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Biomedicine & Pharmacotherapy =... Jan 2023The pathophysiological mechanisms of diabetic cardiomyopathy have been extensively studied, but there is still a lack of effective prevention and treatment methods. The... (Review)
Review
The pathophysiological mechanisms of diabetic cardiomyopathy have been extensively studied, but there is still a lack of effective prevention and treatment methods. The ability of flavonoids to protect the heart from diabetic cardiomyopathy has been extensively described. In recent years, epigenetics has received increasing attention from scholars in exploring the etiology and treatment of diabetes and its complications. DNA methylation, histone modifications and non-coding RNAs play key functions in the development, maintenance and progression of diabetic cardiomyopathy. Hence, prevention or reversal of the epigenetic alterations that have occurred during the development of diabetic cardiomyopathy may alleviate the personal and social burden of the disease. Flavonoids can be used as natural epigenetic modulators in alternative therapies for diabetic cardiomyopathy. In this review, we discuss the epigenetic effects of different flavonoid subtypes in diabetic cardiomyopathy and summarize the evidence from preclinical and clinical studies that already exist. However, limited research is available on the potential beneficial effects of flavonoids on the epigenetics of diabetic cardiomyopathy. In the future, clinical trials in which different flavonoids exert their antidiabetic and cardioprotective effects through various epigenetic mechanisms should be further explored.
Topics: Humans; Diabetic Cardiomyopathies; Flavonoids; Epigenesis, Genetic; Epigenomics; DNA Methylation; Diabetes Mellitus
PubMed: 36399824
DOI: 10.1016/j.biopha.2022.114025 -
Diabetes & Metabolism Journal Mar 2021Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a... (Review)
Review
Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.
Topics: Animals; Diabetes Mellitus; Diabetic Cardiomyopathies; Heart Failure; Humans; Models, Animal; Oxidative Stress; Renin-Angiotensin System
PubMed: 33813812
DOI: 10.4093/dmj.2020.0285 -
International Journal of Molecular... Apr 2020Metabolic syndrome, diabetes, and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is... (Review)
Review
Metabolic syndrome, diabetes, and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. In addition, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.
Topics: Animals; Diabetes Mellitus; Diabetic Cardiomyopathies; Disease Management; Disease Susceptibility; Exercise; Humans; Ischemic Preconditioning; Metabolic Networks and Pathways; Myocardial Ischemia; Myocardial Reperfusion Injury
PubMed: 32326182
DOI: 10.3390/ijms21082896 -
Critical Reviews in Eukaryotic Gene... 2021Diabetic cardiomyopathy is characterized as abnormal function and structure of myocardium associated with diabetes irrespective of other cardiac risk factors like... (Review)
Review
Diabetic cardiomyopathy is characterized as abnormal function and structure of myocardium associated with diabetes irrespective of other cardiac risk factors like hypertension or coronary artery disease (CAD). The pathogenesis of DCM was not well understood in the past due to its complexity but it has been discovered recently. Various factors are found to be associated with the onset of DCM including impaired calcium handling, remodeling of extracellular matrix (ECM), increased oxidative stress, altered metabolism, mitochondrial dysfunction, and endothelial dysfunction. Micro-RNAs (miRNAs) are also found to be of great importance in the pathogenesis of DCM. Different miRNAs like miR-126, miR-24, miR-1, miR-155, miR-499, and miR-199a are found to be associated with different types of heart diseases like CAD and myocardial infarction. Studies have shown that the miRNA plays a crucial role in the development of DCM and it was found that the expression levels of different miRNAs differ in patients as compared to healthy individuals. This review focuses on the pathogenesis of DCM and various factors involved in the onset of diabetic car-diomyopathy. Moreover, the probable role of miRNA in the pathogenesis of DCM is also discussed.
Topics: Animals; Calcium; Diabetic Cardiomyopathies; Extracellular Matrix; Gene Expression Regulation; Humans; MicroRNAs; Mitochondria; Oxidative Stress; Risk Factors; Signal Transduction
PubMed: 33639058
DOI: 10.1615/CritRevEukaryotGeneExpr.2021037533 -
Archives of Cardiovascular Diseases Nov 2021Diabetes mellitus is a metabolic disorder with a chronic hyperglycaemic state. Cardiovascular diseases are the primary cause of mortality in patients with diabetes.... (Review)
Review
Diabetes mellitus is a metabolic disorder with a chronic hyperglycaemic state. Cardiovascular diseases are the primary cause of mortality in patients with diabetes. Increasing evidence supports the existence of diabetic cardiomyopathy, a cardiac dysfunction with impaired cardiac contraction and relaxation, independent of coronary and/or valvular complications. Diabetic cardiomyopathy can lead to heart failure. Several preclinical and clinical studies have aimed to decipher the underlying mechanisms of diabetic cardiomyopathy. Among all the co-factors, hyperglycaemia seems to play an important role in this pathology. Hyperglycaemia has been shown to alter cardiac metabolism and function through several deleterious mechanisms, such as oxidative stress, inflammation, accumulation of advanced glycated end-products and upregulation of the hexosamine biosynthesis pathway. These mechanisms are responsible for the activation of hypertrophic pathways, epigenetic modifications, mitochondrial dysfunction, cell apoptosis, fibrosis and calcium mishandling, leading to cardiac stiffness, as well as contractile and relaxation dysfunction. This review aims to describe the hyperglycaemic-induced alterations that participate in diabetic cardiomyopathy, and their correlation with the severity of the disease and patient mortality, and to provide an overview of cardiac outcomes of glucose-lowering therapy.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Heart; Heart Failure; Humans; Hyperglycemia; Oxidative Stress
PubMed: 34627704
DOI: 10.1016/j.acvd.2021.08.004 -
Minerva Cardiology and Angiology Jun 2022Diabetic patients are prone to suffer from cardiovascular disease, specifically from ischemic heart disease and diabetic cardiomyopathy, which have a huge impact on... (Review)
Review
Diabetic patients are prone to suffer from cardiovascular disease, specifically from ischemic heart disease and diabetic cardiomyopathy, which have a huge impact on morbidity and mortality worldwide. Cardiac fibrosis due to alteration of the extracellular matrix (ECM) remodeling is often observed in diabetes and myocardial fibrosis is an important part of cardiac remodeling that leads to heart failure and death. At single-cell level, the ECM govern, metabolism, motility, orientation, and proliferation. However, in pathological condition such as diabetes, changes in ECM lead to fibrosis and subsequently cardiac stiffness and cardiomyocytes dysfunction. Antidiabetic drugs, particularly sodium-glucose cotransporter-2 (SGLT2) inhibitors have antifibrotic effects and may promote ECM reverse remodeling. In this review, the mechanisms, and the role of ECM remodeling and reverse remodeling as a potential therapeutic target for diabetic cardiomyopathy are discussed.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Extracellular Matrix; Fibrosis; Heart Failure; Humans; Myocytes, Cardiac
PubMed: 34713679
DOI: 10.23736/S2724-5683.21.05794-X -
Frontiers in Endocrinology 2023Diabetic cardiomyopathy (DCM), a main cardiovascular complication of diabetes, can eventually develop into heart failure and affect the prognosis of patients. Myocardial... (Review)
Review
Diabetic cardiomyopathy (DCM), a main cardiovascular complication of diabetes, can eventually develop into heart failure and affect the prognosis of patients. Myocardial fibrosis is the main factor causing ventricular wall stiffness and heart failure in DCM. Early control of myocardial fibrosis in DCM is of great significance to prevent or postpone the progression of DCM to heart failure. A growing body of evidence suggests that cardiomyocytes, immunocytes, and endothelial cells involve fibrogenic actions, however, cardiac fibroblasts, the main participants in collagen production, are situated in the most central position in cardiac fibrosis. In this review, we systematically elaborate the source and physiological role of myocardial fibroblasts in the context of DCM, and we also discuss the potential action and mechanism of cardiac fibroblasts in promoting fibrosis, so as to provide guidance for formulating strategies for prevention and treatment of cardiac fibrosis in DCM.
Topics: Humans; Diabetic Cardiomyopathies; Endothelial Cells; Signal Transduction; Myocytes, Cardiac; Fibroblasts; Heart Failure; Fibrosis; Diabetes Mellitus
PubMed: 37065745
DOI: 10.3389/fendo.2023.1162754 -
Acta Diabetologica Sep 2020Diabetes cardiomyopathy is a specific form of cardiac disease characteristic for diabetic patients. Development of echocardiography enabled diagnosis of diabetic... (Review)
Review
Diabetes cardiomyopathy is a specific form of cardiac disease characteristic for diabetic patients. Development of echocardiography enabled diagnosis of diabetic cardiomyopathy significantly before the occurrence of heart failure. Previously was believed that left ventricular (LV) diastolic dysfunction represents the first detectable stage of diabetic cardiomyopathy. However, speckle tracking imaging and strain evaluation showed that mechanical changes occur before LV diastolic dysfunction. Nevertheless, it seems that the first detectable stage of diabetic cardiomyopathy is myocardial interstitial fibrosis, which currently could be diagnosed predominantly by cardiac magnetic resonance. T1 mapping evaluation before and after contrast injection enables assessment of extracellular volume (ECV) and provides qualitative and quantitative assessment of interstitial myocardial fibrosis in diabetic patients. Studies showed a strong correlation between ECV-parameter of interstitial fibrosis and level of glycated hemoglobin-main parameter of glucose control in diabetes. This stage of fibrosis is still not LV hypertrophy and it is reversible, which is of a great importance because of timely initiation of treatment. The necessity for early diagnose is significantly increasing due to the fact that diabetes and arterial hypertension are concomitant disorders in the large number of diabetic patients and it has been known that the risk of interstitial myocardial fibrosis is multiplied in patients with both conditions. Future follow-up investigations are essential to determine the causal relationship between interstitial fibrosis and outcome in these patients. The aim of this review was to summarize the current knowledge and clinical usefulness of CMR in diabetic patients.
Topics: Diabetic Cardiomyopathies; Echocardiography; Heart; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Myocardium; Predictive Value of Tests; Ventricular Dysfunction, Left
PubMed: 32285200
DOI: 10.1007/s00592-020-01528-2 -
Diabetes & Vascular Disease Research 2023Over half a billion adults across the world have diabetes mellitus (DM). This has a wide-ranging impact on their health, including more than doubling their risk of major... (Review)
Review
Over half a billion adults across the world have diabetes mellitus (DM). This has a wide-ranging impact on their health, including more than doubling their risk of major cardiovascular events, in comparison to age-sex matched individuals without DM. Notably, the risk of heart failure is particularly increased, even when coronary artery disease and hypertension are not present. Macro- and micro-vascular complications related to endothelial cell (EC) dysfunction are a systemic feature of DM and can affect the heart. However, it remains unclear to what extent these and other factors underpin myocardial dysfunction and heart failure linked with DM. Use of unbiased 'omics approaches to profile the molecular environment of the heart offers an opportunity to identify novel drivers of cardiac dysfunction in DM. Multiple transcriptomics studies have characterised the whole myocardium or isolated cardiac ECs. We present a systematic summary of relevant studies, which identifies common themes including alterations in both myocardial fatty acid metabolism and inflammation. These findings prompt further research focussed on these processes to validate potentially causal factors for prioritisation into therapeutic development pipelines.
Topics: Adult; Humans; Myocardium; Diabetic Cardiomyopathies; Heart Failure; Diabetes Mellitus, Type 2; Gene Expression Profiling
PubMed: 38116627
DOI: 10.1177/14791641231205428 -
Minerva Cardiology and Angiology Jun 2022Diabetes mellitus is emerging as a major risk factor for heart failure. Diabetic cardiomyopathy is defined as a myocardial dysfunction that is not caused by underlying... (Review)
Review
Diabetes mellitus is emerging as a major risk factor for heart failure. Diabetic cardiomyopathy is defined as a myocardial dysfunction that is not caused by underlying hypertension or coronary artery disease. Studies about clinical features, natural history and outcomes of the disease are few and often conflicting, because a universally accepted operative definition of diabetic cardiomyopathy is still lacking. Hyperglycemia and related metabolic and endocrine disorders are the triggering factors of myocardial damage in diabetic cardiomyopathy through multiple mechanisms. Among these mechanisms, inflammation has a relevant role, similar to other chronic myocardial disease, such as hypertensive or ischemic heart disease. A balance between inflammatory damage and healing processes is fundamental for homeostasis of myocardial tissue, whereas diabetes mellitus produces an imbalance, promoting inflammation and delaying healing. Therefore, diabetes-related chronic inflammatory state can produce a progressive qualitative deterioration of myocardial tissue, which reflects on progressive left ventricular functional impairment, which can be either diastolic, with prevalent myocardial hypertrophy, or systolic, with prevalent myocardial fibrosis. The aim of this narrative review is to summarize the existing evidence about the role of inflammation in diabetic cardiomyopathy onset and development. Ultimately, potential pharmacological strategies targeting inflammatory response will be reviewed and discussed.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Heart Failure; Humans; Hyperglycemia; Hypertension; Inflammation; Myocardium; Ventricular Dysfunction, Left
PubMed: 33427423
DOI: 10.23736/S2724-5683.20.05454-7