ArticleNature2012
Endothelial cell expression of haemoglobin α regulates nitric oxide signalling.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 201 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Screening for Alpha Globin Deletions
Collection of Human Biospecimens for Basic and Clinical Research Into Globin Variants
Does a Flashlight Used to Detect Pet Biological Fluids on Human Skin and Other Surfaces Increase Gas Phase Nitric Oxide Levels?
Who cites it
201 citing papers in PubMed, 309 citations in OpenAlex.
- Endothelial nitric oxide signaling in cellular and systemic metabolism.Redox biology · 2026Review
- Article
- A metabolic-epigenetic switch governs multicellular cardiac repair following succinate dehydrogenase inhibition.Nature cardiovascular research · 2026Article
- HIF1α-KLF4 signaling dictates extra-erythrocyte expression of hemoglobin conferring sorafenib resistance in hepatocellular carcinoma.Signal transduction and targeted therapy · 2026Article
- Research Progress on Hemoglobin Expression in Non-Erythroid Cells and Tumor Cells.Journal of cellular physiology · 2026Review
- Characterization of erythroblastic island and tissue macrophages using a novel CD169-tdTomato-Cre mouse model and scRNA-seq.Blood red cells & iron · 2026Article
- Smooth Muscle Cell Cytoglobin is a Negative Regulator of Atherosclerotic Fibrous Cap Development.bioRxiv : the preprint server for biology · 2026Article
- Gene Expression Profiles at Early vs Late Stages After Cervical Artery Dissection.Neurology. Genetics · 2026Article
- Cytochrome bBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- The Emerging Role of Endothelial Ion Channels in the Control of Human Microcirculation.International journal of molecular sciences · 2026Review
- Probing into the binding mechanism of phosphorus(V)-corrole with hemoglobin using photophysical and computational approach.Scientific reports · 2026Article
- Endothelial Cell Secretome Alterations Induced by Inflammatory Stress.bioRxiv : the preprint server for biology · 2026Article
- Single-cell transcriptomic analysis reveals age-related remodeling of brain endothelial cells.Aging brain · 2026Article
- NO- and S-nitrosothiols-dependent relaxation in large and small resistance blood vessels.Frontiers in physiology · 2026Review
- Arterial iron regulates vasodilation during anemia via endothelial holo-alpha globin.bioRxiv : the preprint server for biology · 2025Article
- Elastin Regulation of Vasoreactivity in Resistance Arteries.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Impact of Endothelial Diversity and Dysfunction on Cardiovascular Disease.Comprehensive Physiology · 2025Review
- Endothelial CYB5R3 couples store-operated calcium entry to TRPV2 activation and vascular fitness.bioRxiv : the preprint server for biology · 2025Article
- A narrative review of the distribution and role of multipotent fibroblasts in penile tissue: implications for regenerative medicine and erectile dysfunction.Translational andrology and urology · 2025Review
- Hemoglobin as a pseudoperoxidase and drug target for oxidative stress-related diseases.Signal transduction and targeted therapy · 2025Article
141 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Models of unregulated nitric oxide (NO) diffusion do not consistently account for the biochemistry of NO synthase (NOS)-dependent signalling in many cell systems. For example, endothelial NOS controls blood pressure, blood flow and oxygen delivery through its effect on vascular smooth muscle tone, but the regulation of these processes is not adequately explained by simple NO diffusion from endothelium to smooth muscle. Here we report a new model for the regulation of NO signalling by demonstrating that haemoglobin (Hb) α (encoded by the HBA1 and HBA2 genes in humans) is expressed in human and mouse arterial endothelial cells and enriched at the myoendothelial junction, where it regulates the effects of NO on vascular reactivity. Notably, this function is unique to Hb α and is abrogated by its genetic depletion. Mechanistically, endothelial Hb α haem iron in the Fe(3+) state permits NO signalling, and this signalling is shut off when Hb α is reduced to the Fe(2+) state by endothelial cytochrome b5 reductase 3 (CYB5R3, also known as diaphorase 1). Genetic and pharmacological inhibition of CYB5R3 increases NO bioactivity in small arteries. These data reveal a new mechanism by which the regulation of the intracellular Hb α oxidation state controls NOS signalling in non-erythroid cells. This model may be relevant to haem-containing globins in a broad range of NOS-containing somatic cells.
Indexed as
Identifiers
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.