ArticlePloS one2011
Global gene expression profiling of endothelium exposed to heme reveals an organ-specific induction of cytoprotective enzymes in sickle cell disease.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Role of innate immunity-triggered pathways in the pathogenesis of Sickle Cell Disease: a meta-analysis of gene expression studies.Scientific reports · 2015Pooled it
- Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor.Blood · 2014Trial
- Long Non-Coding RNA MALAT1 Regulates HMOX1 in Sickle Cell Disease-Associated Pulmonary Hypertension.Cells · 2026Article
- Article
- Heme Burden and Ensuing Mechanisms That Protect the Kidney: Insights from Bench and Bedside.International journal of molecular sciences · 2021Review
- Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases.International journal of molecular sciences · 2021Review
- PPARγ increases HUWE1 to attenuate NF-κB/p65 and sickle cell disease with pulmonary hypertension.Blood advances · 2021Article
- Smooth muscle cytochrome b5 reductase 3 deficiency accelerates pulmonary hypertension development in sickle cell mice.Blood advances · 2019Article
- Hemoglobin alters vitamin carrier uptake and vitamin D metabolism in proximal tubule cells: implications for sickle cell disease.American journal of physiology. Cell physiology · 2019Article
- Nrf2 activation in myeloid cells and endothelial cells differentially mitigates sickle cell disease pathology in mice.Blood advances · 2019Article
- Sleep phenotype in the Townes mouse model of sickle cell disease.Sleep & breathing = Schlaf & Atmung · 2019Article
- Mechanisms of NRF2 activation to mediate fetal hemoglobin induction and protection against oxidative stress in sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Contribution of alternative complement pathway to delayed hemolytic transfusion reaction in sickle cell disease.Haematologica · 2018Article
- Loss of NRF2 function exacerbates the pathophysiology of sickle cell disease in a transgenic mouse model.Blood · 2018Article
- Peroxisome Proliferator-Activated Receptor γ Regulates the V-Ets Avian Erythroblastosis Virus E26 Oncogene Homolog 1/microRNA-27a Axis to Reduce Endothelin-1 and Endothelial Dysfunction in the Sickle Cell Mouse Lung.American journal of respiratory cell and molecular biology · 2017Article
- Heme Oxygenase-1 in Kidney Health and Disease.Antioxidants & redox signaling · 2016Review
- Genetic variants and cell-free hemoglobin processing in sickle cell nephropathy.Haematologica · 2015Article
- Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders.Frontiers in physiology · 2015Review
- Extracellular hemin crisis triggers acute chest syndrome in sickle mice.The Journal of clinical investigation · 2013Article
- Gene-centric association study of acute chest syndrome and painful crisis in sickle cell disease patients.Blood · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSickle cell disease (SCD) is characterized by hemolysis, vaso-occlusion and ischemia reperfusion injury. These events cause endothelial dysfunction and vasculopathies in multiple systems. However, the lack of atherosclerotic lesions has led to the idea that there are adaptive mechanisms that protect the endothelium from major vascular insults in SCD patients. The molecular bases for this phenomenon are poorly defined. This study was designed to identify the global profile of genes induced by heme in the endothelium, and assess expression of the heme-inducible cytoprotective enzymes in major organs impacted by SCD. METHODS AND
findingsTotal RNA isolated from heme-treated endothelial monolayers was screened with the Affymetrix U133 Plus 2.0 chip, and the microarray data analyzed using multiple bioinformatics software. Hierarchical cluster analysis of significantly differentially expressed genes successfully segregated heme and vehicle-treated endothelium. Validation studies showed that the induction of cytoprotective enzymes by heme was influenced by the origin of endothelial cells, the duration of treatment, as well as the magnitude of induction of individual enzymes. In agreement with these heterogeneities, we found that induction of two major Nrf2-regulated cytoprotective enzymes, heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1 is organ-specific in two transgenic mouse models of SCD. This data was confirmed in the endothelium of post-mortem lung tissues of SCD patients.
conclusionsIndividual organ systems induce unique profiles of cytoprotective enzymes to neutralize heme in SCD. Understanding this heterogeneity may help to develop effective therapies to manage vasculopathies of individual systems.
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.