ArticleThe Journal of clinical investigation2008
Endothelin receptor antagonism prevents hypoxia-induced mortality and morbidity in a mouse model of sickle-cell disease.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03352986 (A Substudy of the CADRE Study), which is not on this map. Cited by 72 papers, 2 of them syntheses that pooled it.
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.
A Substudy of the CADRE Study: Determination of Clinical Markers in Patients With Extreme Sickle Cell Disease Phenotype
Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 133 citations in OpenAlex.
- Magnesium for treating sickle cell disease.The Cochrane database of systematic reviews · 2019Pooled it
- Magnesium for treating sickle cell disease.The Cochrane database of systematic reviews · 2017Pooled it
- Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor.Blood · 2014Trial
- Endothelium-derived endothelin-1 mediates sickle cell nephropathy.Function (Oxford, England) · 2026Article
- Endothelin receptor antagonism in sickle cell disease: Is the time now?Canadian journal of physiology and pharmacology · 2026Review
- 17(R)-Resolvin D1 protects against sickle cell-related inflammatory cardiomyopathy in humanized mice.Blood · 2025Article
- Prevalence and associated factors of glomerular hyperfiltration among adult stable sickle cells in Kinshasa, DR Congo.Renal failure · 2024Article
- Can we use biomarkers to identify those at risk of acute pain from sickle cell disease?Expert review of hematology · 2024Review
- Mouse models of sickle cell disease: Imperfect and yet very informative.Blood cells, molecules & diseases · 2024Review
- Autophagy protein 5 controls flow-dependent endothelial functions.Cellular and molecular life sciences : CMLS · 2023Article
- Evidence of protective effects of recombinant ADAMTS13 in a humanized model of sickle cell disease.Haematologica · 2022Article
- Monocrotaline-Induced Pulmonary Arterial Hypertension and Bosentan Treatment in Rats: Focus on Plasma and Erythrocyte Parameters.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Endothelin A receptor antagonist attenuated renal iron accumulation in iron overload heme oxygenase-1 knockout mice.Canadian journal of physiology and pharmacology · 2022Article
- Glomerular filtration rate abnormalities in sickle cell disease.Frontiers in medicine · 2022Review
- Mechanisms of pain in sickle cell disease.British journal of pain · 2021Article
- Endothelin-targeted new treatments for proteinuric and inflammatory glomerular diseases: focus on the added value to anti-renin-angiotensin system inhibition.Pediatric nephrology (Berlin, Germany) · 2021Review
- Mn porphyrins as a novel treatment targeting sickle cell NOXs to reverse and prevent acute vaso-occlusion in vivo.Blood advances · 2020Article
- Endothelin Receptor Antagonists: Status Quo and Future Perspectives for Targeted Therapy.Journal of clinical medicine · 2020Review
- Updated mechanisms underlying sickle cell disease-associated pain.Neuroscience letters · 2019Review
- Impact of ET-1 and sex in glomerular hyperfiltration in humanized sickle cell mice.Clinical science (London, England : 1979) · 2019Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with sickle-cell disease (SCD) suffer from tissue damage and life-threatening complications caused by vasoocclusive crisis (VOC). Endothelin receptors (ETRs) are mediators of one of the most potent vasoconstrictor pathways in mammals, but the relationship between vasoconstriction and VOC is not well understood. We report here that pharmacological inhibition of ETRs prevented hypoxia-induced acute VOC and organ damage in a mouse model of SCD. An in vivo ultrasonographic study of renal hemodynamics showed a substantial increase in endothelin-mediated vascular resistance during hypoxia/reoxygenation-induced VOC. This increase was reversed by administration of the dual ETR antagonist (ETRA) bosentan, which had pleiotropic beneficial effects in vivo. It prevented renal and pulmonary microvascular congestion, systemic inflammation, dense rbc formation, and infiltration of activated neutrophils into tissues with subsequent nitrative stress. Bosentan also prevented death of sickle-cell mice exposed to a severe hypoxic challenge. These findings in mice suggest that ETRA could be a potential new therapy for SCD, as it may prevent acute VOC and limit organ damage in sickle-cell patients.
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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.