ArticleBlood2016
What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Absorption, Distribution, Metabolism, and Excretion of US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.Drug metabolism and disposition: the biological fate of chemicals · 2022Pooled it
- A phase 2 trial of defibrotide for the prevention of chimeric antigen receptor T-cell-associated neurotoxicity syndrome.Blood advances · 2023Trial
- Trial
- Defibrotide Therapy for SARS-CoV-2 ARDS.Chest · 2022Trial
- Acute Graft-vs.-Host Disease-Associated Endothelial ActivationFrontiers in immunology · 2019Trial
- Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome.British journal of haematology · 2018Trial
- Associations between levels of insulin-like growth factor 1 and sinusoidal obstruction syndrome after allogeneic haematopoietic stem cell transplantation.Bone marrow transplantation · 2017Trial
- Evaluation of Prophylactic Defibrotide Use in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Multicenter Retrospective Cohort Study.Journal of personalized medicine · 2026Article
- Post-Thrombotic Syndrome: Pathophysiology, Clinical Implications, and Advances in Management.Health science reports · 2025Article
- Evaluating the safety profile of defibrotide in sickle cell disease: anHaematologica · 2025Article
- Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19.Biomolecules · 2025Review
- Targeting Intestinal Permeability for Graft-versus-Host Disease Treatment: A Therapeutic Perspective with Defibrotide.Journal of experimental pharmacology · 2025Article
- Article
- Mafosfamide, a cyclophosphamide analog, causes a proinflammatory response and increased permeability on endothelial cells in vitro.Bone marrow transplantation · 2023Article
- Rare variants in complement system genes associate with endothelial damage after pediatric allogeneic hematopoietic stem cell transplantation.Frontiers in immunology · 2023Article
- Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications?Cardiovascular drugs and therapy · 2022Review
- An endothelial proinflammatory phenotype precedes the development of the engraftment syndrome after autologous Hct.Bone marrow transplantation · 2022Article
- The importance of endothelial protection: the emerging role of defibrotide in reversing endothelial injury and its sequelae.Bone marrow transplantation · 2021Review
- Endothelium-protective, histone-neutralizing properties of the polyanionic agent defibrotide.JCI insight · 2021Article
- COVID-19-induced endotheliitis: emerging evidence and possible therapeutic strategies.British journal of haematology · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defibrotide (DF) has received European Medicines Agency authorization to treat sinusoidal obstruction syndrome, an early complication after hematopoietic cell transplantation. DF has a recognized role as an endothelial protective agent, although its precise mechanism of action remains to be elucidated. The aim of the present study was to investigate the interaction of DF with endothelial cells (ECs). A human hepatic EC line was exposed to different DF concentrations, previously labeled. Using inhibitory assays and flow cytometry techniques along with confocal microscopy, we explored: DF-EC interaction, endocytic pathways, and internalization kinetics. Moreover, we evaluated the potential role of adenosine receptors in DF-EC interaction and if DF effects on endothelium were dependent of its internalization. Confocal microscopy showed interaction of DF with EC membranes followed by internalization, though DF did not reach the cell nucleus even after 24 hours. Flow cytometry revealed concentration, temperature, and time dependent uptake of DF in 2 EC models but not in other cell types. Moreover, inhibitory assays indicated that entrance of DF into ECs occurs primarily through macropinocytosis. Our experimental approach did not show any evidence of the involvement of adenosine receptors in DF-EC interaction. The antiinflammatory and antioxidant properties of DF seem to be caused by the interaction of the drug with the cell membrane. Our findings contribute to a better understanding of the precise mechanisms of action of DF as a therapeutic and potential preventive agent on the endothelial damage underlying different pathologic situations.
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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.