ArticleThe Journal of clinical investigation2014
Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 1 of them a synthesis that pooled it.
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Who cites it
192 citing papers in PubMed, 1 synthesis or guideline pooled it, 299 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- Nuclear mechanotransduction: tools for mechanical perturbation and chromatin characterization.Nucleus (Austin, Tex.) · 2026Review
- Polycystin-1 suppresses apoptotic signalling in endothelial cells and protects from atherosclerosis.Cardiovascular research · 2026Article
- Mechanometabolic endothelial senescence as a translational framework for cardiometabolic vascular disease and vascular ageing.Molecular biology reports · 2026Review
- DNA/RNA Methylation-Driven Coronary Microvascular Dysfunction: Emerging Pathogenic Mechanisms and Therapeutic Opportunities for Heart Failure in Diabetes.Cardiovascular drugs and therapy · 2026Review
- 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
- Diagnostic potential of circular RNAs in carotid atherosclerotic plaque vulnerability.Non-coding RNA research · 2026Article
- Immune Roles of Canonically Non-Immune Cells in Biomaterials Response.Cell biomaterials · 2026Article
- Unraveling Atherosclerosis through Multi-omics: Systematic Insights into the Unique Applications and Clinical Perspectives.Current atherosclerosis reports · 2026Review
- Purine metabolic adaptation protects the endothelium from disturbed flow-induced DNA damage and atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- DNA Methylation: A Key Epigenetic Regulator of Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- Metabolic-epigenetic axis in cardiovascular inflammatory injury: regulatory mechanisms and intervention strategies.Frontiers in cardiovascular medicine · 2026Review
- Disturbed flow induces reprogramming of endothelial cells to immune-like and foam cells under hypercholesterolaemia during atherogenesis.Cardiovascular research · 2025Article
- DNA methylation signatures of Life's Essential 8 and their implications for dementia.Alzheimer's research & therapy · 2025Article
- Epigenetic‑ncRNA crosstalk in atherosclerosis: Mechanisms, disease progression and therapeutic potential (Review).International journal of molecular medicine · 2025Review
- Impacts of aging and fluid shear stress on vascular endothelial metabolism and atherosclerosis development.Journal of biomedical science · 2025Review
- Anti-ageing interventions for the treatment of cardiovascular disease.Cardiovascular research · 2025Review
- Upregulation of TLR-MYD88 signaling, stem cell genes, and Klotho mediates sepsis-associated myocardial inflammation.Molecular biology reports · 2025Article
- Chronic Disturbed Flow Induces Superficial Erosion-Prone Lesion via Endothelial-to-Mesenchymal Transition in a DNA Methyltransferase-Dependent Manner.Journal of atherosclerosis and thrombosis · 2025Article
132 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
In atherosclerosis, plaques preferentially develop in arterial regions of disturbed blood flow (d-flow), which alters endothelial gene expression and function. Here, we determined that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase-dependent (DNMT-dependent) manner. Induction of d-flow by partial carotid ligation surgery in a murine model induced DNMT1 in arterial endothelium. In cultured endothelial cells, DNMT1 was enhanced by oscillatory shear stress (OS), and reduction of DNMT with either the inhibitor 5-aza-2'-deoxycytidine (5Aza) or siRNA markedly reduced OS-induced endothelial inflammation. Moreover, administration of 5Aza reduced lesion formation in 2 mouse models of atherosclerosis. Using both reduced representation bisulfite sequencing (RRBS) and microarray, we determined that d-flow in the carotid artery resulted in hypermethylation within the promoters of 11 mechanosensitive genes and that 5Aza treatment restored normal methylation patterns. Of the identified genes, HoxA5 and Klf3 encode transcription factors that contain cAMP response elements, suggesting that the methylation status of these loci could serve as a mechanosensitive master switch in gene expression. Together, our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.
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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.