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Stem Cell Reviews and Reports Feb 2019The global burden of diabetes has drastically increased over the past decades and in 2017 approximately 4 million deaths were caused by diabetes and cardiovascular... (Review)
Review
The global burden of diabetes has drastically increased over the past decades and in 2017 approximately 4 million deaths were caused by diabetes and cardiovascular complications. Diabetic cardiomyopathy is a common complication of diabetes with early manifestations of diastolic dysfunction and left ventricular hypertrophy with subsequent progression to systolic dysfunction and ultimately heart failure. An in vitro model accurately recapitulating key processes of diabetic cardiomyopathy would provide a useful tool for investigations of underlying disease mechanisms to further our understanding of the disease and thereby potentially advance treatment strategies for patients. With their proliferative capacity and differentiation potential, human induced pluripotent stem cells (iPSCs) represent an appealing cell source for such a model system and cardiomyocytes derived from induced pluripotent stem cells have been used to establish other cardiovascular related disease models. Here we review recently made advances and discuss challenges still to be overcome with regard to diabetic cardiomyopathy models, with a special focus on iPSC-based systems. Recent publications as well as preliminary data presented here demonstrate the feasibility of generating cardiomyocytes with a diabetic phenotype, displaying insulin resistance, impaired calcium handling and hypertrophy. However, capturing the full metabolic- and functional phenotype of the diabetic cardiomyocyte remains to be accomplished.
Topics: Animals; Diabetic Cardiomyopathies; Disease Models, Animal; Humans; Induced Pluripotent Stem Cells; Models, Biological; Myocytes, Cardiac
PubMed: 30343468
DOI: 10.1007/s12015-018-9858-1 -
International Journal of Molecular... Feb 2020Diabetic cardiomyopathy involves remodeling of the heart in response to diabetes that includes microvascular damage, cardiomyocyte hypertrophy, and cardiac fibrosis.... (Review)
Review
Diabetic cardiomyopathy involves remodeling of the heart in response to diabetes that includes microvascular damage, cardiomyocyte hypertrophy, and cardiac fibrosis. Cardiac fibrosis is a major contributor to diastolic dysfunction that can ultimately result in heart failure with preserved ejection fraction. Cardiac fibroblasts are the final effector cell in the process of cardiac fibrosis. This review article aims to describe the cardiac fibroblast phenotype in response to high-glucose conditions that mimic the diabetic state, as well as to explain the pathways underlying this phenotype. As such, this review focuses on studies conducted on isolated cardiac fibroblasts. We also describe molecules that appear to oppose the pro-fibrotic actions of high glucose on cardiac fibroblasts. This represents a major gap in knowledge in the field that needs to be addressed.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Fibroblasts; Humans; Hyperglycemia
PubMed: 32024054
DOI: 10.3390/ijms21030970 -
American Journal of Physiology. Heart... Jan 2019The increasing prevalence of diabetic cardiomyopathy (DCM) is an important threat to health worldwide. While left ventricular (LV) dysfunction in DCM is well recognized,... (Review)
Review
The increasing prevalence of diabetic cardiomyopathy (DCM) is an important threat to health worldwide. While left ventricular (LV) dysfunction in DCM is well recognized, the accurate detection, diagnosis, and treatment of changes in right ventricular (RV) structure and function have not been well characterized. The pathophysiology of RV dysfunction in DCM may share features with LV diastolic and systolic dysfunction, including pathways related to insulin resistance and oxidant injury, although the RV has a unique cellular origin and composition and unique biomechanical properties and is coupled to the lower-impedance pulmonary vascular bed. In this review, we discuss potential mechanisms responsible for RV dysfunction in DCM and review the imaging approaches useful for early detection, protection, and intervention strategies. Additional data are required from animal models and clinical trials to better identify the onset and features of altered RV and pulmonary vascular structure and function during the onset and progression of DCM and to determine the efficacy of early detection and treatment of RV dysfunction on clinical symptoms and outcomes.
Topics: Animals; Diabetic Cardiomyopathies; Humans; Ventricular Dysfunction, Right; Ventricular Remodeling
PubMed: 30412438
DOI: 10.1152/ajpheart.00440.2018 -
European Journal of Clinical... Apr 2021Diastolic dysfunction is traditionally believed to be the first subclinical manifestation of diabetic cardiomyopathy (DCM), leading to systolic dysfunction and then... (Review)
Review
BACKGROUND
Diastolic dysfunction is traditionally believed to be the first subclinical manifestation of diabetic cardiomyopathy (DCM), leading to systolic dysfunction and then overt heart failure. However, in the last few years, several studies suggested that systolic subclinical dysfunction measured by speckle-tracking echocardiography (STE) may appear ahead of diastolic dysfunction. In this review, the main endpoint is to show whether subclinical myocardial systolic dysfunction appears ahead of diastolic dysfunction and the implication this may have on the evolution and management of DCM.
MATERIALS AND METHODS
We performed a search in PubMed for all relevant publications on the assessment of DCM by STE from 1 June 2015 to 1 June 2020.
RESULTS AND CONCLUSIONS
The results illustrate that subclinical systolic dysfunction assessed by STE is present in early DCM stages, with or without the association of diastolic dysfunction. This could be a promising perspective for the early management of patients with DCM leading to the prevention of the overt form of disease.
Topics: Asymptomatic Diseases; Diabetic Cardiomyopathies; Diastole; Echocardiography; Humans; Systole; Ventricular Dysfunction, Left
PubMed: 33326612
DOI: 10.1111/eci.13475 -
International Journal of Molecular... Jun 2023Diabetic cardiomyopathy (DCM) is a cardiovascular disease which has been reported as a major cause of mortality worldwide for several years. Berberine (BBR) is a natural...
Diabetic cardiomyopathy (DCM) is a cardiovascular disease which has been reported as a major cause of mortality worldwide for several years. Berberine (BBR) is a natural compound extracted from a Chinese herb, with a clinically reported anti‑DCM effect; however, its molecular mechanisms have not yet been fully elucidated. The present study indicated that BBR markedly alleviated DCM by inhibiting IL‑1β secretion and the expression of gasdermin D (Gsdmd) at the post‑transcriptional level. Considering the importance of microRNAs (miRNAs/miRs) in the regulation of the post‑transcriptional process of specific genes, the ability of BBR to upregulate the expression levels of miR‑18a‑3p by activating its promoter (‑1,000/‑500) was examined. Notably, miR‑18a‑3p targeted Gsdmd and abated pyroptosis in high glucose‑treated H9C2 cells. Moreover, miR‑18a‑3p overexpression inhibited Gsdmd expression and improved biomarkers of cardiac function in a rat model of DCM. On the whole, the findings of the present study indicate that BBR alleviates DCM by inhibiting miR‑18a‑3p‑mediated Gsdmd activation; thus, BBR may be considered a potential therapeutic agent for the treatment of DCM.
Topics: Animals; Rats; Berberine; Diabetes Mellitus; Diabetic Cardiomyopathies; Inflammasomes; MicroRNAs; Pyroptosis
PubMed: 37114562
DOI: 10.3892/ijmm.2023.5252 -
Current Problems in Cardiology Jan 2011
Topics: Cardiac Imaging Techniques; Diabetic Cardiomyopathies; Humans
PubMed: 21147360
DOI: 10.1016/j.cpcardiol.2010.10.002 -
Advances in Experimental Medicine and... 2017Diabetic subjects are at risk of developing cardiovascular disease, which accounts for 60-80% of diabetes-related mortality. Atherosclerosis is still considered as a... (Review)
Review
Diabetic subjects are at risk of developing cardiovascular disease, which accounts for 60-80% of diabetes-related mortality. Atherosclerosis is still considered as a leading cause of heart failure in diabetic patients, but it could also be an intrinsic and long-term effect of contractile cardiac cells malfunction, known as diabetic cardiomyopathy (DCM). Pathologically, this cardiac dysfunction is manifested by inflammation, apoptosis, fibrosis, hypertrophy and altered cardiomyocytes metabolism. However, the underlying molecular mechanisms of DCM pathophysiology are not clearly understood. Recent and several studies have suggested that exosomes are contributed to the regulation of cell-to-cell communication. Therefore, their in-depth investigation can interpret the complex pathophysiology of DCM. Structurally, exosomes are membrane-bounded vesicles (10-200 nm in diameter), which are actively released from all types of cells and detected in all biological fluids. They carry a wide array of bioactive molecules, including mRNAs, none-coding RNAs (e.g., microRNAs, lncRNAs, circRNAs, etc), proteins and lipids. Importantly, the abundance and nature of loaded molecules inside exosomes fluctuate with cell types and pathological conditions. This chapter summarizes currently available studies on the exosomes' role in the regulation of diabetic cardiomyopathy. Specifically, the advances on the pathological effects of exosomes in diabetic cardiomyopathy as well as the therapeutic potentials and perspectives are also discussed.
Topics: Animals; Diabetic Cardiomyopathies; Exosomes; Humans; Myocardium; Signal Transduction
PubMed: 28936736
DOI: 10.1007/978-981-10-4397-0_8 -
Heart Failure Reviews Nov 2016The worldwide increase trend in the prevalence of diabetes has highlighted the need for increased research efforts into treatment options for both the disease itself and... (Review)
Review
The worldwide increase trend in the prevalence of diabetes has highlighted the need for increased research efforts into treatment options for both the disease itself and its associated complications. Diabetes has been widely recognized as a major risk factor for cardiovascular diseases, such as coronary heart disease and hypertension. Diabetic cardiomyopathy (DCM) is a main complication of diabetes, contributing to specific forms of heart failure independent from ischemia or hypertension. Without considerably effective approaches, a dire need exists to further explore the mechanisms and potential therapeutic strategies to prevent or reverse the progression of DCM. In the past decades, stem cell-based therapies have held promises to various diseases including DCM. The aim of the present review was to summarize the current literature with regard to the pathological changes of diabetic cardiomyopathy, endogenous stem cells in diabetes, and the exogenous stem cells transplantation for DCM. If the best use is made of the advantages of stem cells and their mechanism of action is explicitly explored, stem cell-based therapies could served as an important tool for the prevention and treatment of DCM patients.
Topics: Diabetic Cardiomyopathies; Heart Failure; Humans; Insulin Resistance; Stem Cell Transplantation; Treatment Outcome
PubMed: 27221074
DOI: 10.1007/s10741-016-9565-4 -
Heart Failure Reviews Jan 2014Although heart disease due to diabetes is mainly associated with complications of the large vessels, microvascular abnormalities are also considered to be involved in... (Review)
Review
Although heart disease due to diabetes is mainly associated with complications of the large vessels, microvascular abnormalities are also considered to be involved in altering cardiac structure and function. Three major defects, such as endothelial dysfunction, alteration in the production/release of hormones, and shift in metabolism of smooth muscle cells, have been suggested to produce damage to the small arteries and capillaries (microangiopathy) due to hyperglycemia, and promote the development of diabetic cardiomyopathy. These factors may either act alone or in combination to produce oxidative stress as well as changes in cellular signaling and gene transcription, which in turn cause vasoconstriction and structural remodeling of the coronary vessels. Such alterations in microvasculature produce hypoperfusion of the myocardium and thereby lower the energy status resulting in changes in Ca(2+)-handling, apoptosis, and decreased cardiac contractile force. This article discusses diabetes-induced mechanisms of microvascular damage leading to cardiac dysfunction that is characterized by myocardial dilatation, cardiac hypertrophy as well as early diastolic and late systolic defects. Metabolic defects and changes in neurohumoral system due to diabetes, which promote disturbances in vascular homeostasis, are highlighted. In addition, increase in the vulnerability of the diabetic heart to the development of heart failure and the signaling pathways integrating nuclear factor κB and protein kinase C in diabetic cardiomyopathy are also described for comparison.
Topics: Diabetic Angiopathies; Diabetic Cardiomyopathies; Disease Progression; Endothelium, Vascular; Humans; Myocardium; Oxidative Stress; Vasodilation; Ventricular Remodeling
PubMed: 23456446
DOI: 10.1007/s10741-013-9378-7 -
The Journal of Pharmacy and Pharmacology Nov 2022Diabetic cardiomyopathy (DCM) is an end-point macrovascular complication associated with increased morbidity and mortality in 12% of diabetic patients. MicroRNAs... (Review)
Review
INTRODUCTION
Diabetic cardiomyopathy (DCM) is an end-point macrovascular complication associated with increased morbidity and mortality in 12% of diabetic patients. MicroRNAs (miRNAs) are small noncoding RNAs that can act as cardioprotective or cardiotoxic agents in DCM.
METHODS
We used PubMed as a search engine to collect and analyse data in published articles on the role of miRNAs on the pathophysiology, diagnosis and treatment of DCM.
RESULTS
MiRNAs play an essential role in the pathophysiology, diagnosis and treatment of DCM due to their distinct gene expression patterns in diabetic patients compared to healthy individuals. Advances in gene therapy have led to the discovery of potential circulating miRNAs, which can be used as biomarkers for DCM diagnosis and prognosis. Furthermore, targeted miRNA therapies in preclinical and clinical studies, such as using miRNA mimics and anti-miRNAs, have yielded promising results. Application of miRNA mimics and anti-miRNAs via different nanodrug delivery systems alleviate hypertrophy, fibrosis, oxidative stress and apoptosis of cardiomyocytes.
CONCLUSION
MiRNAs serve as attractive potential targets for DCM diagnosis, prognosis and treatment due to their distinctive expression profile in DCM development.
Topics: Humans; Biomarkers; Diabetes Mellitus; Diabetic Cardiomyopathies; Fibrosis; Genetic Therapy; MicroRNAs
PubMed: 36130185
DOI: 10.1093/jpp/rgac066