ArticleRedox biology2020
DNA hypermethylation: A novel mechanism of CREG gene suppression and atherosclerogenic endothelial dysfunction.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Unraveling Atherosclerosis through Multi-omics: Systematic Insights into the Unique Applications and Clinical Perspectives.Current atherosclerosis reports · 2026Review
- Glucolipid Metabolic Disorders andInternational journal of endocrinology · 2026Review
- Proteomic analysis identifies lipoprotein(a)-associated proteins linked to incident atherosclerotic cardiovascular disease events.medRxiv : the preprint server for health sciences · 2025Article
- Luteolin Inhibits Ferroptosis of HUVEC by Regulating the Sirt1/Nrf2 Pathway.Cell biochemistry and biophysics · 2025Article
- Epigenetic‑ncRNA crosstalk in atherosclerosis: Mechanisms, disease progression and therapeutic potential (Review).International journal of molecular medicine · 2025Review
- Review
- LncRNA MEG3 independently collaborates with lncRNA TUG1 to prevent cholesterol efflux in ox-LDL-induced human umbilical vein endothelial cells.Molecular biology reports · 2025Article
- Unraveling the metabolic‒epigenetic nexus: a new frontier in cardiovascular disease treatment.Cell death & disease · 2025Review
- Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.Bone research · 2025Review
- The Impact of Modifiable Risk Factors on the Endothelial Cell Methylome and Cardiovascular Disease Development.Frontiers in bioscience (Landmark edition) · 2025Review
- Downregulation of FcRn promotes ferroptosis in herpes simplex virus-1-induced lung injury.Cellular and molecular life sciences : CMLS · 2025Article
- Epigenetic regulation in coronary artery disease: from mechanisms to emerging therapies.Frontiers in molecular biosciences · 2025Review
- CREG1 attenuates doxorubicin-induced cardiotoxicity by inhibiting the ferroptosis of cardiomyocytes.Redox biology · 2024Article
- CREG1 deficiency impaired myoblast differentiation and skeletal muscle regeneration.Journal of cachexia, sarcopenia and muscle · 2024Article
- 5-Aza-2'-Deoxycytidine Ameliorates Choroidal Neovascularization by Inhibiting the Wnt/β-Catenin Signaling Pathway.Investigative ophthalmology & visual science · 2024Article
- Analysis of global DNA methylation and epigenetic modifiers (DNMTs and HDACs) in human foetal endothelium exposed to gestational and type 2 diabetes.Epigenetics · 2023Article
- DNA methylation and histone post-translational modifications in atherosclerosis and a novel perspective for epigenetic therapy.Cell communication and signaling : CCS · 2023Review
- The CREG1-FBXO27-LAMP2 axis alleviates diabetic cardiomyopathy by promoting autophagy in cardiomyocytes.Experimental & molecular medicine · 2023Article
- RETRACTED: TRIM10 Is Downregulated in Acute Myeloid Leukemia and Plays a Tumor Suppressive Role via Regulating NF-κB Pathway.Cancers · 2023Article
- DNA methylation alternation in Stanford- A acute aortic dissection.BMC cardiovascular disorders · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveCellular repressor of E1A-stimulated genes (CREG), a vasculoprotective molecule, is significantly downregulated in atherosclerotic vessels through unclear mechanisms. While epigenetic regulation is involved in atherosclerosis development, it is not known if the CREG gene is epigenetically regulated. The aim of this study was to assess the potential role of CREG methylation in contributing to atherosclerosis. APPROACH AND
resultsOverexpression of DNA methyltransferase (DNMT)3B significantly inhibited CREG expression in human umbilical vein endothelial cells (HUVECs) and human coronary aortic endothelial cells (HCAECs).Conversely, inhibition of DNA methylation with 5-aza-2'-deoxycytidine (5-aza-dC) dose-dependently increased CREG expression. A CREG promoter analysis identified +168 to +255 bp as a key regulatory region and the CG site at +201/+202 bp as a key methylation site. The transcription factor GR-α could bind to the +201/+202 bp CG site promoting CREG transcription, a process significantly inhibited by DNMT3B overexpression. Treatment of cells with oxidized low-density lipoprotein (ox-LDL), a critical atherosclerogenic factor, significantly increased DNMT3B expression, increasing CREG promotor methylation, blocking GR-α binding, and inhibiting CREG expression. Consistently, CG sites in the CREG promoter fragment were hyper-methylated in human atherosclerotic arteries, and CREG expression was significantly reduced. A negative correlation between DNMT3B and CREG expression levels was observed in human atherosclerotic arteries. Finally, Ox-LDL-induced endothelium dysfunction was significantly attenuated by both 5-aza-dC and an anti-oxidative molecular N-acetylcysteine (NAC) administration through rescue the expression of CREG and activation of the p-eNOS/NO pathway.
conclusionsOur study provides the first direct evidence that DNMT3B-mediated CREG gene hypermethylation is a novel mechanism that contributes to endothelial dysfunction and atherosclerosis development. Blocking CREG methylation may represent a novel therapeutic approach to treat ox-LDL-induced atherosclerosis.
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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.