-
Comprehensive Physiology Mar 2017Diabetic cardiomyopathy (DCM) was first recognized more than four decades ago and occurred independent of cardiovascular diseases or hypertension in both type 1 and type... (Review)
Review
Diabetic cardiomyopathy (DCM) was first recognized more than four decades ago and occurred independent of cardiovascular diseases or hypertension in both type 1 and type 2 diabetic patients. The exact mechanisms underlying this disease remain incompletely understood. Several pathophysiological bases responsible for DCM have been proposed, including the presence of hyperglycemia, nonenzymatic glycosylation of large molecules (e.g., proteins), energy metabolic disturbance, mitochondrial damage and dysfunction, impaired calcium handling, reactive oxygen species formation, inflammation, cardiac cell death, and cardiac hypertrophy and fibrosis, leading to impairment of cardiac contractile functions. Increasing evidence also indicates the phenomenon called "metabolic memory" for diabetes-induced cardiovascular complications, for which epigenetic modulation seemed to play an important role, suggesting that the aforementioned pathogenic bases may be regulated by epigenetic modification. Therefore, this review aims at briefly summarizing the current understanding of the pathophysiological bases for DCM. Although how epigenetic mechanisms play a role remains incompletely understood now, extensive clinical and experimental studies have implicated its importance in regulating the cardiac responses to diabetes, which are believed to shed insight into understanding of the pathophysiological and epigenetic mechanisms for the development of DCM and its possible prevention and/or therapy. © 2017 American Physiological Society. Compr Physiol 7:693-711, 2017.
Topics: Animals; Apoptosis; Cardiomegaly; DNA Methylation; Diabetic Cardiomyopathies; Epigenesis, Genetic; Extracellular Matrix; Fibrosis; Humans; MicroRNAs; Myocardium; Ventricular Dysfunction, Left
PubMed: 28333387
DOI: 10.1002/cphy.c160021 -
Cell Stress & Chaperones Nov 2023Diabetic cardiomyopathy describes decreased myocardial function in diabetic patients in the absence of other heart diseases such as myocardial ischemia and hypertension.... (Review)
Review
Diabetic cardiomyopathy describes decreased myocardial function in diabetic patients in the absence of other heart diseases such as myocardial ischemia and hypertension. Recent studies have defined numerous molecular interactions and signaling events that may account for deleterious changes in mitochondrial dynamics and functions influenced by hyperglycemic stress. A metabolic switch from glucose to fatty acid oxidation to fuel ATP synthesis, mitochondrial oxidative injury resulting from increased mitochondrial ROS production and decreased antioxidant capacity, enhanced mitochondrial fission and defective mitochondrial fusion, impaired mitophagy, and blunted mitochondrial biogenesis are major signatures of mitochondrial pathologies during diabetic cardiomyopathy. This review describes the molecular alterations underlying mitochondrial abnormalities associated with hyperglycemia and discusses their influence on cardiomyocyte viability and function. Based on basic research findings and clinical evidence, diabetic treatment standards and their impact on mitochondrial function, as well as mitochondria-targeted therapies of potential benefit for diabetic cardiomyopathy patients, are also summarized.
Topics: Humans; Diabetic Cardiomyopathies; Mitochondria; Myocytes, Cardiac; Myocardial Ischemia; Cardiovascular Diseases; Mitochondrial Dynamics; Diabetes Mellitus
PubMed: 37405612
DOI: 10.1007/s12192-023-01361-w -
International Journal of Cardiology Oct 2022
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Fibrosis; Humans; Myocardium
PubMed: 35868356
DOI: 10.1016/j.ijcard.2022.07.028 -
Trends in Molecular Medicine Jun 2021Diabetic cardiomyopathy is the leading cause of death among people with diabetes. Despite its severity and poor prognosis, there are currently no approved specific drugs... (Review)
Review
Diabetic cardiomyopathy is the leading cause of death among people with diabetes. Despite its severity and poor prognosis, there are currently no approved specific drugs to prevent or even treat diabetic cardiomyopathy. There is a need to understand the pathogenic mechanisms underlying the development of diabetic cardiomyopathy to design new therapeutic strategies. These mechanisms are complex and intricate and include metabolic dysregulation, inflammation, oxidative stress, fibrosis, and apoptosis. Sirtuins, a group of deacetylase enzymes, play an important role in all these processes and are, therefore, potential molecular targets for treating this disease. In this review, we discuss the role of sirtuins in the heart, focusing on their contribution to the pathogenesis of diabetic cardiomyopathy and how their modulation could be therapeutically useful.
Topics: Animals; Diabetes Mellitus; Diabetic Cardiomyopathies; Humans; Inflammation; Oxidative Stress; Signal Transduction; Sirtuins
PubMed: 33839024
DOI: 10.1016/j.molmed.2021.03.004 -
International Journal of Molecular... Oct 2015Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular... (Review)
Review
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS). ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.
Topics: Animals; Diabetic Cardiomyopathies; Fibrosis; Humans; Oxidative Stress
PubMed: 26512646
DOI: 10.3390/ijms161025234 -
Heart Failure Reviews Mar 2013Since diabetic cardiomyopathy was first reported four decades ago, substantial information on its pathogenesis and clinical features has accumulated. In the heart,... (Review)
Review
Since diabetic cardiomyopathy was first reported four decades ago, substantial information on its pathogenesis and clinical features has accumulated. In the heart, diabetes enhances fatty acid metabolism, suppresses glucose oxidation, and modifies intracellular signaling, leading to impairments in multiple steps of excitation-contraction coupling, inefficient energy production, and increased susceptibility to ischemia/reperfusion injury. Loss of normal microvessels and remodeling of the extracellular matrix are also involved in contractile dysfunction of diabetic hearts. Use of sensitive echocardiographic techniques (tissue Doppler imaging and strain rate imaging) and magnetic resonance spectroscopy enables detection of diabetic cardiomyopathy at an early stage, and a combination of the modalities allows differentiation of this type of cardiomyopathy from other organic heart diseases. Circumstantial evidence to date indicates that diabetic cardiomyopathy is a common but frequently unrecognized pathological process in asymptomatic diabetic patients. However, a strategy for prevention or treatment of diabetic cardiomyopathy to improve its prognosis has not yet been established. Here, we review both basic and clinical studies on diabetic cardiomyopathy and summarize problems remaining to be solved for improving management of this type of cardiomyopathy.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Disease Management; Echocardiography, Doppler; Heart; Heart Failure; Humans; Signal Transduction
PubMed: 22453289
DOI: 10.1007/s10741-012-9313-3 -
Journal of Diabetes Research 2015Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by alterations in structure and contractility of the myocardium. This pathology is initiated by... (Review)
Review
Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by alterations in structure and contractility of the myocardium. This pathology is initiated by changes in energy substrates and occurs in the absence of atherothrombosis, hypertension, or other cardiomyopathies. Inflammation, hypertrophy, fibrosis, steatosis, and apoptosis in the myocardium have been studied in numerous diabetic experimental models in animals, mostly rodents. Type I and type II diabetes were induced by genetic manipulation, pancreatic toxins, and fat and sweet diets, and animals recapitulate the main features of human diabetes and related cardiomyopathy. In this review we update and discuss the main experimental models of diabetic cardiomyopathy, analysing the associated metabolic, structural, and functional abnormalities, and including current tools for detection of these responses. Also, novel experimental models based on genetic modifications of specific related genes have been discussed. The study of specific pathways or factors responsible for cardiac failures may be useful to design new pharmacological strategies for diabetic patients.
Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Disease Models, Animal; Heart; Myocardium
PubMed: 25973429
DOI: 10.1155/2015/656795 -
Biochimica Et Biophysica Acta.... Aug 2017Diabetic cardiomyopathy is a chronic and irreversible heart complication in diabetic patients, and is characterized by complex pathophysiologic events including early... (Review)
Review
Diabetic cardiomyopathy is a chronic and irreversible heart complication in diabetic patients, and is characterized by complex pathophysiologic events including early diastolic dysfunction, cardiac hypertrophy, ventricular dilation and systolic dysfunction, eventually resulting in heart failure. Despite these characteristics, the underlying mechanisms leading to diabetic cardiomyopathy are still elusive. Recent studies have implicated microRNA, a small and highly conserved non-coding RNA molecule, in the etiology of diabetes and its complications, suggesting a potentially novel approach for the diagnosis and treatment of diabetic cardiomyopathy. This brief review aims at capturing recent studies related to the role of microRNA in diabetic cardiomyopathy. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.
Topics: Animals; Diabetic Cardiomyopathies; Humans; MicroRNAs
PubMed: 28344129
DOI: 10.1016/j.bbadis.2017.03.013 -
Cells Jan 2022The incidence and prevalence of diabetes mellitus (DM) are increasing worldwide, and the resulting cardiac complications are the leading cause of death. Among these... (Review)
Review
The incidence and prevalence of diabetes mellitus (DM) are increasing worldwide, and the resulting cardiac complications are the leading cause of death. Among these complications is diabetes-induced cardiomyopathy (DCM), which is the consequence of a pro-inflammatory condition, oxidative stress and fibrosis caused by hyperglycemia. Cardiac remodeling will lead to an imbalance in cell survival and death, which can promote cardiac dysfunction. Since the conventional treatment of DM generally does not address the prevention of cardiac remodeling, it is important to develop new alternatives for the treatment of cardiovascular complications induced by DM. Thus, therapy with mesenchymal stem cells has been shown to be a promising approach for the prevention of DCM because of their anti-apoptotic, anti-fibrotic and anti-inflammatory effects, which could improve cardiac function in patients with DM.
Topics: Animals; Clinical Trials as Topic; Diabetic Cardiomyopathies; Epigenesis, Genetic; Humans; Mesenchymal Stem Cell Transplantation; Models, Biological; Vascular Remodeling
PubMed: 35053356
DOI: 10.3390/cells11020240 -
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