ArticleBiochemical and biophysical research communications2011
Nitric oxide counters the inhibitory effects of uremic toxin indoxyl sulfate on endothelial cells by governing ERK MAP kinase and myosin light chain activation.
Article in Biochemical and biophysical research communications, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- The Role of Diet and Gut Microbiome in CKD Progression and Therapy.Journal of clinical medicine · 2026Review
- The microbial metabolite p-cresol compromises the vascular barrier and induces endothelial cytotoxicity and inflammation in a 3D human vessel-on-a-chip.Scientific reports · 2024Article
- The Role of Palmitic Acid in the Co-Toxicity of Bacterial Metabolites to Endothelial Cells.Vascular health and risk management · 2023Article
- Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex.Antioxidants (Basel, Switzerland) · 2021Article
- Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2021Article
- Review
- Developmental Programming and Reprogramming of Hypertension and Kidney Disease: Impact of Tryptophan Metabolism.International journal of molecular sciences · 2020Review
- Uremic Toxins and Vascular Dysfunction.Toxins · 2020Review
- Indoxyl Sulfate, a Uremic Endotheliotoxin.Toxins · 2020Review
- Indoxyl Sulfate Stimulates Angiogenesis by Regulating Reactive Oxygen Species Production via CYP1B1.Toxins · 2019Article
- Prognostic Utility of Indoxyl Sulfate for Patients with Acute Coronary Syndrome.Journal of atherosclerosis and thrombosis · 2019Article
- Review
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Uremic toxins such as indoxyl sulfate (IS) accumulate at a high level in end stage renal disease (ESRD) and can exhibit significant systemic endothelial toxicity leading to accelerated cardiovascular events. The precise molecular mechanisms by which IS causes endothelial dysfunction are unknown. We tested the hypothesis that IS negatively influences properties of endothelial cells, such as migration and tube formation, by depleting nitric oxide (NO) bioavailability, and that an NO donor can reverse these inhibitory effects. IS inhibited human umbilical vein endothelial cell (HUVEC) migration and formation of tubes on matrigel. Mechanistically, IS inhibited VEGF-induced NO release from HUVECs. An NO donor, SNAP, reversed IS-mediated inhibition of HUVEC migration as well as tube-formation. IS inhibited ERK 1/2 MAP kinase activity in a dose-dependent manner, but this was preserved by SNAP. Inhibition of ERK 1/2 with a pharmacological inhibitor (U0126) decreased HUVEC migration and tube formation; these effects too were prevented by SNAP. Further, IS stimulated activation of myosin light chain (MLC), potentially stimulating endothelial contractility, while SNAP decreased MLC activation. Thus, we conclude that the negative effects of IS on endothelial cells are prevented, to a major extent, by NO, via its divergent actions on ERK MAP kinase and MLC.
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Registered trials
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