ArticleCirculation research2011
Network for activation of human endothelial cells by oxidized phospholipids: a critical role of heme oxygenase 1.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.Nature genetics · 2016Pooled it
- UQCRB regulates mitochondrial energy metabolism by promoting COX5 A in atherosclerotic endothelial dysfunction.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Ox-LDL induces a non-inflammatory response enriched for coronary artery disease risk in human endothelial cells.Scientific reports · 2025Article
- Therapeutic implication of oxidative stress-induced growth inhibitor 1 (OSGIN1) in cancer.Oncogene · 2025Review
- TheBiomolecules · 2025Review
- Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers.Frontiers in cell and developmental biology · 2024Review
- Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling.International journal of molecular sciences · 2023Review
- Article
- Electronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative Biomarkers.Circulation research · 2021Article
- TGR5 protects against cholestatic liver disease via suppressing the NF-κB pathway and activating the Nrf2/HO-1 pathway.Annals of translational medicine · 2021Article
- Cholesterol-Induced Phenotypic Modulation of Smooth Muscle Cells to Macrophage/Fibroblast-like Cells Is Driven by an Unfolded Protein Response.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Heme Oxygenase-1 at the Nexus of Endothelial Cell Fate Decision Under Oxidative Stress.Frontiers in cell and developmental biology · 2021Article
- Gene networks and pathways for plasma lipid traits via multitissue multiomics systems analysis.Journal of lipid research · 2021Article
- Characterization of the 5'-flanking region of the human and mouse CHAC1 genes.Biochemistry and biophysics reports · 2020Article
- Molecular mechanisms of coronary disease revealed using quantitative trait loci for TCF21 binding, chromatin accessibility, and chromosomal looping.Genome biology · 2020Article
- Systems Genetics in Human Endothelial Cells Identifies Non-coding Variants Modifying Enhancers, Expression, and Complex Disease Traits.American journal of human genetics · 2020Article
- Saharan Dust Events in the Dust Belt -Canary Islands- and the Observed Association with in-Hospital Mortality of Patients with Heart Failure.Journal of clinical medicine · 2020Article
- Neutralization of Oxidized Phospholipids Ameliorates Non-alcoholic Steatohepatitis.Cell metabolism · 2020Article
- Systems genetics applications in metabolism research.Nature metabolism · 2019Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 3 countries.
Funding
Abstract
rationaleOxidized palmitoyl arachidonyl phosphatidylcholine (Ox-PAPC) accumulates in atherosclerotic lesions, is proatherogenic, and influences the expression of more than 1000 genes in endothelial cells.
objectiveTo elucidate the major pathways involved in Ox-PAPC action, we conducted a systems analysis of endothelial cell gene expression after exposure to Ox-PAPC. METHODS AND
resultsWe used the variable responses of primary endothelial cells from 149 individuals exposed to Ox-PAPC to construct a network that consisted of 11 groups of genes, or modules. Modules were enriched for a broad range of Gene Ontology pathways, some of which have not been identified previously as major Ox-PAPC targets. Further validating our method of network construction, modules were consistent with relationships established by cell biology studies of Ox-PAPC effects on endothelial cells. This network provides novel hypotheses about molecular interactions, as well as candidate molecular regulators of inflammation and atherosclerosis. We validated several hypotheses based on network connections and genomic association. Our network analysis predicted that the hub gene CHAC1 (cation transport regulator homolog 1) was regulated by the ATF4 (activating transcription factor 4) arm of the unfolded protein response pathway, and here we showed that ATF4 directly activates an element in the CHAC1 promoter. We showed that variation in basal levels of heme oxygenase 1 (HMOX1) contribute to the response to Ox-PAPC, consistent with its position as a hub in our network. We also identified G-protein-coupled receptor 39 (GPR39) as a regulator of HMOX1 levels and showed that it modulates the promoter activity of HMOX1. We further showed that OKL38/OSGN1 (oxidative stress-induced growth inhibitor), the hub gene in the blue module, is a key regulator of both inflammatory and antiinflammatory molecules.
conclusionsOur systems genetics approach has provided a broad view of the pathways involved in the response of endothelial cells to Ox-PAPC and also identified novel regulatory mechanisms.
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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.