Targeting high glucose-induced epigenetic modifications at cardiac level: the role of SGLT2 and SGLT2 inhibitors

Article Endocrinology & Metabolism

Sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiac function by reducing JunD expression in human diabetic hearts

Raffaele Marfella et al.

Summary: The early pathogenesis of human diabetic cardiomyopathy is associated with overexpression of JunD/PPAR-gamma and lipid accumulation, which can be attenuated by treatment with SGLT2 inhibitors in diabetic patients.

METABOLISM-CLINICAL AND EXPERIMENTAL (2022)

Add to Collection

Article Biochemistry & Molecular Biology

Dapagliflozin Protects H9c2 Cells Against Injury Induced by Lipopolysaccharide via Suppression of CX3CL1/CX3CR1 Axis and NF-κB Activity

Yousef Faridvand et al.

Summary: The current study demonstrates that dapagliflozin ameliorates inflammation and oxidative stress in LPS-treated H9c2 cells by reducing the levels of MDA, ROS, and TNF-α. Additionally, dapagliflozin reduces the expression of CX3CL1/CX3CR1 and attenuates NF-kappa B p65 DNA binding activity, thus alleviating LPS-induced injury in H9c2 cells.

CURRENT MOLECULAR PHARMACOLOGY (2022)

Add to Collection

Article Cardiac & Cardiovascular Systems

Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry

Pasquale Paolisso et al.

Summary: The study found that type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents.

CARDIOVASCULAR DIABETOLOGY (2022)

Add to Collection

Review Cardiac & Cardiovascular Systems

Direct cardiac effects of SGLT2 inhibitors

Sha Chen et al.

Summary: SGLT2 inhibitors have direct effects on cardiac cells, affecting ion balance, reducing inflammation and oxidative stress, regulating metabolism, and improving cardiac function. The unified explanation for these effects is the inhibition of sodium-loaders that affect the heart, especially under pathological conditions.

CARDIOVASCULAR DIABETOLOGY (2022)

Add to Collection

Article Pharmacology & Pharmacy

Dapagliflozin exerts anti-inflammatory effects via inhibition of LPS-induced TLR-4 overexpression and NF-κB activation in human endothelial cells and differentiated macrophages

Elaheh Abdollahi et al.

Summary: Evidence suggests that the new class of anti-diabetic drugs, SGLT2 inhibitors, can have beneficial effects on atherosclerotic complications of diabetes. This study aimed to evaluate the direct anti-inflammatory effects of the SGLT2 inhibitor dapagliflozin (DAPA). The results showed that DAPA could attenuate inflammation by inhibiting the expression of TLR-4 and activation of NF-kappa B, as well as shifting macrophage polarization from an inflammatory state to an anti-inflammatory state.

EUROPEAN JOURNAL OF PHARMACOLOGY (2022)

Add to Collection

Article Biochemistry & Molecular Biology

Sodium Glucose Cotransporter-2 Inhibitors: Spotlight on Favorable Effects on Clinical Outcomes beyond Diabetes

Vera Certikova Chabova et al.

Summary: SGLT2 inhibitors have beneficial effects not only in improving diabetes compensation, but also in kidney and cardiovascular outcomes. These benefits are not limited to diabetics, but also found in non-diabetic individuals. The pathophysiological pathways underlying the treatment success have been investigated in clinical and experimental studies.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Add to Collection

Review Biochemistry & Molecular Biology

Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis

Irina Bure et al.

Summary: In recent years, scientists have increasingly suggested and confirmed that epigenetic regulators are closely linked and form a comprehensive network of regulatory pathways and feedback loops. This is particularly important for a better understanding of the development and progression of various diseases.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Add to Collection

Review Cardiac & Cardiovascular Systems

Cardiac mechanisms of the beneficial effects of SGLT2 inhibitors in heart failure: Evidence for potential off-target effects

Jason R. B. Dyck et al.

Summary: SGLT2 inhibitors have promising effects in treating heart failure patients. This review summarizes the cardiac effects of SGLT2i, including their impact on inflammation, oxidative stress, ion transport, and metabolism. These mechanisms play a crucial role in the development of heart failure.

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY (2022)

Add to Collection

Article Cardiac & Cardiovascular Systems

Guidelines for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes JACC Guideline Comparison

Michelle D. Kelsey et al.

Summary: Cardiovascular disease is a major concern for individuals with type 2 diabetes mellitus, and aggressive risk factor management is crucial for these high-risk patients. Recommendations and guidelines from professional societies in cardiology, endocrinology, nephrology, and general medicine in the United States and Europe provide guidance on cardiovascular risk reduction for patients with type 2 diabetes mellitus. While there are some differences in risk stratification, treatment targets for low-density lipoprotein-cholesterol and blood pressure, as well as the use of specific medications, overall there is significant alignment across recommendations from different professional societies.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2022)

Add to Collection

Review Pharmacology & Pharmacy

Emerging Roles of Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitors in Diabetic Cardiovascular Diseases: Focusing on Immunity, Inflammation and Metabolism

Lingxiang Xie et al.

Summary: Diabetes patients face increased cardiovascular risks and SGLT-2 inhibitors have potential cardiovascular protective effects, although their mechanisms of action are not fully understood. This review summarizes the multifactorial mechanisms of SGLT-2 inhibitors in regulating immunity, inflammation, and metabolism, and presents future directions for preventing or delaying cardiovascular complications in diabetes.

FRONTIERS IN PHARMACOLOGY (2022)

Add to Collection

Review Genetics & Heredity

The Role of Epigenetic Modifications in Late Complications in Type 1 Diabetes

Barbara Cugalj Kern et al.

Summary: Long-term hyperglycemia caused by type 1 diabetes has a significant impact on epigenetic marks in late complications, such as DNA methylation, histone modifications, and microRNAs.

GENES (2022)

Add to Collection

Article Biochemistry & Molecular Biology

Blocking of SGLT2 to Eliminate NADPH-Induced Oxidative Stress in Lenses of Animals with Fructose-Induced Diabetes Mellitus

Ying-Ying Chen et al.

Summary: Chronic hyperglycemia leads to oxidative stress in patients with diabetes, causing damage to their vision. This study found that dapagliflozin, metformin, and resveratrol can reduce oxidative stress. These findings suggest that blocking SGLT2 may be beneficial for improving cataracts in patients with diabetes.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Add to Collection

Article Pharmacology & Pharmacy

Characterization of the SGLT2 Interaction Network and Its Regulation by SGLT2 Inhibitors: A Bioinformatic Analysis

Zofia Wicik et al.

Summary: This study provides comprehensive and ranked information about the SGLT2 interaction network in the context of tissue expression and can help to predict the clinical effects of the SGLT2i.

FRONTIERS IN PHARMACOLOGY (2022)

Add to Collection

Article Pharmacology & Pharmacy

Sodium-glucose cotransporter-2 (SGLT2) expression in diabetic and non-diabetic failing human cardiomyocytes

Raffaele Marfella et al.

Summary: The study focused on investigating SGLT2 expression in human cardiomyocytes, revealing higher levels in diabetic patients compared to non-diabetic patients.

PHARMACOLOGICAL RESEARCH (2022)

Add to Collection

Review Cardiac & Cardiovascular Systems

Anti-inflammatory role of SGLT2 inhibitors as part of their anti-atherosclerotic activity: Data from basic science and clinical trials

Lucia Scisciola et al.

Summary: Atherosclerosis is an inflammatory disease that leads to cardiovascular mortality and morbidity. Type 2 diabetes mellitus is a known risk factor for atherosclerosis. Sodium-glucose co-transporter 2 inhibitors have been found to have anti-inflammatory effects and can potentially slow down the progression of atherosclerosis.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2022)

Add to Collection

Article Medicine, Research & Experimental

Effects of SGLT2 Inhibitors on Ion Homeostasis and Oxidative Stress associated Mechanisms in Heart Failure

Gloria M. Gager et al.

Summary: SGLT2 inhibitors have cardioprotective effects in patients with type 2 diabetes, with potential molecular targets including alterations in Ca2+ signaling, oxidative stress, and endothelial dysfunction.

BIOMEDICINE & PHARMACOTHERAPY (2021)

Add to Collection

Article Cardiac & Cardiovascular Systems

Diabetes status-related differences in risk factors and mediators of heart failure in the general population: results from the MORGAM/BiomarCaRE consortium

Matti A. Vuori et al.

Summary: The main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.

CARDIOVASCULAR DIABETOLOGY (2021)

Add to Collection

Article Cell Biology

New insight in molecular mechanisms regulating SIRT6 expression in diabetes: Hyperglycaemia effects on SIRT6 DNA methylation

Lucia Scisciola et al.

Summary: Conflicting data exist on the relationship between hyperglycaemia, diabetes, and SIRT6 expression. This study found that high glucose exposure led to lower DNA methylation in the SIRT6 promoter, increased expression of SIRT6 and TET2, and persisting epigenetic changes after glucose normalization. Diabetic patients had lower SIRT6 DNA methylation levels that correlated inversely with plasma glucose levels, indicating the involvement of epigenetic mechanisms in regulating SIRT6 expression.

JOURNAL OF CELLULAR PHYSIOLOGY (2021)

Add to Collection

Article Public, Environmental & Occupational Health

Trend analysis of cardiovascular disease mortality, incidence, and mortality-to-incidence ratio: results from global burden of disease study 2017

Maedeh Amini et al.

Summary: The study found a global upward trend in the incidence of cardiovascular diseases (CVDs) until 1996, followed by a downward trend. Nearly all countries experienced a significant decline in mortality rates from 1990 to 2017. Developed countries saw a faster reduction in incidence and mortality rates compared to developing countries, while the global MIR had a slight decrease with developing nations showing a more gradual decline.

BMC PUBLIC HEALTH (2021)

Add to Collection

Article Pharmacology & Pharmacy

Empagliflozin alleviates ethanol-induced cardiomyocyte injury through inhibition of mitochondrial apoptosis via a SIRT1/PTEN/Akt pathway

Ge Tian et al.

Summary: The study found that EMPA pretreatment can increase cell viability, decrease LDH activity, reduce cardiomyocyte apoptosis, decrease cleaved caspase 3 expression. Additionally, EMPA inhibits ethanol-induced mitochondrial apoptosis via the SIRT1/PTEN/Akt pathway.

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY (2021)

Add to Collection

Review Cardiac & Cardiovascular Systems

Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure

Shruti S. Joshi et al.

Summary: Patients with type 2 diabetes mellitus are at higher risk for heart failure, but SGLT2 inhibitor therapies show promise in improving blood glucose control and reducing cardiovascular events. However, the mechanisms underlying these benefits are not fully understood, with recent proposals pointing to improvements in cardiomyocyte calcium handling and reduction in epicardial fat as potential explanations.

HEART (2021)

Add to Collection

Review Pharmacology & Pharmacy

SGLT-2 inhibitors reduce the risk of cerebrovascular/cardiovascular outcomes and mortality: A systematic review and meta-analysis of retrospective cohort studies

Annamaria Mascolo et al.

Summary: This study conducted a meta-analysis to evaluate the effects of SGLT2 inhibitors on cardiovascular and cerebrovascular outcomes in patients with T2DM. The results showed that SGLT2 inhibitors reduced the risk of stroke compared to DPP-4 inhibitors and non-SGLT2 inhibitors, and were also associated with decreased risk of cardiovascular outcomes and mortality in all comparisons.

PHARMACOLOGICAL RESEARCH (2021)

Add to Collection

Article Endocrinology & Metabolism

Sodium-glucose co-transporter2 expression and inflammatory activity in diabetic atherosclerotic plaques: Effects of sodium-glucose co-transporter2 inhibitor treatment

Nunzia D'Onofrio et al.

Summary: The study demonstrated that SGLT2 inhibitors have a positive regulatory effect on atherosclerotic plaques in diabetic patients, showing significant improvements in inflammation and oxidative stress. Patients without diabetes had significantly higher overall survival from MACE at 2-year follow-up, while diabetic patients using SGLT2 inhibitors had a significantly lower rate of MACE over 2 years compared to non-users.

MOLECULAR METABOLISM (2021)

Add to Collection

Review Endocrinology & Metabolism

Therapeutic Targeting of SGLT2: A New Era in the Treatment of Diabetes and Diabetic Kidney Disease

James Shaffner et al.

Summary: SGLT2 inhibitors have shown significant renal protective effects and metabolic reprogramming in the treatment of DKD. Despite ongoing debates over their mechanisms of action and effectiveness, these inhibitors have been proven to be safe and beneficial for patients with GFR >= 30mL/min/1.73m(2).

FRONTIERS IN ENDOCRINOLOGY (2021)

Add to Collection

Review Cardiac & Cardiovascular Systems

Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey

Donato Cappetta et al.

Summary: Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases with common risk factors and underlying mechanisms; The cardiovascular benefits of SGLT2 inhibitors may be related to their cardiac-specific mechanisms; Research suggests that reducing intracellular sodium levels is a key mechanism for the direct cardiac effects of SGLT2 inhibitors.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2021)

Add to Collection

Article Cardiac & Cardiovascular Systems

Adiponectin Related Vascular and Cardiac Benefits in Obesity: Is There a Role for an Epigenetically Regulated Mechanism?

Rosaria Anna Fontanella et al.

Summary: The study confirmed the role of epigenetics in obesity-related cardiovascular complications, and proposed plasma miRNA-21 and IL-6 as well as NF-kB DNA methylation changes in nucleated blood cells as potential biomarkers for evaluating cardiovascular risk in obesity. It also showed the protective role of adiponectin in preventing epigenetic modifications induced by increased adipose tissue content in obese individuals. Further research is needed to explore the exact mechanisms of obesity-related epigenetic modifications in blood cells and their reflection of changes in adipose and myocardial tissues.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2021)

Add to Collection

Article Pharmacology & Pharmacy

Sodium-Glucose CoTransporter-2 Inhibitor Empagliflozin Ameliorates Sunitinib-Induced Cardiac Dysfunction via Regulation of AMPK-mTOR Signaling Pathway-Mediated Autophagy

Changzhen Ren et al.

Summary: In a mouse model, the SGLT2 inhibitor empagliflozin was found to protect against sunitinib-induced cardiac dysfunction by regulating cardiomyocyte autophagy through the AMPK-mTOR signaling pathway. These findings suggest that SGLT2 inhibitor therapy may be a potential cardioprotective approach for cardiovascular complications in patients undergoing sunitinib treatment, but clinical trials are needed to confirm these effects.

FRONTIERS IN PHARMACOLOGY (2021)

Add to Collection

Review Endocrinology & Metabolism

Diabetic heart disease: A clinical update

Jake Rajbhandari et al.

Summary: Diabetes significantly raises the risk of heart disease, with much healthcare expenditure going towards managing cardiovascular complications. Diabetic heart disease is a combination of coronary artery disease, cardiac autonomic neuropathy, and diabetic cardiomyopathy, leading to a higher likelihood of premature death for affected individuals.

WORLD JOURNAL OF DIABETES (2021)

Add to Collection

Review Biochemistry & Molecular Biology

How Are Epigenetic Modifications Related to Cardiovascular Disease in Older Adults?

Mojgan Gharipour et al.

Summary: Epigenetic modifications, influenced by lifestyle and environmental factors, play a significant role in gene expression and cellular function. A healthy lifestyle, including a balanced diet, regular exercise, and stress management, is essential in preventing cardiovascular dysfunction associated with epigenetic changes.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Add to Collection

Article Cardiac & Cardiovascular Systems