ArticleThe Journal of clinical investigation2003
Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 115 citations in OpenAlex.
- Cardiovascular-kidney-metabolic syndrome through the lens of gut‑derived uremic toxins.Gut microbes · 2026Review
- Phenylacetic Acid, a Gut Microbially Produced Metabolite, Reduces Atherosclerosis Burden and Impacts Host Lipid Homeostasis.Journal of the American Heart Association · 2026Article
- Metabolomic alterations in human brain microvascular endothelial cells induced by traumatic injury.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Phenylacetic acid catabolism modulates virulence factors and drug resistance in Acinetobacter baumannii MCC 2076.World journal of microbiology & biotechnology · 2025Article
- Association between renal function and arterial stiffness among women with systemic lupus erythematosus or antiphospholipid syndrome.Cardiology journal · 2025Article
- Exposome and Metabolome Analysis of Sugarcane Workers Reveals Predictors of Kidney Injury.Kidney international reports · 2024Article
- Metabolomics highlights biochemical perturbations occurring in the kidney and liver of mice administered a human dose of colistin.Frontiers in molecular biosciences · 2024Article
- Detailing Protein-Bound Uremic Toxin Interaction Mechanisms with Human Serum Albumin in the Pursuit of Designing Competitive Binders.International journal of molecular sciences · 2023Review
- Review
- Patient Stratification in Sepsis: Using Metabolomics to Detect Clinical Phenotypes, Sub-Phenotypes and Therapeutic Response.Metabolites · 2022Review
- Prevention of vascular calcification by the endogenous chromogranin A-derived mediator that inhibits osteogenic transdifferentiation.Basic research in cardiology · 2021Article
- Aromatic amino acids play a harmonizing role in prostate cancer: A metabolomics-based cross-sectional study.International journal of reproductive biomedicine · 2021Article
- Salivary metabolites associated with a 5-year tooth loss identified in a population-based setting.BMC medicine · 2021Article
- Uremic Toxins and Their Relation with Oxidative Stress Induced in Patients with CKD.International journal of molecular sciences · 2021Review
- Gut-Derived Metabolite Indole-3-Propionic Acid Modulates Mitochondrial Function in Cardiomyocytes and Alters Cardiac Function.Frontiers in medicine · 2021Article
- Gut-Derived Protein-Bound Uremic Toxins.Toxins · 2020Review
- Uremic Toxins and Ciprofloxacin Affect Human Tenocytes In Vitro.International journal of molecular sciences · 2020Article
- Monocytes in Uremia.Toxins · 2020Review
- Novel plasma peptide markers involved in the pathology of CKD identified using mass spectrometric approach.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NO prevents atherogenesis and inflammation in vessel walls by inhibition of cell proliferation and cytokine-induced endothelial expression of adhesion molecules and proinflammatory cytokines. Reduced NO production due to inhibition of either eNOS or iNOS may therefore reinforce atherosclerosis. Patients with end-stage renal failure show markedly increased mortality due to atherosclerosis. In the present study we tested the hypothesis that uremic toxins are responsible for reduced iNOS expression. LPS-induced iNOS expression in mononuclear leukocytes was studied using real-time PCR. The iNOS expression was blocked by addition of plasma from patients with end-stage renal failure, whereas plasma from healthy controls had no effect. Hemofiltrate obtained from patients with end-stage renal failure was fractionated by chromatographic methods. The chromatographic procedures revealed a homogenous fraction that inhibits iNOS expression. Using gas chromatography/mass spectrometry, this inhibitor was identified as phenylacetic acid. Authentic phenylacetic acid inhibited iNOS expression in a dose-dependent manner. In healthy control subjects, plasma concentrations were below the detection level, whereas patients with end-stage renal failure had a phenylacetic acid concentration of 3.49 +/- 0.33 mmol/l (n = 41). It is concluded that accumulation of phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. That mechanism may contribute to increased atherosclerosis and cardiovascular morbidity in patients with end-stage renal failure.
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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.