of Sepsis and Septic Shock: A Pilot Study.International journal of molecular sciences · 2021Article
- Recent advances in Extracellular Vesicles and their involvements in vasculitis.Free radical biology & medicine · 2021Review
- Circulating Histones in Sepsis: Potential Outcome Predictors and Therapeutic Targets.Frontiers in immunology · 2021Review
- Extract fromACS omega · 2020Article
- Exosomes from adipose tissue-derived mesenchymal stem cells ameliorate histone-induced acute lung injury by activating the PI3K/Akt pathway in endothelial cells.Stem cell research & therapy · 2020Article
- Cystathionine β-synthase and methylenetetrahydrofolate reductase mutations in Mexican individuals with hyperhomocysteinemia.SAGE open medicine · 2020Article
- Heparin Attenuates Histone-Mediated Cytotoxicity in Septic Acute Kidney Injury.Frontiers in medicine · 2020Article
- The Role of Neutrophils and Neutrophil Extracellular Traps in Vascular Damage in Systemic Lupus Erythematosus.Journal of clinical medicine · 2019Review
- Extracellular vesicles in autoimmune vasculitis - Little dirts light the fire in blood vessels.Autoimmunity reviews · 2019Review
- Flavin Oxidase-Induced ROS Generation Modulates PKC Biphasic Effect of Resveratrol on Endothelial Cell Survival.Biomolecules · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone-mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose-dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) mRNA and protein expression, decreased COX-1 mRNA levels and did not change thromboxane A2 synthase (TXAS) expression. Moreover, extracellular histones decreased both, eNOS expression and NO production in HUVEC. The impaired NO production was related to COX-2 activity and superoxide production since was reversed after celecoxib (10 μmol/l) and tempol (100 μmol/l) treatments, respectively. In conclusion, our findings suggest that extracellular histones stimulate the release of endothelial-dependent mediators through an up-regulation in COX-2-PGIS-PGI2 pathway which involves a COX-2-dependent superoxide production that decreases the activity of eNOS and the NO production. These effects may contribute to the endothelial cell dysfunction observed in histone-mediated pathologies.
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Registered trials
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