ArticlePloS one2016
Histone Methyltransferase Enhancer of Zeste Homolog 2-Mediated ABCA1 Promoter DNA Methylation Contributes to the Progression of Atherosclerosis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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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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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- Polycomb Repressive Complex 2 drives flow-sensitive endothelial states underlying vascular inflammation and disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Epigenetic regulation in atherosclerosis and its therapeutic potential.Nature reviews. Cardiology · 2026Review
- The Complex Role of Methylation in Regulating Vascular Smooth Muscle Cell Phenotypic States in Vascular Remodeling and Atherosclerosis.Biomolecules · 2026Review
- Crosstalk between lipid metabolism and epigenetics in cellular senescence and age-related diseases.npj aging · 2026Review
- Roles of different methylation modifications in cardiovascular disease.Frontiers of medicine · 2025Review
- Epigenetic‑ncRNA crosstalk in atherosclerosis: Mechanisms, disease progression and therapeutic potential (Review).International journal of molecular medicine · 2025Review
- Article
- Roles and mechanisms of histone methylation in vascular aging and related diseases.Clinical epigenetics · 2025Review
- Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2.Nature communications · 2025Article
- Epigenetic regulation in coronary artery disease: from mechanisms to emerging therapies.Frontiers in molecular biosciences · 2025Review
- Repressive H3K27me3 drives hyperglycemia-induced oxidative and inflammatory transcriptional programs in human endothelium.Cardiovascular diabetology · 2024Article
- Lactate metabolism and lactylation in cardiovascular disease: novel mechanisms and therapeutic targets.Frontiers in cardiovascular medicine · 2024Review
- DNA methylation and histone post-translational modifications in atherosclerosis and a novel perspective for epigenetic therapy.Cell communication and signaling : CCS · 2023Review
- Myeloid BAF60a deficiency alters metabolic homeostasis and exacerbates atherosclerosis.Cell reports · 2023Article
- Review
- Epigenetic Regulation of Macrophage Polarization in Cardiovascular Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Epigenetic modifications as therapeutic targets in atherosclerosis: a focus on DNA methylation and non-coding RNAs.Frontiers in cardiovascular medicine · 2023Review
- Endothelial-to-mesenchymal transition: An underappreciated mediator of diabetic complications.Frontiers in endocrinology · 2023Review
- Molecular mechanisms for ABCA1-mediated cholesterol efflux.Cell cycle (Georgetown, Tex.) · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATP-binding cassette transporter A1 (ABCA1) plays a critical role in maintaining cellular cholesterol homeostasis. The purpose of this study is to identify the molecular mechanism(s) underlying ABCA1 epigenetic modification and determine its potential impact on ABCA1 expression in macrophage-derived foam cell formation and atherosclerosis development. DNA methylation induced foam cell formation from macrophages and promoted atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Bioinformatics analyses revealed a large CpG island (CGI) located in the promoter region of ABCA1. Histone methyltransferase enhancer of zeste homolog 2 (EZH2) downregulated ABCA1 mRNA and protein expression in THP-1 and RAW264.7 macrophage-derived foam cells. Pharmacological inhibition of DNA methyltransferase 1 (DNMT1) with 5-Aza-dC or knockdown of DNMT1 prevented the downregulation of macrophage ABCA1 expression, suggesting a role of DNA methylation in ABCA1 expression. Polycomb protein EZH2 induced DNMT1 expression and methyl-CpG-binding protein-2 (MeCP2) recruitment, and stimulated the binding of DNMT1 and MeCP2 to ABCA1 promoter, thereby promoting ABCA1 gene DNA methylation and atherosclerosis. Knockdown of DNMT1 inhibited EZH2-induced downregulation of ABCA1 in macrophages. Conversely, EZH2 overexpression stimulated DNMT1-induced ABCA1 gene promoter methylation and atherosclerosis. EZH2-induced downregulation of ABCA1 gene expression promotes foam cell formation and the development of atherosclerosis by DNA methylation of ABCA1 gene promoter.
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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.