ReviewCurrent molecular medicine2008
Nitric oxide and arginine dysregulation: a novel pathway to pulmonary hypertension in hemolytic disorders.
Review in Current molecular medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- The Relevance of Endothelial Dysfunction Biomarkers in Thalassemia Patients and Healthy Individuals: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- B-type natriuretic peptide and plasma hemoglobin levels following transfusion of shorter-storage versus longer-storage red blood cells: Results from the TOTAL randomized trial.American heart journal · 2017Trial
- 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
- Red blood cell-derived arginase release in hemolytic uremic syndrome.Journal of translational medicine · 2024Article
- Arginine supplementation improves lactate dehydrogenase levels in steady-state sickle cell patients: preliminary findings from Kinshasa, the Democratic Republic of Congo.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- The Effect of L-Arginine Oral Supplementation on the Improvement of Cardiovascular Function and Pulmonary Artery Pressure in Patients with Major and Intermedia β-Thalassemia.Iranian journal of public health · 2023Article
- Myeloid-derived suppressor cells and pulmonary hypertension.Frontiers in immunology · 2023Review
- Nitric Oxide Modulates Metabolic Processes in the Tumor Immune Microenvironment.International journal of molecular sciences · 2021Review
- Hydroxyurea improves nitric oxide bioavailability in humanized sickle cell mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Gamma heavy chain disease complicated by pulmonary hypertension, which was successfully treated with lenalidomide.BMJ case reports · 2020Article
- Altered Gut Microbiome Profile in Patients With Pulmonary Arterial Hypertension.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Sickle cell disease subjects and mouse models have elevated nitrite and cGMP levels in blood compartments.Nitric oxide : biology and chemistry · 2020Article
- Are thalassemia patients oxidatively challenged?Medical journal, Armed Forces India · 2019Article
- The role of nitrite in muscle function, susceptibility to contraction injury, and fatigability in sickle cell mice.Nitric oxide : biology and chemistry · 2018Article
- Correlates of Pulmonary Function in Children with Sickle Cell Disease and Elevated Fetal Hemoglobin.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2018Article
- The role of carbon monoxide and heme oxygenase in the prevention of sickle cell disease vaso-occlusive crises.American journal of hematology · 2017Review
- Hematological disorders and pulmonary hypertension.World journal of cardiology · 2016Review
- Arginase Inhibition Reverses Endothelial Dysfunction, Pulmonary Hypertension, and Vascular Stiffness in Transgenic Sickle Cell Mice.Anesthesia and analgesia · 2016Article
- Evaluation of carotid artery dynamics & correlation with cardiac & hepatic iron in β-thalassaemia patients.The Indian journal of medical research · 2016Article
- Influence of βS-Globin Haplotypes and Hydroxyurea on Arginase I Levels in Sickle Cell Disease.Disease markers · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Secondary pulmonary hypertension (PH) is emerging as one of the leading causes of mortality and morbidity in patients with hemolytic anemias such as sickle cell disease (SCD) and thalassemia. Impaired nitric oxide (NO) bioavailability represents the central feature of endothelial dysfunction, and is a major factor in the pathophysiology of PH. Inactivation of NO correlates with hemolytic rate and is associated with the erythrocyte release of cell-free hemoglobin, which consumes NO directly, and the simultaneous release of the arginine-metabolizing enzyme arginase, which limits bioavailability of the NO synthase substrate arginine during the process of intravascular hemolysis. Rapid consumption of NO is accelerated by oxygen radicals that exists in both SCD and thalassemia. A dysregulation of arginine metabolism contributes to endothelial dysfunction and PH in SCD, and is strongly associated with prospective patient mortality. The central mechanism responsible for this metabolic disorder is enhanced arginine turnover, occurring secondary to enhanced plasma arginase activity. This is consistent with a growing appreciation of the role of excessive arginase activity in human diseases, including asthma and pulmonary arterial hypertension. New treatments aimed at improving arginine and NO bioavailability through arginase inhibition, suppression of hemolytic rate, oral arginine supplementation, or use of NO donors represent potential therapeutic strategies for this common pulmonary complication of hemolytic disorders.
Indexed as
Identifiers
What OpenQuestion holds
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.