ArticleISRN oxidative medicine2013
Vasculotoxic and Proinflammatory Effects of Plasma Heme: Cell Signaling and Cytoprotective Responses.
Article in ISRN oxidative medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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.
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Who cites it
43 citing papers in PubMed, 55 citations in OpenAlex.
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- Selective AMPKβ1 activation induces fetal hemoglobin in human erythroid cells and sickle cell mice via the noncanonical NRF2 pathway.Science advances · 2025Article
- Leveraging Artificial Intelligence and Modulation of Oxidative Stressors to Enhance Healthspan and Radical Longevity.Biomolecules · 2025Review
- Is Hemopexin a Nephrotoxin or a Marker of Kidney Injury in Renal Ischemia-Reperfusion?Biomolecules · 2024Article
- Cell-Free Hemoglobin in the Pathophysiology of Trauma: A Scoping Review.Critical care explorations · 2024Article
- Heme Proteins and Kidney Injury: Beyond Rhabdomyolysis.Kidney360 · 2022Review
- MASP-2 and MASP-3 inhibitors block complement activation, inflammation, and microvascular stasis in a murine model of vaso-occlusion in sickle cell disease.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Crosstalk between Heme Oxygenase-1 and Iron Metabolism in Macrophages: Implications for the Modulation of Inflammation and Immunity.Antioxidants (Basel, Switzerland) · 2022Review
- Heme stimulates platelet mitochondrial oxidant production to induce targeted granule secretion.Redox biology · 2021Article
- Non-Transferrin-Bound Iron in the Spotlight: Novel Mechanistic Insights into the Vasculotoxic and Atherosclerotic Effect of Iron.Antioxidants & redox signaling · 2021Review
- Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and nonpulmonary organ dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Cardiac pathophysiology in sickle cell disease.Journal of thrombosis and thrombolysis · 2021Review
- Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression.Scientific reports · 2021Observational
- Vasculo-toxic and pro-inflammatory action of unbound haemoglobin, haem and iron in transfusion-dependent patients with haemolytic anaemias.British journal of haematology · 2021Article
- Cas9-AAV6 gene correction of beta-globin in autologous HSCs improves sickle cell disease erythropoiesis in mice.Nature communications · 2021Article
- Atomistic Simulations of Heme Dissociation Pathways in Human Methemoglobins Reveal Hidden Intermediates.Biochemistry · 2020Article
- The Interplay between Molten Globules and Heme Disassociation Defines Human Hemoglobin Disassembly.Biophysical journal · 2020Article
- Antithrombotic effects of heme-degrading and heme-binding proteins.American journal of physiology. Heart and circulatory physiology · 2020Article
- Article
- Critical role of C5a in sickle cell disease.American journal of hematology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The proinfammatory vasculotoxic effects of intravascular hemolysis are modulated by plasma hemoglobin and heme clearance via the haptoglobin/CD163 system and the hemopexin/CD91 system, respectively, and detoxification through the heme oxygenase/ferritin system. However, sudden or excessive hemolysis can overwhelm these protective systems leading to heme interacting with cells of the vasculature. Heme presents a damage-associated molecular pattern to the innate immune system. Heme is an extracellular inflammatory signaling molecule with strict binding specificity for TLR4 on monocyte/macrophages, endothelial, and other cells. The resulting TLR4 signaling cascade rapidly leads to intracellular oxidative stress and an inflammatory response. Heme also induces a cytoprotective response that includes Nrf2 responsive genes such as heme oxygenase-1, ferritin, haptoglobin, hemopexin, and other antioxidant response genes. It is the balance between the pro-inflammatory/vasculotoxic effects of plasma hemoglobin/heme and the cytoprotective responses that ultimately determines the pathophysiologic outcome in patients.
Identifiers
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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.