ArticleProceedings of the National Academy of Sciences of the United States of America2001
Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
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Who cites it
151 citing papers in PubMed, 383 citations in OpenAlex.
- Arginine Therapy for Pain in Sickle Cell Disease: A Phase-2 Randomized, Placebo-Controlled Trial.American journal of hematology · 2025Trial
- A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children.Blood · 2015Trial
- A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes.Haematologica · 2013Trial
- Laboratory and echocardiography markers in sickle cell patients with leg ulcers.American journal of hematology · 2011Trial
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- Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease.Free radical biology & medicine · 2005Trial
- CT Features of Sickle Cell Disease-Associated Pulmonary Hypertension.Journal of clinical medicine · 2026Article
- Extracellular Hemoglobin, Hypoxia, and Macrophage-Mediated Pulmonary Vascular Remodeling in Hemolytic Disease.International journal of molecular sciences · 2026Review
- Apohemoglobin-haptoglobin complex is a therapeutic against vaso-occlusive crisis: scavenging of hemoglobin and heme.Blood advances · 2026Article
- Angiotensin signaling is essential for stress erythropoiesis but causes retention of dysfunctional mitochondria in RBCs.JCI insight · 2026Article
- Crosstalk Between Sickle Cell Disease and Ferroptosis.International journal of molecular sciences · 2025Review
- The Redox Process in Red Blood Cells: Balancing Oxidants and Antioxidants.Antioxidants (Basel, Switzerland) · 2024Review
- Soluble guanylate cyclase stimulators and activators: new horizons in the treatment of priapism associated with sickle cell disease.Frontiers in pharmacology · 2024Review
- Oxidative Stress in Healthy and Pathological Red Blood Cells.Biomolecules · 2023Review
- Xanthine oxidase mediates chronic stress-induced cerebrovascular dysfunction and cognitive impairment.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura.Critical care (London, England) · 2023Observational
- Human Plasma Xanthine Oxidoreductase Activity in Cardiovascular Disease: Evidence from a Population-Based Study.Biomedicines · 2023Review
- Leg Ulcers in Sickle Cell Disease: A Multifactorial Analysis Highlights the Hemolytic Profile.Hematology reports · 2023Article
- The oral ferroportin inhibitor vamifeport improves hemodynamics in a mouse model of sickle cell disease.Blood · 2022Article
91 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Plasma xanthine oxidase (XO) activity was defined as a source of enhanced vascular superoxide (O(2)( *-)) and hydrogen peroxide (H(2)O(2)) production in both sickle cell disease (SCD) patients and knockout-transgenic SCD mice. There was a significant increase in the plasma XO activity of SCD patients that was similarly reflected in the SCD mouse model. Western blot and enzymatic analysis of liver tissue from SCD mice revealed decreased XO content. Hematoxylin and eosin staining of liver tissue of knockout-transgenic SCD mice indicated extensive hepatocellular injury that was accompanied by increased plasma content of the liver enzyme alanine aminotransferase. Immunocytochemical and enzymatic analysis of XO in thoracic aorta and liver tissue of SCD mice showed increased vessel wall and decreased liver XO, with XO concentrated on and in vascular luminal cells. Steady-state rates of vascular O(2)( *-) production, as indicated by coelenterazine chemiluminescence, were significantly increased, and nitric oxide (( *)NO)-dependent vasorelaxation of aortic ring segments was severely impaired in SCD mice, implying oxidative inactivation of ( *)NO. Pretreatment of aortic vessels with the superoxide dismutase mimetic manganese 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin markedly decreased O(2)( small middle dot-) levels and significantly restored acetylcholine-dependent relaxation, whereas catalase had no effect. These data reveal that episodes of intrahepatic hypoxia-reoxygenation associated with SCD can induce the release of XO into the circulation from the liver. This circulating XO can then bind avidly to vessel luminal cells and impair vascular function by creating an oxidative milieu and catalytically consuming (*)NO via O(2)( small middle dot-)-dependent mechanisms.
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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.