ArticleExperimental cell research2021
The human aortic endothelium undergoes dose-dependent DNA methylation in response to transient hyperglycemia.
Article in Experimental cell research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review.Frontiers in endocrinology · 2021Pooled it
- Transient elevation in cellular glucose uptake exacerbates pressure overload-induced cardiac hypertrophy and dysfunction.Epigenetics · 2026Article
- DNA/RNA Methylation-Driven Coronary Microvascular Dysfunction: Emerging Pathogenic Mechanisms and Therapeutic Opportunities for Heart Failure in Diabetes.Cardiovascular drugs and therapy · 2026Review
- Epigenetic dysregulation in osteonecrosis of the femoral head: a critical review of DNA methylation, histone modifications, and clinical translation.Journal of orthopaedic surgery and research · 2026Review
- Circular RNAs and endothelial dysfunction: mechanistic crosstalk and emerging therapeutic perspectives.Cellular and molecular life sciences : CMLS · 2025Review
- Established and Emerging Roles of Epigenetic Regulation in Diabetic Cardiomyopathy.Diabetes/metabolism research and reviews · 2025Review
- TET2 has endothelial-specific roles in interferon responses that are dysregulated by hyperglycemia in vitro and in vivo.The Journal of biological chemistry · 2025Article
- Mechanisms of Impaired Wound Healing in Type 2 Diabetes: The Role of Epigenetic Factors.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Tissue nanotransfection-based endothelial PLCγ2-targeted epigenetic gene editing rescues perfusion and diabetic ischemic wound healing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The Impact of Modifiable Risk Factors on the Endothelial Cell Methylome and Cardiovascular Disease Development.Frontiers in bioscience (Landmark edition) · 2025Review
- Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis.Clinical epigenetics · 2025Article
- The functional significance of vascular DNA hypermethylation in atherosclerosis: a historical perspective.Frontiers in pharmacology · 2025Review
- Analysis of global DNA methylation and epigenetic modifiers (DNMTs and HDACs) in human foetal endothelium exposed to gestational and type 2 diabetes.Epigenetics · 2023Article
- Genes, environment, and African ancestry in cardiometabolic disorders.Trends in endocrinology and metabolism: TEM · 2023Review
- Bibliometric and visual analysis of RAN methylation in cardiovascular disease.Frontiers in cardiovascular medicine · 2023Article
- Recent advances in molecular biology of metabolic syndrome pathophysiology: endothelial dysfunction as a potential therapeutic target.Journal of diabetes and metabolic disorders · 2022Review
- Promising Strategies for Preserving Adult Endothelium Health and Reversing Its Dysfunction: From Liquid Biopsy to New Omics Technologies and Noninvasive Circulating Biomarkers.International journal of molecular sciences · 2022Review
- Systems biology of angiogenesis signaling: Computational models and omics.WIREs mechanisms of disease · 2022Review
- Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus 2.0.International journal of molecular sciences · 2022Review
- Clinical epigenetics and restoring of metabolic health in severely obese patients undergoing batriatric and metabolic surgery.Updates in surgery · 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
9 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundGlycemic control is a strong predictor of long-term cardiovascular risk in patients with diabetes mellitus, and poor glycemic control influences long-term risk of cardiovascular disease even decades after optimal medical management. This phenomenon, termed glycemic memory, has been proposed to occur due to stable programs of cardiac and endothelial cell gene expression. This transcriptional remodeling has been shown to occur in the vascular endothelium through a yet undefined mechanism of cellular reprogramming.
methodsIn the current study, we quantified genome-wide DNA methylation of cultured human endothelial aortic cells (HAECs) via reduced-representation bisulfite sequencing (RRBS) following exposure to diabetic (250 mg/dL), pre-diabetic (125 mg/dL), or euglycemic (100 mg/dL) glucose concentrations for 72 h (n = 2).
resultsWe discovered glucose-dependent methylation of genomic regions (DMRs) encompassing 2199 genes, with a disproportionate number found among genes associated with angiogenesis and nitric oxide (NO) signaling-related pathways. Multi-omics analysis revealed differential methylation and gene expression of VEGF (↑5.6% DMR, ↑3.6-fold expression), and NOS3 (↓20.3% DMR, ↓1.6-fold expression), nodal regulators of angiogenesis and NO signaling, respectively.
conclusionIn the current exploratory study, we examine glucose-dependent and dose-responsive alterations in endothelial DNA methylation to examine a putative epigenetic mechanism underlying diabetic vasculopathy. Specifically, we uncover the disproportionate glucose-dependent methylation and gene expression of VEGF and NO signaling cascades, a physiologic imbalance known to cause endothelial dysfunction in diabetes. We therefore hypothesize that epigenetic mechanisms encode a glycemic memory within endothelial cells.
Indexed as
Identifiers
What OpenQuestion holds
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.