ArticlePhysiological genomics2014
Differential regulation of DNA methylation versus histone acetylation in cardiomyocytes during HHcy in vitro and in vivo: an epigenetic mechanism.
Article in Physiological genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- ETS‑1/ETS‑2 transcription factors in CVD (Review).International journal of molecular medicine · 2026Review
- Role and research progress of histone modification in cardiovascular diseases (Review).Experimental and therapeutic medicine · 2025Review
- New Types of Post-Translational Modification of Proteins in Cardiovascular Diseases.Journal of cardiovascular translational research · 2025Review
- Epigenetics in Heart Failure.International journal of molecular sciences · 2024Review
- [High homocysteine level promotes autophagy and apoptosis of mouse hippocampal HT22 cells through the Notch1/Hes1 signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Targeting Homocysteine and Hydrogen Sulfide Balance as Future Therapeutics in Cancer Treatment.Antioxidants (Basel, Switzerland) · 2023Review
- Homocysteine as a Predictor of Paroxysmal Atrial Fibrillation-Related Events: A Scoping Review of the Literature.Diagnostics (Basel, Switzerland) · 2022Article
- The cardioprotective effects of the new crystal form of puerarin in isoproterenol-induced myocardial ischemia rats based on metabolomics.Scientific reports · 2020Article
- Association of Homocysteine, Methionine, and MTHFR 677C>T Polymorphism With Rate of Cardiovascular Multimorbidity Development in Older Adults in Sweden.JAMA network open · 2020Article
- Dysbiotic 1-carbon metabolism in cardiac muscle remodeling.Journal of cellular physiology · 2020Article
- Epigenetics, 1-Carbon Metabolism, and Homocysteine During Dysbiosis.Frontiers in physiology · 2020Article
- Overexpression of microRNA-203 can downregulate survivin and function as a potential therapeutic target in papillary thyroid cancer.Oncology letters · 2020Article
- Dysregulation of Epigenetic Mechanisms of Gene Expression in the Pathologies of Hyperhomocysteinemia.International journal of molecular sciences · 2019Review
- [Interactive regulatory effect of histone H3K9ac acetylation and histone H3K9me3 methylation on cardiomyogenesis in mice].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Article
- Hydrogen sulfide alleviates hyperhomocysteinemia-mediated skeletal muscle atrophy via mitigation of oxidative and endoplasmic reticulum stress injury.American journal of physiology. Cell physiology · 2018Article
- Cell‑specific histone modifications in atherosclerosis (Review).Molecular medicine reports · 2018Review
- High glucose induces podocyte epithelial‑to‑mesenchymal transition by demethylation‑mediated enhancement of MMP9 expression.Molecular medicine reports · 2018Article
- Epigenetic modifications in hyperhomocysteinemia: potential role in diabetic retinopathy and age-related macular degeneration.Oncotarget · 2018Article
- Histone 3 modifications and blood pressure in the Beijing Truck Driver Air Pollution Study.Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals · 2017Article
- Hypermethylation: Causes and Consequences in Skeletal Muscle Myopathy.Journal of cellular biochemistry · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The mechanisms of homocysteine-mediated cardiac threats are poorly understood. Homocysteine, being the precursor to S-adenosyl methionine (a methyl donor) through methionine, is indirectly involved in methylation phenomena for DNA, RNA, and protein. We reported previously that cardiac-specific deletion of N-methyl-d-aspartate receptor-1 (NMDAR1) ameliorates homocysteine-posed cardiac threats, and in this study, we aim to explore the role of NMDAR1 in epigenetic mechanisms of heart failure, using cardiomyocytes during hyperhomocysteinemia (HHcy). High homocysteine levels activate NMDAR1, which consequently leads to abnormal DNA methylation vs. histone acetylation through modulation of DNA methyltransferase 1 (DNMT1), HDAC1, miRNAs, and MMP9 in cardiomyocytes. HL-1 cardiomyocytes cultured in Claycomb media were treated with 100 μM homocysteine in a dose-dependent manner. NMDAR1 antagonist (MK801) was added in the absence and presence of homocysteine at 10 μM in a dose-dependent manner. The expression of DNMT1, histone deacetylase 1 (HDAC1), NMDAR1, microRNA (miR)-133a, and miR-499 was assessed by real-time PCR as well as Western blotting. Methylation and acetylation levels were determined by checking 5'-methylcytosine DNA methylation and chromatin immunoprecipitation. Hyperhomocysteinemic mouse models (CBS+/-) were used to confirm the results in vivo. In HHcy, the expression of NMDAR1, DNMT1, and matrix metalloproteinase 9 increased with increase in H3K9 acetylation, while HDAC1, miR-133a, and miR-499 decreased in cardiomyocytes. Similar results were obtained in heart tissue of CBS+/- mouse. High homocysteine levels instigate cardiovascular remodeling through NMDAR1, miR-133a, miR-499, and DNMT1. A decrease in HDAC1 and an increase in H3K9 acetylation and DNA methylation are suggestive of chromatin remodeling in HHcy.
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