ArticleFree radical biology & medicine2021
Hemopexin dosing improves cardiopulmonary dysfunction in murine sickle cell disease.
Article in Free radical biology & medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- Macrophages Contribute to Pulmonary Hypertension Associated With Sickle Cell Disease.Pulmonary circulation · 2026Article
- Extracellular Hemoglobin, Hypoxia, and Macrophage-Mediated Pulmonary Vascular Remodeling in Hemolytic Disease.International journal of molecular sciences · 2026Review
- Hemopexin Purification From Human Cohn Fraction IV Paste and Its Biophysical Characterization and Functional Evaluation in Sickle Cell Disease Mice.Biotechnology and bioengineering · 2026Article
- Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Review
- Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.EBioMedicine · 2026Review
- Ferroportin inhibition attenuates pulmonary hypertension in hypoxic sickle cell disease mice.Blood advances · 2026Article
- Heme Modulates Bladder Contractility Through the HO-CO-sGC-cGMP Pathway: Insights into Sickle Cell Disease-Associated Bladder Dysfunction.Antioxidants (Basel, Switzerland) · 2025Article
- Combined haptoglobin and hemopexin therapy for the treatment of cardiopulmonary dysfunction in sickle cell disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Transferrin Purification, Biophysical Characterization, and Lung Biodistribution in Sickle Cell Disease Mice.Biotechnology and bioengineering · 2025Article
- Innovations in Drug Discovery for Sickle Cell Disease Targeting Oxidative Stress and NRF2 Activation-A Short Review.International journal of molecular sciences · 2025Review
- Targeting lung heme iron by aerosol hemopexin adminstration in sickle cell disease pulmonary hypertension.Free radical biology & medicine · 2025Article
- Increased exercise tolerance in humanized G6PD-deficient mice.Blood advances · 2025Article
- Circulating free heme induces cytokine storm and pulmonary hypertension through the MKK3/p38 axis.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Targeting heme in sickle cell disease: new perspectives on priapism treatment.Frontiers in physiology · 2024Review
- In vivo evaluation of the effect of sickle cell hemoglobin S, C and therapeutic transfusion on erythrocyte metabolism and cardiorenal dysfunction.American journal of hematology · 2023Article
- The Role of Inflammation in The Cellular and Molecular Mechanisms of Cardiopulmonary Complications of Sickle Cell Disease.Biomolecules · 2023Review
- Moderate hypoxia induces metabolic divergence in circulating monocytes and tissue resident macrophages from Berkeley sickle cell anemia mice.Frontiers in medicine · 2023Article
- Metabolic correlates to critical speed in murine models of sickle cell disease.Frontiers in physiology · 2023Article
- Double-edged functions of hemopexin in hematological related diseases: from basic mechanisms to clinical application.Frontiers in immunology · 2023Review
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Authors and funding
20 authors at 9 institutions in 3 countries.
Funding
Abstract
Hemopexin (Hpx) is a crucial defense protein against heme liberated from degraded hemoglobin during hemolysis. High heme stress creates an imbalance in Hpx bioavailability, favoring heme accumulation and downstream pathophysiological responses leading to cardiopulmonary disease progression in sickle cell disease (SCD) patients. Here, we evaluated a model of murine SCD, which was designed to accelerate red blood cell sickling, pulmonary hypertension, right ventricular dysfunction, and exercise intolerance by exposure of the mice to moderate hypobaric hypoxia. The sequence of pathophysiology in this model tracks with circulatory heme accumulation, lipid oxidation, extensive remodeling of the pulmonary vasculature, and fibrosis. We hypothesized that Hpx replacement for an extended period would improve exercise tolerance measured by critical speed as a clinically meaningful therapeutic endpoint. Further, we sought to define the effects of Hpx on upstream cardiopulmonary function, histopathology, and tissue oxidation. Our data shows that tri-weekly administrations of Hpx for three months dose-dependently reduced heme exposure and pulmonary hypertension while improving cardiac pressure-volume relationships and exercise tolerance. Furthermore, Hpx administration dose-dependently attenuated pulmonary fibrosis and oxidative modifications in the lung and myocardium of the right ventricle. Observations in our SCD murine model are consistent with pulmonary vascular and right ventricular pathology at autopsy in SCD patients having suffered from severe pulmonary hypertension, right ventricular dysfunction, and sudden cardiac death. This study provides a translational evaluation supported by a rigorous outcome analysis demonstrating therapeutic proof-of-concept for Hpx replacement in SCD.
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Registered trials
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