ArticleRedox biology2017
Potential therapeutic action of nitrite in sickle cell disease.
Article in Redox biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Sickle cell microvascular paradox-oxygen supply-demand mismatch.American journal of hematology · 2019Trial
- Nitrosyl hemoglobin formation from nitrite in normal and sickle blood.Free radical biology & medicine · 2024Article
- Thiol-catalyzed formation of NO-ferroheme regulates intravascular NO signaling.Nature chemical biology · 2023Article
- Nitrite decreases sickle hemoglobin polymerization in vitro independently of methemoglobin formation.Toxicology and applied pharmacology · 2023Article
- The Role of Oxidants in Percutaneous Coronary Intervention-Induced Endothelial Dysfunction: Can We Harness Redox Signaling to Improve Clinical Outcomes?Antioxidants & redox signaling · 2023Review
- Thiol catalyzed formation of NO-ferroheme regulates canonical intravascular NO signaling.Research square · 2023Article
- Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and nonpulmonary organ dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Pulmonary Arterial Hypertension: Diagnosis, Treatment, and Novel Advances.American journal of respiratory and critical care medicine · 2021Article
- Red Blood Cell-Mediated S-Nitrosohemoglobin-Dependent Vasodilation: Lessons Learned from a β-Globin Cys93 Knock-In Mouse.Antioxidants & redox signaling · 2021Review
- Effects of nitrite and far-red light on coagulation.Nitric oxide : biology and chemistry · 2021Article
- The effect of dietary nitrate supplementation on the speed-duration relationship in mice with sickle cell disease.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- Intravascular hemolysis triggers ADP-mediated generation of platelet-rich thrombi in precapillary pulmonary arterioles.JCI insight · 2020Article
- Sickle cell disease subjects and mouse models have elevated nitrite and cGMP levels in blood compartments.Nitric oxide : biology and chemistry · 2020Article
- Electrical Impedance Characterization of Erythrocyte Response to Cyclic Hypoxia in Sickle Cell Disease.ACS sensors · 2019Article
- Hemoglobin β93 Cysteine Is Not Required for Export of Nitric Oxide Bioactivity From the Red Blood Cell.Circulation · 2019Article
- Ischemia-Reperfusion Injury in Sickle Cell Disease: From Basics to Therapeutics.The American journal of pathology · 2019Review
- cGMP modulation therapeutics for sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Erythrocytic bioactivation of nitrite and its potentiation by far-red light.Redox biology · 2019Article
- Nitrite and nitrate chemical biology and signalling.British journal of pharmacology · 2019Review
- Inflammation in sickle cell disease.Clinical hemorheology and microcirculation · 2018Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes under hypoxic conditions, increasing rigidity, fragility, calcium influx-mediated dehydration, and adhesivity of red blood cells. Increased red cell fragility results in hemolysis, which reduces nitric oxide (NO) bioavailability, and induces platelet activation and inflammation leading to adhesion of circulating blood cells. Nitric Oxide inhibits adhesion and platelet activation. Nitrite has emerged as an attractive therapeutic agent that targets delivery of NO activity to areas of hypoxia through bioactivation by deoxygenated red blood cell hemoglobin. In this study, we demonstrate anti-platelet activity of nitrite at doses achievable through dietary interventions with comparison to similar doses with other NO donating agents. Unlike other NO donating agents, nitrite activity is shown to be potentiated in the presence of red blood cells in hypoxic conditions. We also show that nitrite reduces calcium associated loss of phospholipid asymmetry that is associated with increased red cell adhesion, and that red cell deformability is also improved. We show that nitrite inhibits red cell adhesion in a microfluidic flow-channel assay after endothelial cell activation. In further investigations, we show that leukocyte and platelet adhesion is blunted in nitrite-fed wild type mice compared to control after either lipopolysaccharide- or hemolysis-induced inflammation. Moreover, we demonstrate that nitrite treatment results in a reduction in adhesion of circulating blood cells and reduced red blood cell hemolysis in humanized transgenic sickle cell mice subjected to local hypoxia. These data suggest that nitrite is an effective anti-platelet and anti-adhesion agent that is activated by red blood cells, with enhanced potency under physiological hypoxia and in venous blood that may be useful therapeutically.
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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.