ArticleAmerican journal of physiology. Heart and circulatory physiology2020
Apohemoglobin-haptoglobin complex attenuates the pathobiology of circulating acellular hemoglobin and heme.
Article in American journal of physiology. Heart and circulatory physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Evaluation of the Methemoglobin-Haptoglobin Protein Complex for Detoxification of Cyanide, Azide, and Sulfide in In Vitro Binding Models.Chemical research in toxicology · 2026Article
- Apohemoglobin-haptoglobin complex is a therapeutic against vaso-occlusive crisis: scavenging of hemoglobin and heme.Blood advances · 2026Article
- Hemoglobin binders reduce inflammation and tissue injury from hemolysis in venovenous extracorporeal circulation.Blood advances · 2026Article
- Mitigating hemoglobin-induced nephropathy: ApoHb-hp protection of podocytes.Physiological reports · 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
- Silk Fibroin Particles as Carriers in the Development of Hemoglobin-Based Oxygen Carriers.Advanced nanobiomed research · 2023Article
- Silk Fibroin Particles as Carriers in the Development of All-Natural Hemoglobin-Based Oxygen Carriers (HBOCs).bioRxiv : the preprint server for biology · 2023Article
- Apohemoglobin-haptoglobin complex alleviates iron toxicity in mice with β-thalassemia via scavenging of cell-free hemoglobin and heme.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Extracellular Hemoglobin: Modulation of Cellular Functions and Pathophysiological Effects.Biomolecules · 2022Review
- Increased hemoglobin affinity for oxygen with GBT1118 improves hypoxia tolerance in sickle cell mice.American journal of physiology. Heart and circulatory physiology · 2021Article
- Apohemoglobin-haptoglobin complexes attenuate the hypertensive response to low-molecular-weight polymerized hemoglobin.Blood advances · 2020Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Haptoglobin (Hp) is the plasma protein that binds and clears cell-free hemoglobin (Hb), whereas apohemoglobin (apoHb, i.e., Hb devoid of heme) can bind heme. Therefore, the apoHb-Hp protein complex should facilitate holoHb-apoHb αβ-dimer exchange and apoHb-heme intercalation. Thus, we hypothesized that apoHb-Hp could facilitate both Hb and heme clearance, which, if not alleviated, could have severe microcirculatory consequences. In this study, we characterized apoHb-Hp and Hb/heme ligand interactions and assessed their in vivo consequences. Hb exchange and heme binding with the apoHb-Hp complex was studied with transfer assays using size-exclusion high-performance liquid chromatography coupled with UV-visible spectrophotometry. Exchange/transfer experiments were conducted in guinea pigs dosed with Hb or heme-albumin followed by a challenge with equimolar amounts of apoHb-Hp. Finally, systemic and microcirculatory parameters were studied in hamsters instrumented with a dorsal window chamber via intravital microscopy. In vitro and in vivo Hb exchange and heme transfer experiments demonstrated proof-of-concept Hb/heme ligand transfer to apoHb-Hp. Dosing with the apoHb-Hp complex reversed Hb- and heme-induced systemic hypertension and microvascular vasoconstriction, reduced microvascular blood flow, and diminished functional capillary density. Therefore, this study highlights the apoHb-Hp complex as a novel therapeutic strategy to attenuate the adverse systemic and microvascular responses to intravascular Hb and heme exposure.
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