ArticlePloS one2018
Haptoglobin and hemopexin inhibit vaso-occlusion and inflammation in murine sickle cell disease: Role of heme oxygenase-1 induction.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 110 citations in OpenAlex.
- Lactate dehydrogenase to carboxyhemoglobin ratio as a biomarker of heme release to heme processing is associated with higher tricuspid regurgitant jet velocity and early death in sickle cell disease.American journal of hematology · 2021Trial
- Comment on: Heme, the HO-CO-sGC-cGMP pathway, and corpus cavernosum contractility: new insights into the pathophysiology of priapism in sickle cell disease.International journal of impotence research · 2026Article
- Apohemoglobin-haptoglobin complex is a therapeutic against vaso-occlusive crisis: scavenging of hemoglobin and heme.Blood advances · 2026Article
- Genetics and Genomics in Sickle Cell Disease in Africa.American journal of hematology · 2026Review
- Sustained expression of hemopexin in an animal model of sickle cell anemia.Blood vessels, thrombosis & hemostasis · 2026Article
- Plasma heme pool compartmentalization is linked to pathophysiology in Sickle Cell Disease.PloS one · 2026Article
- Elevated serum heme oxygenase-1 in pediatric sickle cell disease: Insights from the SickleGenAfrica Network.HemaSphere · 2025Article
- Innovations in Drug Discovery for Sickle Cell Disease Targeting Oxidative Stress and NRF2 Activation-A Short Review.International journal of molecular sciences · 2025Review
- Transsulfuration pathway activation attenuates oxidative stress and ferroptosis in sickle primary erythroblasts and transgenic mice.Communications biology · 2025Article
- Inflammatory profiling and immune cell infiltration in dysthyroid optic neuropathy: insights from bulk RNA sequencing.Frontiers in immunology · 2025Article
- Iron, Oxidative Stress, and Haptoglobin Gene Polymorphism in Sickle Cell Disease Patients With Inflammation in Cameroon: An Analytical Cross-Sectional Study.Biochemistry research international · 2025Article
- Is Hemopexin a Nephrotoxin or a Marker of Kidney Injury in Renal Ischemia-Reperfusion?Biomolecules · 2024Article
- Coadministration of PEGylated apohemoglobin and haptoglobin can limit vascular dysfunction in the microcirculation and prevent acute inflammation.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- Toxic side-effects of diaspirin cross-linked human hemoglobin are attenuated by the apohemoglobin-haptoglobin complex.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Cell-Free Hemoglobin in the Pathophysiology of Trauma: A Scoping Review.Critical care explorations · 2024Article
- Red blood cell-derived materials for cancer therapy: Construction, distribution, and applications.Materials today. Bio · 2024Review
- Targeting heme in sickle cell disease: new perspectives on priapism treatment.Frontiers in physiology · 2024Review
- Haptoglobin buffers lipopolysaccharides to delay activation of NFκB.Frontiers in immunology · 2024Article
- Circulating biomarkers associated with pediatric sickle cell disease.Frontiers in molecular biosciences · 2024Article
- From Stress to Sick(le) and Back Again-Oxidative/Antioxidant Mechanisms, Genetic Modulation, and Cerebrovascular Disease in Children with Sickle Cell Anemia.Antioxidants (Basel, Switzerland) · 2023Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. Plasma haptoglobin and hemopexin scavenge free hemoglobin and heme, respectively, but can be depleted in hemolytic states. Haptoglobin and hemopexin supplementation protect tissues, including the vasculature, liver and kidneys. It is widely assumed that these protective effects are due primarily to hemoglobin and heme clearance from the vasculature. However, this simple assumption does not account for the consequent cytoprotective adaptation seen in cells and organs. To further address the mechanism, we used a hyperhemolytic murine model (Townes-SS) of sickle cell disease to examine cellular responses to haptoglobin and hemopexin supplementation. A single infusion of haptoglobin or hemopexin (± equimolar hemoglobin) in SS-mice increased heme oxygenase-1 (HO-1) in the liver, kidney and skin several fold within 1 hour and decreased nuclear NF-ĸB phospho-p65, and vaso-occlusion for 48 hours after infusion. Plasma hemoglobin and heme levels were not significantly changed 1 hour after infusion of haptoglobin or hemopexin. Haptoglobin and hemopexin also inhibited hypoxia/reoxygenation and lipopolysaccharide-induced vaso-occlusion in SS-mice. Inhibition of HO-1 activity with tin protoporphyrin blocked the protections afforded by haptoglobin and hemopexin in SS-mice. The HO-1 reaction product carbon monoxide, fully restored the protection, in part by inhibiting Weibel-Palade body mobilization of P-selectin and von Willebrand factor to endothelial cell surfaces. Thus, the mechanism by which haptoglobin and hemopexin supplementation in hyperhemolytic SS-mice induces cytoprotective cellular responses is linked to increased HO-1 activity.
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Registered trials
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