ArticleBlood2007
Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin A gene.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Identification of methylation-regulated genes modulating microglial phagocytosis in hyperhomocysteinemia-exacerbated Alzheimer's disease.Alzheimer's research & therapy · 2023Pooled it
- Abnormal Hypermethylation at Imprinting Control Regions in Patients with S-Adenosylhomocysteine Hydrolase (AHCY) Deficiency.PloS one · 2016Trial
- One-carbon metabolism and cardiovascular disease: Molecular mechanisms, genetic influences, and epigenetic regulation.Biochemistry and biophysics reports · 2026Review
- SHMT2 deficiency disrupts transcriptional regulation through homocysteine-mediated suppression of histone lactylation in Huntington's disease models.The Journal of clinical investigation · 2026Article
- Review
- The Impact of Modifiable Risk Factors on the Endothelial Cell Methylome and Cardiovascular Disease Development.Frontiers in bioscience (Landmark edition) · 2025Review
- Epigenetic modifications in abdominal aortic aneurysms: from basic to clinical.Frontiers in cardiovascular medicine · 2024Review
- Early hyperlipidemia triggers metabolomic reprogramming with increased SAH, increased acetyl-CoA-cholesterol synthesis, and decreased glycolysis.Redox biology · 2023Article
- Review
- Cigarette Smoke Modulates Inflammation and ImmunityAntioxidants & redox signaling · 2023Review
- Homocysteine-Potential Novel Diagnostic Indicator of Health and Disease in Horses.Animals : an open access journal from MDPI · 2023Review
- Editorial: Insights in cardiovascular therapeutics 2022-cardiovascular innate immunity.Frontiers in cardiovascular medicine · 2023Article
- Elevated homocysteine level as an indicator for chronic kidney disease in community-dwelling middle-aged and elderly populations in Taiwan: A community-based cross-sectional study.Frontiers in medicine · 2022Article
- Molecular processes mediating hyperhomocysteinemia-induced metabolic reprogramming, redox regulation and growth inhibition in endothelial cells.Redox biology · 2021Article
- Endothelial Dysfunction and Hyperhomocysteinemia-Linked Cerebral Small Vessel Disease: Underlying Mechanisms and Treatment Timing.Frontiers in neurology · 2021Review
- Novel Knowledge-Based Transcriptomic Profiling of Lipid Lysophosphatidylinositol-Induced Endothelial Cell Activation.Frontiers in cardiovascular medicine · 2021Article
- Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD.Journal of immunology research · 2021Article
- The association between total homocysteine and blood pressure in two independent Chinese populations.Journal of human hypertension · 2020Article
- Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management.Cellular and molecular life sciences : CMLS · 2020Review
- Homocysteine-methionine cycle is a metabolic sensor system controlling methylation-regulated pathological signaling.Redox biology · 2020Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
We reported previously that homocysteine (Hcy) inhibits endothelial cell (EC) growth by transcriptional inhibition of the cyclin A gene via a hypomethylation-related mechanism. In this study, we examined the effect of Hcy on epigenetic modification of the cyclin A gene and its biologic role in human ECs. Cyclin A mRNA levels were significantly suppressed by Hcy and a DNA methyltransferase inhibitor. The cyclin A promoter contains a CpG island spanning a 477-bp region (-277/200). Bisulfite sequencing followed by polymerase chain reaction (PCR) amplification of the cyclin A promoter (-267/37) showed that Hcy eliminated methylation at 2 CpG sites in the cyclin A promoter, one of which is located on the cycle-dependent element (CDE). Mutation of CG sequence on the CDE leads to a 6-fold increase in promoter activity. Hcy inhibited DNA methyltransferase 1 (DNMT1) activity by 30%, and reduced the binding of methyl CpG binding protein 2 (MeCP2) and increased the bindings of acetylated histone H3 and H4 in the cyclin A promoter. Finally, adenovirus-transduced DNMT1 gene expression reversed the inhibitory effect of Hcy on cyclin A expression and EC growth inhibition. In conclusion, Hcy inhibits cyclin A transcription and cell growth by inhibiting DNA methylation through suppression of DNMT1 in ECs.
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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.