ArticleCardiovascular diabetology2023
Targeting high glucose-induced epigenetic modifications at cardiac level: the role of SGLT2 and SGLT2 inhibitors.
Article in Cardiovascular diabetology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Timing-dependent anti-inflammatory effects of empagliflozin in monocyte-derived macrophages from post-myocardial infarct patients with type 2 diabetes.Cardiovascular diabetology · 2026Trial
- Metabo-epigenetic circuits of heart failure: chromatin-modifying enzymes as determinants of metabolic plasticity.EMBO molecular medicine · 2026Review
- 4-Methylcatechol attenuates diabetic myocardial disorder via the ESR1-PI3K-AKT pathway.Frontiers in pharmacology · 2026Article
- Modern antidiabetic therapy by sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors against cardiovascular diseases.Pharmacological reviews · 2025Review
- SGLT2 Inhibitors: From Molecular Mechanisms to Clinical Outcomes in Cardiology and Diabetology.Molecules (Basel, Switzerland) · 2025Review
- Sodium-Glucose Cotransporter 2 Inhibitors in Aortic Stenosis: Toward a Comprehensive Cardiometabolic Approach.International journal of molecular sciences · 2025Review
- Cardiometabolic disease management: influences from epigenetics.Epigenomics · 2025Review
- Drug Discovery and Development for Heart Failure Using Multi-Omics Approaches.International journal of molecular sciences · 2025Review
- SGLT2 inhibitors: how do they affect the cardiac cells.Molecular and cellular biochemistry · 2025Review
- Integrated multiomic analyses: An approach to improve understanding of diabetic kidney disease.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Unfolding the complexity of epigenetics in male reproductive aging: a review of therapeutic implications.Molecular biology reports · 2024Review
- Empagliflozin protects against heart failure with preserved ejection fraction partly by inhibiting the senescence-associated STAT1-STING axis.Cardiovascular diabetology · 2024Article
- Co-localization of the sodium-glucose co-transporter-2 channel (SGLT-2) with endothelin ETA and ETB receptors in human cardiorenal tissue.Bioscience reports · 2024Article
- Challenges and opportunities in the management of type 2 diabetes in patients with lower extremity peripheral artery disease: a tailored diagnosis and treatment review.Cardiovascular diabetology · 2024Review
- New Molecules in Type 2 Diabetes: Advancements, Challenges and Future Directions.International journal of molecular sciences · 2024Review
- Narrative Review of Immunomodulatory and Anti-inflammatory Effects of Sodium-Glucose Cotransporter 2 Inhibitors: Unveiling Novel Therapeutic Frontiers.Kidney international reports · 2024Review
- Using Omics to Identify Novel Therapeutic Targets in Heart Failure.Circulation. Genomic and precision medicine · 2024Review
- The Cardioprotective and Anticancer Effects of SGLT2 Inhibitors:JACC. CardioOncology · 2024Review
- GLP-1 receptor agonists-SGLT-2 inhibitors combination therapy and cardiovascular events after acute myocardial infarction: an observational study in patients with type 2 diabetes.Cardiovascular diabetology · 2024Observational
- Recent Updates on Epigenetic-Based Pharmacotherapy for Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSodium-glucose co-transporters (SGLT) inhibitors (SGLT2i) showed many beneficial effects at the cardiovascular level. Several mechanisms of action have been identified. However, no data on their capability to act via epigenetic mechanisms were reported. Therefore, this study aimed to investigate the ability of SGLT2 inhibitors (SGLT2i) to induce protective effects at the cardiovascular level by acting on DNA methylation.
methodsTo better clarify this issue, the effects of empagliflozin (EMPA) on hyperglycemia-induced epigenetic modifications were evaluated in human ventricular cardiac myoblasts AC16 exposed to hyperglycemia for 7 days. Therefore, the effects of EMPA on DNA methylation of NF-κB, SOD2, and IL-6 genes in AC16 exposed to high glucose were analyzed by pyrosequencing-based methylation analysis. Modifications of gene expression and DNA methylation of NF-κB and SOD2 were confirmed in response to a transient SGLT2 gene silencing in the same cellular model. Moreover, chromatin immunoprecipitation followed by quantitative PCR was performed to evaluate the occupancy of TET2 across the investigated regions of NF-κB and SOD2 promoters.
resultsSeven days of high glucose treatment induced significant demethylation in the promoter regions of NF-kB and SOD2 with a consequent high level in mRNA expression of both genes. The observed DNA demethylation was mediated by increased TET2 expression and binding to the CpGs island in the promoter regions of analyzed genes. Indeed, EMPA prevented the HG-induced demethylation changes by reducing TET2 binding to the investigated promoter region and counteracted the altered gene expression. The transient SGLT2 gene silencing prevented the DNA demethylation observed in promoter regions, thus suggesting a role of SGLT2 as a potential target of the anti-inflammatory and antioxidant effect of EMPA in cardiomyocytes.
conclusionsIn conclusion, our results demonstrated that EMPA, mainly acting on SGLT2, prevented DNA methylation changes induced by high glucose and provided evidence of a new mechanism by which SGLT2i can exert cardio-beneficial effects.
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