ArticleJournal of the American Society of Nephrology : JASN2015
Hyperphosphatemia, Phosphoprotein Phosphatases, and Microparticle Release in Vascular Endothelial Cells.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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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
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Impact of Uremic Toxins on Endothelial Dysfunction in Chronic Kidney Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Phosphate binders in chronic kidney disease: a systematic review of recent data.Journal of nephrology · 2016Pooled it
- Review
- Hyperphosphatemia as a potential risk factor for arteriovenous fistula dysfunction: A retrospective study in hemodialysis patients.PloS one · 2025Article
- Renal aging and its consequences: navigating the challenges of an aging population.Frontiers in pharmacology · 2025Review
- Venous Thrombosis in a Pseudohypoparathyroidism Patient with a Novel GNAS Frameshift Mutation and Complete Resolution of Vascular Calcifications with Acetazolamide Treatment.Hormone research in paediatrics · 2024Article
- Similarities and Differences of Vascular Calcification in Diabetes and Chronic Kidney Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Predicting the Cognitive Ability of Young Women Using a New Feature Selection Algorithm.Journal of molecular neuroscience : MN · 2023Article
- Role of transporters in regulating mammalian intracellular inorganic phosphate.Frontiers in pharmacology · 2023Review
- Case report: Sevelamer-associated colitis-a cause of pseudotumor formation with colon perforation and life-threatening bleeding.Frontiers in medicine · 2023Article
- Plasma S-Klotho level affects the risk of hyperuricemia in the middle-aged and elderly people.European journal of medical research · 2022Article
- Microparticles from Hyperphosphatemia-Stimulated Endothelial Cells Promote Vascular Calcification Through Astrocyte-Elevated Gene-1.Calcified tissue international · 2022Article
- RNA-seq analysis of extracellular vesicles from hyperphosphatemia-stimulated endothelial cells provides insight into the mechanism underlying vascular calcification.BMC nephrology · 2022Article
- The Interplay between Uremic Toxins and Albumin, Membrane Transporters and Drug Interaction.Toxins · 2022Review
- Uremic Toxin Lanthionine Induces Endothelial Cell Mineralization In Vitro.Biomedicines · 2022Article
- Phosphate and Endothelial Function: How Sensing of Elevated Inorganic Phosphate Concentration Generates Signals in Endothelial Cells.Advances in experimental medicine and biology · 2022Review
- Extracellular Phosphate, Inflammation and Cytotoxicity.Advances in experimental medicine and biology · 2022Review
- Article
- Vascular Calcification Mechanisms: Updates and Renewed Insight into Signaling Pathways Involved in High Phosphate-Mediated Vascular Smooth Muscle Cell Calcification.Biomedicines · 2021Review
- Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System.Frontiers in physiology · 2021Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperphosphatemia in patients with advanced CKD is thought to be an important contributor to cardiovascular risk, in part because of endothelial cell (EC) dysfunction induced by inorganic phosphate (Pi). Such patients also have an elevated circulating concentration of procoagulant endothelial microparticles (MPs), leading to a prothrombotic state, which may contribute to acute occlusive events. We hypothesized that hyperphosphatemia leads to MP formation from ECs through an elevation of intracellular Pi concentration, which directly inhibits phosphoprotein phosphatases, triggering a global increase in phosphorylation and cytoskeletal changes. In cultured human ECs (EAhy926), incubation with elevated extracellular Pi (2.5 mM) led to a rise in intracellular Pi concentration within 90 minutes. This was mediated by PiT1/slc20a1 Pi transporters and led to global accumulation of tyrosine- and serine/threonine-phosphorylated proteins, a marked increase in cellular Tropomyosin-3, plasma membrane blebbing, and release of 0.1- to 1-μm-diameter MPs. The effect of Pi was independent of oxidative stress or apoptosis. Similarly, global inhibition of phosphoprotein phosphatases with orthovanadate or fluoride yielded a global protein phosphorylation response and rapid release of MPs. The Pi-induced MPs expressed VE-cadherin and superficial phosphatidylserine, and in a thrombin generation assay, they displayed significantly more procoagulant activity than particles derived from cells incubated in medium with a physiologic level of Pi (1 mM). These data show a mechanism of Pi-induced cellular stress and signaling, which may be widely applicable in mammalian cells, and in ECs, it provides a novel pathologic link between hyperphosphatemia, generation of MPs, and thrombotic risk.
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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.