ArticleScientific reports2017
The Mammalian Target of Rapamycin and DNA methyltransferase 1 axis mediates vascular endothelial dysfunction in response to disturbed flow.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Mechanometabolic endothelial senescence as a translational framework for cardiometabolic vascular disease and vascular ageing.Molecular biology reports · 2026Review
- Metabolic Overdrive in Elite Sport: A Systems Model of AMPK-mTOR Oscillation, NADInternational journal of molecular sciences · 2026Review
- Metaboloepigenetics: Role in the Regulation of Flow-Mediated Endothelial (Dys)Function and Atherosclerosis.Cells · 2025Review
- Vascular mechanotransduction.Physiological reviews · 2023Review
- DNMT1 mediates the disturbed flow-induced endothelial to mesenchymal transition through disrupting β-alanine and carnosine homeostasis.Theranostics · 2023Article
- G Protein-Coupled Receptor 37L1 Modulates Epigenetic Changes in Human Renal Proximal Tubule Cells.International journal of molecular sciences · 2022Article
- Geometric Constraints Regulate Energy Metabolism and Cellular Contractility in Vascular Smooth Muscle Cells by Coordinating Mitochondrial DNA Methylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Blood Reflux-Induced Epigenetic Factors HDACs and DNMTs Are Associated with the Development of Human Chronic Venous Disease.International journal of molecular sciences · 2022Article
- Theories and Molecular Basis of Vascular Aging: A Review of the Literature from VascAgeNet Group on Pathophysiological Mechanisms of Vascular Aging.International journal of molecular sciences · 2022Review
- An Interplay between Epigenetics and Translation in Oocyte Maturation and Embryo Development: Assisted Reproduction Perspective.Biomedicines · 2022Review
- Targeting the epigenome in in-stent restenosis: from mechanisms to therapy.Molecular therapy. Nucleic acids · 2021Review
- Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment.Frontiers in pharmacology · 2021Review
- Roles and Mechanisms of DNA Methylation in Vascular Aging and Related Diseases.Frontiers in cell and developmental biology · 2021Review
- Hemodynamics mediated epigenetic regulators in the pathogenesis of vascular diseases.Molecular and cellular biochemistry · 2021Review
- The Key Role of DNA Methylation and Histone Acetylation in Epigenetics of Atherosclerosis.Journal of lipid and atherosclerosis · 2020Review
- Atherosclerosis and flow: roles of epigenetic modulation in vascular endothelium.Journal of biomedical science · 2019Review
- Molecular mechanisms and genetic regulation in atherosclerosis.International journal of cardiology. Heart & vasculature · 2018Review
- DNMT1, a Novel Regulator Mediating mTORC1/mTORC2 Pathway-Induced NGF Expression in Schwann Cells.Neurochemical research · 2018Article
- Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The earliest atherosclerotic lesions preferentially develop in arterial regions experienced disturbed blood flow, which induces endothelial expression of pro-atherogenic genes and the subsequent endothelial dysfunction. Our previous study has demonstrated an up-regulation of DNA methyltransferase 1 (DNMT1) and a global hypermethylation in vascular endothelium subjected to disturbed flow. Here, we determined that DNMT1-specific inhibition in arterial wall ameliorates the disturbed flow-induced atherosclerosis through, at least in part, targeting cell cycle regulator cyclin A and connective tissue growth factor (CTGF). We identified the signaling pathways mediating the flow-induction of DNMT1. Inhibition of the mammalian target of rapamycin (mTOR) suppressed the DNMT1 up-regulation both in vitro and in vivo. Together, our results demonstrate that disturbed flow influences endothelial function and induces atherosclerosis in an mTOR/DNMT1-dependent manner. The conclusions obtained from this study might facilitate further evaluation of the epigenetic regulation of endothelial function during the pathological development of atherosclerosis and offer novel prevention and therapeutic targets of this disease.
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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.