Epigenetics of methylation modifications in diabetic cardiomyopathy

Hao, Jing; Liu, Yao

doi:10.3389/fendo.2023.1119765

Cited by 5 publications

(4 citation statements)

References 112 publications

(124 reference statements)

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“…It has been con rmed that ferroptosis is involved in metabolic cardiomyopathy. Although ferroptosis has been demonstrated to be involved in ischemic cardiomyopathy [32] and diabetic cardiomyopathy [33], to the best of our knowledge, whether it is also involved in the development of obesity cardiomyopathy remains unknown. As shown in Fig.…”

Section: Discussionmentioning

confidence: 94%

Dapagliflozin alleviates high-fat-induced obesity cardiomyopathy by inhibiting ferroptosis

Chen,

Shi,

Xuan

et al. 2023

Preprint

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Dapagliflozin (Dapa), a selective sodium-glucose cotransporter 2 inhibitor, not only has a stable hypoglycemic function but also exerts a protective effect in cardiovascular diseases. The present study aimed to investigate whether Dapa could effectively protect high-fat diet (HFD)-induced obesity-related cardiomyocytes and its mechanism. Rats were fed with a HFD for 16 weeks and the obesity cardiomyopathy was confirmed by testing of metabolic parameters. The results demonstrated that Dapa treatment led to more obvious weight loss and a lower Lee’s index. Furthermore, Dapa administration reduced the lipid levels, including total cholesterol and low-density lipoprotein cholesterol levels, and improved the insulin sensitivity/resistance index, whereas the blood pressure was not markedly different after Dapa intervention. Echocardiography and histological analysis revealed that Dapa could effectively alleviate obesity-induced the myofibrils dissolved, collagen deposition and mitochondrial damage, and finally improved the heart function and cardiac remodeling. The present study also emphasized the vital role of Dapa in the protection obesity-related cardiac dysfunction and cardiac remodeling by inhibiting ferroptosis. Dapa treatment ameliorated the ferroptosis-related changes by attenuating iron ion deposition and decreased over-activation of the key factors of ferroptosis, including glutathione peroxidase 4, solute carrier family 7 member 11, transferrin 1 and ferritin heavy chain 1, in cardiomyocytes. In conclusion, Dapa exerted a direct protective effect against obesity cardiomyopathy by inhibiting ferroptosis.

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Section: Discussionmentioning

confidence: 94%

Dapagliflozin alleviates high-fat-induced obesity cardiomyopathy by inhibiting ferroptosis

Chen,

Shi,

Xuan

et al. 2023

Preprint

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“…Diabetic cardiomyopathy is defined as myocardial disease in diabetic patients which cannot be attributed to any common cardiovascular etiologies or risk factors ( 104 ). The condition can be seen in 12% of diabetics and its prevalence is expected to rise exponentially in the coming years ( 105 ).…”

Section: Epigenetic Modifications In the Complications Of T2dmmentioning

confidence: 99%

Unraveling the epigenetic fabric of type 2 diabetes mellitus: pathogenic mechanisms and therapeutic implications

Jazieh,

Arabi,

Asim

et al. 2024

Front. Endocrinol.

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Type 2 diabetes mellitus (T2DM) is a rapidly escalating global health concern, with its prevalence projected to increase significantly in the near future. This review delves into the intricate role of epigenetic modifications - including DNA methylation, histone acetylation, and micro-ribonucleic acid (miRNA) expression - in the pathogenesis and progression of T2DM. We critically examine how these epigenetic changes contribute to the onset and exacerbation of T2DM by influencing key pathogenic processes such as obesity, insulin resistance, β-cell dysfunction, cellular senescence, and mitochondrial dysfunction. Furthermore, we explore the involvement of epigenetic dysregulation in T2DM-associated complications, including diabetic retinopathy, atherosclerosis, neuropathy, and cardiomyopathy. This review highlights recent studies that underscore the diagnostic and therapeutic potential of targeting epigenetic modifications in T2DM. We also provide an overview of the impact of lifestyle factors such as exercise and diet on the epigenetic landscape of T2DM, underscoring their relevance in disease management. Our synthesis of the current literature aims to illuminate the complex epigenetic underpinnings of T2DM, offering insights into novel preventative and therapeutic strategies that could revolutionize its management.

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“…The synergistic effects of these factors may involve complex interactions between genetic and environmental factors, leading to dysregulation of pathways related to endothelial function, inflammation, and oxidative stress ( 140 ). Epigenetic modifications associated with hypertension and T2DM, such as DNA methylation and histone modifications, may interact synergistically to alter gene expression patterns related to CAD development ( 141 ). For example, hypermethylation of genes involved in lipid metabolism and endothelial function may exacerbate atherosclerosis in individuals with both conditions ( 142 ).…”

Section: Epigenetic Interplay Between Hypertension and Coronary Arter...mentioning

confidence: 99%

Epigenetics of hypertension as a risk factor for the development of coronary artery disease in type 2 diabetes mellitus

Karabaeva,

Vochshenkova,

Mussin

et al. 2024

Front. Endocrinol.

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Hypertension, a multifaceted cardiovascular disorder influenced by genetic, epigenetic, and environmental factors, poses a significant risk for the development of coronary artery disease (CAD) in individuals with type 2 diabetes mellitus (T2DM). Epigenetic alterations, particularly in histone modifications, DNA methylation, and microRNAs, play a pivotal role in unraveling the complex molecular underpinnings of blood pressure regulation. This review emphasizes the crucial interplay between epigenetic attributes and hypertension, shedding light on the prominence of DNA methylation, both globally and at the gene-specific level, in essential hypertension. Additionally, histone modifications, including acetylation and methylation, emerge as essential epigenetic markers linked to hypertension. Furthermore, microRNAs exert regulatory influence on blood pressure homeostasis, targeting key genes within the aldosterone and renin-angiotensin pathways. Understanding the intricate crosstalk between genetics and epigenetics in hypertension is particularly pertinent in the context of its interaction with T2DM, where hypertension serves as a notable risk factor for the development of CAD. These findings not only contribute to the comprehensive elucidation of essential hypertension but also offer promising avenues for innovative strategies in the prevention and treatment of cardiovascular complications, especially in the context of T2DM.

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Epigenetics of methylation modifications in diabetic cardiomyopathy

Cited by 5 publications

References 112 publications

Dapagliflozin alleviates high-fat-induced obesity cardiomyopathy by inhibiting ferroptosis

Dapagliflozin alleviates high-fat-induced obesity cardiomyopathy by inhibiting ferroptosis

Unraveling the epigenetic fabric of type 2 diabetes mellitus: pathogenic mechanisms and therapeutic implications

Epigenetics of hypertension as a risk factor for the development of coronary artery disease in type 2 diabetes mellitus

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