ArticleJournal of thrombosis and haemostasis : JTH2020
Modulation of endothelial organelle size as an antithrombotic strategy.
Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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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
12 citing papers in PubMed, 19 citations in OpenAlex.
- O-glycan determinants regulate VWF trafficking to Weibel-Palade bodies.Blood advances · 2024Article
- COVID-19 increases extracorporeal coagulation during hemodialysis associated with upregulation of vWF/FBLN5 signaling in patients with severe/critical symptoms.BMC infectious diseases · 2024Article
- Clusterin knockdown has effects on intracellular and secreted von Willebrand factor in human umbilical vein endothelial cells.PloS one · 2024Article
- Altered Storage and Function of von Willebrand Factor in Human Cardiac Microvascular Endothelial Cells Isolated from Recipient Transplant Hearts.International journal of molecular sciences · 2023Article
- Automated segmentation and quantitative analysis of organelle morphology, localization and content using CellProfiler.PloS one · 2023Article
- Dispatch and delivery at the ER-Golgi interface: how endothelial cells tune their hemostatic response.The FEBS journal · 2022Article
- Structure modeling hints at a granular organization of the Golgi ribbon.BMC biology · 2022Article
- Shrinking Weibel-Palade bodies prevents high platelet recruitment in assays using thrombotic thrombocytopenic purpura plasma.Research and practice in thrombosis and haemostasis · 2021Article
- The Intriguing Relationships of von Willebrand Factor, ADAMTS13 and Cardiac Disease.Journal of cardiovascular development and disease · 2021Review
- Weibel Palade Bodies: Unique Secretory Organelles of Endothelial Cells that Control Blood Vessel Homeostasis.Frontiers in cell and developmental biology · 2021Review
- Inactivation of Cerebral Cavernous Malformation Genes Results in Accumulation of von Willebrand Factor and Redistribution of Weibel-Palade Bodies in Endothelial Cells.Frontiers in molecular biosciences · 2021Article
- Modulation of endothelial organelle size as an antithrombotic strategy.Journal of thrombosis and haemostasis : JTH · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIt is long established that von Willebrand factor (VWF) is central to hemostasis and thrombosis. Endothelial VWF is stored in cell-specific secretory granules, Weibel-Palade bodies (WPBs), organelles generated in a wide range of lengths (0.5-5.0 µm). WPB size responds to physiological cues and pharmacological treatment, and VWF secretion from shortened WPBs dramatically reduces platelet and plasma VWF adhesion to an endothelial surface.
objectiveWe hypothesized that WPB-shortening represented a novel target for antithrombotic therapy. Our objective was to determine whether compounds exhibiting this activity do exist.
methodsUsing a microscopy approach coupled to automated image analysis, we measured the size of WPB bodies in primary human endothelial cells treated with licensed compounds for 24 hours. RESULTS AND
conclusionsA novel approach to identification of antithrombotic compounds generated a significant number of candidates with the ability to shorten WPBs. In vitro assays of two selected compounds confirm that they inhibit the pro-hemostatic activity of secreted VWF. This set of compounds acting at a very early stage of the hemostatic process could well prove to be a useful adjunct to current antithrombotic therapeutics. Further, in the current SARS-CoV-2 pandemic, with a considerable fraction of critically ill COVID-19 patients affected by hypercoagulability, these WPB size-reducing drugs might also provide welcome therapeutic leads for frontline clinicians and researchers.
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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 Socratic graph.