ArticleBlood2013
MP4CO, a pegylated hemoglobin saturated with carbon monoxide, is a modulator of HO-1, inflammation, and vaso-occlusion in transgenic sickle mice.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01925001 (A Phase 2 Multi-center, Randomized, Double-blind, Comparator-Controlled Dose Finding Study to Evaluate MP4CO for the Acute Treatment of Vaso-occlusive Crises in Subjects With Sickle Cell Disease), which is not on this map. Cited by 44 papers, 1 of them a synthesis 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 Phase 2 Multi-center, Randomized, Double-blind, Comparator-Controlled Dose Finding Study to Evaluate MP4CO for the Acute Treatment of Vaso-occlusive Crises in Subjects With Sickle Cell Disease
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Pooled it
- Protein Arginine Methyltransferases in γ-Globin Regulation and Sickle Cell Disease: Emerging Connections to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- Kehuang capsule inhibits MAPK and AKT signaling pathways to mitigate CClLiver research (Beijing, China) · 2024Article
- Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.Journal of the American Heart Association · 2024Article
- The clinical relevance of heme detoxification by the macrophage heme oxygenase system.Frontiers in immunology · 2024Review
- Keap1-Nrf2 Heterodimer: A Therapeutic Target to Ameliorate Sickle Cell Disease.Antioxidants (Basel, Switzerland) · 2023Review
- The m6A reader YTHDF3-mediated PRDX3 translation alleviates liver fibrosis.Redox biology · 2022Article
- Article
- Vasculo-toxic and pro-inflammatory action of unbound haemoglobin, haem and iron in transfusion-dependent patients with haemolytic anaemias.British journal of haematology · 2021Article
- Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (HInternational journal of molecular sciences · 2020Review
- Article
- Artificial Blood: The History and Current Perspectives of Blood Substitutes.Discoveries (Craiova, Romania) · 2020Review
- The multifaceted role of ischemia/reperfusion in sickle cell anemia.The Journal of clinical investigation · 2020Review
- Drug Therapies for the Management of Sickle Cell Disease.F1000Research · 2020Review
- The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease.Mediterranean journal of hematology and infectious diseases · 2020Review
- Mechanisms of Toxicity and Modulation of Hemoglobin-based Oxygen Carriers.Shock (Augusta, Ga.) · 2019Review
- Circadian period 2: a missing beneficial factor in sickle cell disease by lowering pulmonary inflammation, iron overload, and mortality.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Critical role of C5a in sickle cell disease.American journal of hematology · 2019Article
- Therapeutic strategies for sickle cell disease: towards a multi-agent approach.Nature reviews. Drug discovery · 2019Review
- Pathophysiology of Sickle Cell Disease.Annual review of pathology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Transgenic sickle mice expressing β(S) hemoglobin have activated vascular endothelium in multiple organs that exhibits enhanced expression of NF-ĸB and adhesion molecules and promotes microvascular stasis in sickle, but not normal, mice in response to hypoxia/reoxygenation (H/R), or heme. Induction of heme oxygenase-1 (HO-1) or administration of its products, carbon monoxide (CO) or biliverdin, inhibits microvascular stasis in sickle mice. Infusion of human hemoglobin conjugated with polyethylene glycol and saturated with CO (MP4CO) markedly induced hepatic HO-1 activity and inhibited NF-ĸB activation and H/R-induced microvascular stasis in sickle mice. These effects were mediated by CO; saline or MP4 saturated with O2 (MP4OX) had little to no effect on H/R-induced stasis, though unmodified oxyhemoglobin exacerbated stasis. The HO-1 inhibitor, tin protoporphyrin, blocked MP4CO protection, consistent with HO-1 involvement in the protection afforded by MP4CO. MP4CO also induced nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), an important transcriptional regulator of HO-1 and other antioxidant genes. In a heterozygous (hemoglobin-AS) sickle mouse model, intravenous hemin induced cardiovascular collapse and mortality within 120 minutes, which was significantly reduced by MP4CO, but not MP4OX. These data demonstrate that MP4CO induces cytoprotective Nrf2 and HO-1 and decreases NF-ĸB activation, microvascular stasis, and mortality in transgenic sickle mouse models.
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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.