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Heart (British Cardiac Society) Feb 2019
Topics: Biomarkers; Cardiac Imaging Techniques; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Heart Failure; Humans; Metabolism; Preventive Health Services; Prognosis; Ventricular Remodeling
PubMed: 30337334
DOI: 10.1136/heartjnl-2016-310342 -
Cardiovascular Diabetology Feb 2017Diabetic cardiomyopathy (DCM) is a cardiac dysfunction which affects approximately 12% of diabetic patients, leading to overt heart failure and death. However, there is... (Review)
Review
Diabetic cardiomyopathy (DCM) is a cardiac dysfunction which affects approximately 12% of diabetic patients, leading to overt heart failure and death. However, there is not an efficient and specific methodology for DCM diagnosis, possibly because molecular mechanisms are not fully elucidated, and it remains asymptomatic for many years. Also, DCM frequently coexists with other comorbidities such as hypertension, obesity, dyslipidemia, and vasculopathies. Thus, human DCM is not specifically identified after heart failure is established. In this sense, echocardiography has been traditionally considered the gold standard imaging test to evaluate the presence of cardiac dysfunction, although other techniques may cover earlier DCM detection by quantification of altered myocardial metabolism and strain. In this sense, Phase-Magnetic Resonance Imaging and 2D/3D-Speckle Tracking Echocardiography may potentially diagnose and stratify diabetic patients. Additionally, this information could be completed with a quantification of specific plasma biomarkers related to related to initial stages of the disease. Cardiotrophin-1, activin A, insulin-like growth factor binding protein-7 (IGFBP-7) and Heart fatty-acid binding protein have demonstrated a stable positive correlation with cardiac hypertrophy, contractibility and steatosis responses. Thus, we suggest a combination of minimally-invasive diagnosis tools for human DCM recognition based on imaging techniques and measurements of related plasma biomarkers.
Topics: Diabetic Cardiomyopathies; Echocardiography; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon
PubMed: 28231848
DOI: 10.1186/s12933-017-0506-x -
The Korean Journal of Internal Medicine May 2017The global burden of diabetes mellitus and its related complications are currently increasing. Diabetes mellitus affects the heart through various mechanisms including... (Review)
Review
The global burden of diabetes mellitus and its related complications are currently increasing. Diabetes mellitus affects the heart through various mechanisms including microvascular impairment, metabolic disturbance, subcellular component abnormalities, cardiac autonomic dysfunction, and a maladaptive immune response. Eventually, diabetes mellitus can cause functional and structural changes in the myocardium without coronary artery disease, a disorder known as diabetic cardiomyopathy (DCM). There are many diagnostic tools and management options for DCM, although it is difficult to detect its development and effectively prevent its progression. In this review, we summarize the current research regarding the pathophysiology and pathogenesis of DCM. Moreover, we discuss emerging diagnostic evaluation methods and treatment strategies for DCM, which may help our understanding of its underlying mechanisms and facilitate the identification of possible new therapeutic targets.
Topics: Cardiac Imaging Techniques; Diabetic Cardiomyopathies; Heart; Humans
PubMed: 28415836
DOI: 10.3904/kjim.2016.208 -
Acta Diabetologica Aug 2021Growing interest has been accumulated in the definition of worsening effects of diabetes in the cardiovascular system. This is associated with epidemiological data... (Review)
Review
Growing interest has been accumulated in the definition of worsening effects of diabetes in the cardiovascular system. This is associated with epidemiological data regarding the high incidence of heart failure (HF) in diabetic patients. To investigate the detrimental effects both of hyperglycemia and insulin resistance, a lot of preclinical models were developed. However, the evidence of pathogenic and histological alterations of the so-called diabetic cardiomyopathy (DCM) is still poorly understood in humans. Here, we provide a stringent literature analysis to investigate unique data regarding human DCM. This approach established that lipotoxic-related events might play a central role in the initiation and progression of human DCM. The major limitation in the acquisition of human data is due to the fact of heart specimen availability. Postmortem analysis revealed the end stage of the disease; thus, we need to gain knowledge on the pathogenic events from the early stages until cardiac fibrosis underlying the end-stage HF.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Disease Progression; Heart; Heart Failure; Humans; Hyperglycemia; Insulin Resistance; Myocardium
PubMed: 33791873
DOI: 10.1007/s00592-021-01705-x -
Advances in Experimental Medicine and... 2023Differential gene expression is associated with diabetic cardiomyopathy (DMCM) and culminates in adverse remodeling in the diabetic heart. Genome editing is a technology...
Differential gene expression is associated with diabetic cardiomyopathy (DMCM) and culminates in adverse remodeling in the diabetic heart. Genome editing is a technology utilized to alter endogenous genes. Genome editing also provides an option to induce cardioprotective genes or inhibit genes linked to adverse cardiac remodeling and thus has promise in ameliorating DMCM. Non-coding genes have emerged as novel regulators of cellular signaling and may serve as potential therapeutic targets for DMCM. Specifically, there is a widespread change in the gene expression of fetal cardiac genes and microRNAs, termed genetic reprogramming, that promotes pathological remodeling and contributes to heart failure in diabetes. This genetic reprogramming of both coding and non-coding genes varies with the progression and severity of DMCM. Thus, genetic editing provides a promising option to investigate the role of specific genes/non-coding RNAs in DMCM initiation and progression as well as developing therapeutics to mitigate cardiac remodeling and ameliorate DMCM. This chapter will summarize the research progress in genome editing and DMCM and provide future directions for utilizing genome editing as an approach to prevent and/or treat DMCM.
Topics: Humans; Diabetic Cardiomyopathies; Gene Editing; Ventricular Remodeling; Heart; Heart Failure; Diabetes Mellitus
PubMed: 36454462
DOI: 10.1007/978-981-19-5642-3_7 -
Circulation Journal : Official Journal... 2014As the link between heart failure (HF) and diabetes mellitus (DM) becomes unignorable, so the need is further increasing for pathological comprehension: What is... (Review)
Review
As the link between heart failure (HF) and diabetes mellitus (DM) becomes unignorable, so the need is further increasing for pathological comprehension: What is "diabetic cardiomyopathy (DMC)?" In response to current concern, the most updated guidelines stated by the ACCF/AHA and by the ESC/EASD take one step further, including the definition of DMC, although it is a matter yet to be completed. For more than 40 years, coronary artery disease and hypertension have been considered as the main causes of diabetes-related cardiac dysfunction. HF was originally considered as a result of reduced left ventricular ejection fraction (HF-REF); however, it has been recognized that HF symptoms are often observed in patients with preserved EF (HF-PEF). DMC includes HF with both reduced and preserved entities independent of coronary stenosis and hypertension. Cardiologists are thus facing a sort of chaos without clear guidelines for the "deadly intersection" of DM and HF. Today, the increasing interest and concern have caused DMC to be revisited and the first step in controlling the chaos around DMC is to organize and analyze all of the available evidence from preclinical and clinical studies. This review aims to illustrate the current concepts of DMC by shedding light on the new molecular mechanisms. (Circ J 2014; 78: 576-583).
Topics: Coronary Stenosis; Diabetic Cardiomyopathies; Heart Failure; Humans; Hypertension; Stroke Volume
PubMed: 24500073
DOI: 10.1253/circj.cj-13-1564 -
Cardiovascular Diabetology Aug 2023Myocardial microvascular injury is the key event in early diabetic heart disease. The injury of myocardial microvascular endothelial cells (CMECs) is the main cause and...
BACKGROUND
Myocardial microvascular injury is the key event in early diabetic heart disease. The injury of myocardial microvascular endothelial cells (CMECs) is the main cause and trigger of myocardial microvascular disease. Mitochondrial calcium homeostasis plays an important role in maintaining the normal function, survival and death of endothelial cells. Considering that mitochondrial calcium uptake 1 (MICU1) is a key molecule in mitochondrial calcium regulation, this study aimed to investigate the role of MICU1 in CMECs and explore its underlying mechanisms.
METHODS
To examine the role of endothelial MICU1 in diabetic cardiomyopathy (DCM), we used endothelial-specific MICU1 mice to establish a diabetic mouse model and evaluate the cardiac function. In addition, MICU1 overexpression was conducted by injecting adeno-associated virus 9 carrying MICU1 (AAV9-MICU1). Transcriptome sequencing technology was used to explore underlying molecular mechanisms.
RESULTS
Here, we found that MICU1 expression is decreased in CMECs of diabetic mice. Moreover, we demonstrated that endothelial cell MICU1 knockout exacerbated the levels of cardiac hypertrophy and interstitial myocardial fibrosis and led to a further reduction in left ventricular function in diabetic mice. Notably, we found that AAV9-MICU1 specifically upregulated the expression of MICU1 in CMECs of diabetic mice, which inhibited nitrification stress, inflammatory reaction, and apoptosis of the CMECs, ameliorated myocardial hypertrophy and fibrosis, and promoted cardiac function. Further mechanistic analysis suggested that MICU1 deficiency result in excessive mitochondrial calcium uptake and homeostasis imbalance which caused nitrification stress-induced endothelial damage and inflammation that disrupted myocardial microvascular endothelial barrier function and ultimately promoted DCM progression.
CONCLUSIONS
Our findings demonstrate that MICU1 expression was downregulated in the CMECs of diabetic mice. Overexpression of endothelial MICU1 reduced nitrification stress induced apoptosis and inflammation by inhibiting mitochondrial calcium uptake, which improved myocardial microvascular function and inhibited DCM progression. Our findings suggest that endothelial MICU1 is a molecular intervention target for the potential treatment of DCM.
Topics: Animals; Mice; Calcium; Calcium-Binding Proteins; Dependovirus; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Endothelial Cells; Inflammation; Mitochondrial Membrane Transport Proteins
PubMed: 37592255
DOI: 10.1186/s12933-023-01941-1 -
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 -
ESC Heart Failure Apr 2023Diabetes mellitus (DM) is a serious epidemic around the globe, and cardiovascular diseases account for the majority of deaths in patients with DM. Diabetic... (Review)
Review
Diabetes mellitus (DM) is a serious epidemic around the globe, and cardiovascular diseases account for the majority of deaths in patients with DM. Diabetic cardiomyopathy (DCM) is defined as a cardiac dysfunction derived from DM without the presence of coronary artery diseases and hypertension. Patients with either type 1 or type 2 DM are at high risk of developing DCM and even heart failure. Metabolic disorders of obesity and insulin resistance in type 2 diabetic environments result in dyslipidaemia and subsequent lipid-induced toxicity (lipotoxicity) in organs including the heart. Although various mechanisms have been proposed underlying DCM, it remains incompletely understood how lipotoxicity alters cardiac function and how DM induces clinical heart syndrome. With recent progress, we here summarize the latest discoveries on lipid-induced cardiac toxicity in diabetic hearts and discuss the underlying therapies and controversies in clinical DCM.
Topics: Humans; Diabetic Cardiomyopathies; Heart Failure; Diabetes Mellitus, Type 2; Insulin Resistance; Lipids
PubMed: 36369594
DOI: 10.1002/ehf2.14224 -
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