Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 1 and type 2 diabetic patients are at increased risk of cardiomyopathy and heart failure is a major cause of death for these patients. Cardiomyopathy in diabetes is associated with a cluster of features including decreased diastolic compliance, interstitial fibrosis and myocyte hypertrophy. The mechanisms leading to diabetic cardiomyopathy remain uncertain. Diabetes is associated with most known risk factors for cardiac failure seen in the overall population, including obesity, dyslipidemia, thrombosis, infarction, hypertension, activation of multiple hormone and cytokine systems, autonomic neuropathy, endothelial dysfunction and coronary artery disease. In light of these common contributing pathologies it remains uncertain whether diabetic cardiomyopathy is a distinct disease. It is also uncertain which factors are most important to the overall incidence of heart failure in diabetic patients. This review focuses on factors that can have direct effects on diabetic cardiomyocytes: hyperglycemia, altered fuel use, and changes in the activity of insulin and angiotensin. Particular attention is given to the changes these factors can have on cardiac mitochondria and the role of reactive oxygen species in mediating injury to cardiomyocytes.
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PMID:Causes and characteristics of diabetic cardiomyopathy. 1748 34

Diabetic cardiomyopathy is a myocardial disease caused by diabetes mellitus unrelated to vascular and valvular pathology or systemic arterial hypertension. Clinical and experimental studies have shown that diabetes mellitus causes myocardial hypertrophy, necrosis, and apoptosis, and increases interstitial tissue. The pathophysiology of diabetic cardiomyopathy is incompletely understood. It appears that metabolic perturbations such as hyperlipidemia, hyperinsulinemia, hyperglycemia, and changes in cardiac metabolism are involved in cellular consequences leading to increased oxidative stress, interstitial fibrosis, myocyte death, and altered intracellular ions transient and calcium homeostasis. Clinically, an early detection of asymptomatic diastolic dysfunction is possible. When patients develop signals and symptoms of heart failure, isolated diastolic dysfunction is usually detected. Systolic dysfunction is a late finding. Treatment of heart failure due to diabetic cardiomyopathy is not different from myocardiopathies of other etiologies and must follow the guidelines according to ventricular function, whether diastolic or diastolic and systolic impairment.
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PMID:[Diabetic cardiomyopathy]. 1750 22

Diabetes mellitus, a disease that has been reaching epidemic proportions, is an important risk factor to the development of cardiovascular complication. Diabetes causes changes within the cardiac structure and function, even in the absence of atherosclerotic disease. The left ventricular diastolic dysfunction (VE) represents the earliest pre-clinical manifestation of diabetic cardiomyopathy, preceding the systolic dysfunction and being able to evolve to symptomatic heart failure. The doppler echocardiography has emerged as an important noninvasive diagnostic tool, providing reliable data in the stages of diastolic function, as well as for systolic function. With the advent of recent echocardiographic techniques, such as tissue Doppler and color M-mode, the accuracy in identifying the moderate diastolic dysfunction, the pseudonormal pattern, has significantly improved. Due to cardio-metabolic repercussions of DM, a detailed evaluation of cardiovascular function in diabetic patients is important, and some alterations may be seen even in patients with gestational diabetes.
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PMID:Left ventricle diastolic dysfunction in diabetes: an update. 1750 23

Cardiac failure is a leading cause for the mortality of diabetic patients, in part due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy, which occurs with or without co-existence of vascular diseases. Although several mechanisms responsible for diabetic cardiomyopathy have been proposed, oxidative stress is widely considered as one of the major causes for the pathogenesis of the disease. Thus, a few laboratories are trying to develop antioxidants used to prevent diabetic cardiomyopathy. Metallothioneins (MTs) are cysteine-rich metal-binding proteins with several biological roles including antioxidant property. We and others have indicated the significant cardiac protection of MT against diabetes using cardiac-specific MT-overexpressing transgenic mice and OVE26MT mice (cross-bred of cardiac MT transgenic mice with genetically engineered diabetic OVE26 mice). Several possible mechanisms responsible for MT's cardiac protection from diabetes were revealed. These include MT's important roles in calcium regulation, zinc homeostasis, insulin sensitization, and antioxidant action. Since MT is ubiquitously expressed in mammalian tissues and is highly inducible by a variety of reagents such as zinc, the clinical potential for inducing cardiac MT as an antioxidant by zinc supplementation to prevent various diabetic complications, including cardiomyopathy, has been explored in diabetic animal models and patients. Since zinc has been therapeutically used for several other non-diabetic diseases in clinics, it provides further potential use of zinc for diabetic patients. Therefore, this review will briefly introduce the biochemical features of MT along with its critical roles in redox homeostasis and antioxidant function in the heart, and then discuss the current research on the prevention of diabetic cardiomyopathy by MT with an emphasis on experimental evidence, possible mechanisms, and clinical implications.
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PMID:Diabetic cardiomyopathy and its prevention by metallothionein: experimental evidence, possible mechanisms and clinical implications. 1769 57

Heart failure (HF) is a major contributor to poor quality of life, a leading cause of hospitalization, and cause of premature death. Both kidney disease and diabetes are major and independent risk factors for the development of heart failure, such that individuals with diabetic nephropathy are at especially high risk. Such patients not only are likely to have coronary artery disease and hypertension but also are likely to have diabetic cardiomyopathy, a distinct pathologic entity that is more closely associated with the microvascular than the macrovascular complications of diabetes. In addition to a better understanding of the epidemiology of HF, advances in noninvasive imaging have highlighted the importance of early cardiac dysfunction in diabetes and the high prevalence of HF with preserved left ventricular systolic function. Although significant renal dysfunction is usually an exclusion criterion in HF trials, diabetes is often a prespecified subgroup so that subanalyses of large multicenter clinical trials do provide some guidance in therapeutic decision-making. However, further therapies for both HF and nephropathy in diabetes clearly are needed, and a number of new therapeutic strategies that target both disorders have already entered the clinical arena.
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PMID:Heart failure and nephropathy: catastrophic and interrelated complications of diabetes. 1769 8

Ceramide, a sphingolipid metabolite, has emerged as a key second messenger molecule that mediates multiple cellular functions. Its de nova synthesis and accumulation in ischemic myocardium, congestive heart failure and diabetic cardiomyopathy is associated with the abnormalities such as abnormal QT prolongation and increased risk of arrhythmias. To investigate how ceramide is involved in modulating cardiac repolarization, we performed whole-cell patch-clamp studies on HERG current (I(HERG)), a critical determinant of cardiac repolarization, expressed in HEK293 cells. Acute application (superfusion for 25 min) of membrane permeable ceramide (C2, 5 microM) did not alter I(HERG). Prolonged incubation with C2 for 10 hrs caused pronounced I(HERG) inhibition in a concentration-dependent and voltage-independent fashion and positive shift of voltage-dependent HERG activation. The IC(50) for I(HERG) suppression was 19.5 microM. C2 did not affect the inactivation property and time-dependent kinetics of I(HERG). Similar effects were observed with production of endogenous ceramide catalyzed by sphingomyelinase. Tyrosine kinase inhibitors failed to reverse C2-induced suppression of HERG function, and PKA and PKC inhibitors only slightly reversed the I(HERG) depression. Western blotting and immunocytochemical analyses indicate that C2 does not alter HERG protein expression on the cytoplasmic membrane. The inhibitory effect of C2 on I(HERG) was reversed by antioxidants vitamin E or MnTBAP. C2 caused considerable production of intracellular reactive oxygen species (ROS), which was prevented by vitamin E or MnTBAP. We conclude that ceramide depresses I(HERG) mainly via ROS overproduction and ceramide-induced I(HERG) impairment may contribute to QT prolongation in prolonged myocardial ischemia, heart failure and diabetic cardiomyopathy.
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PMID:Sphingolipid metabolite ceramide causes metabolic perturbation contributing to HERG K+ channel dysfunction. 1776 70

Type 2 diabetes and heart failure commonly occur together and this combination is associated with poor outcomes. The relationship is likely to be multifactorial and also may involve a specific, though ill-defined, diabetic cardiomyopathy. Glucose-lowering therapies may also be associated with an increased risk of heart failure. Data from recent large-scale clinical trials have drawn particular attention to the thiazolidinediones that appear to increase the risk of heart failure in patients with type 2 diabetes. Although pioglitazone therapy has been shown to decrease the risk of macrovascular events, the overall cardiovascular benefit needs to be addressed together with the apparent increase in heart failure risk. In this review, we provide appropriate context for assessing this balance from several perspectives. First, we consider the high underlying risk of heart failure already present in type 2 diabetes. Secondly, we highlight a potential distinction between genuine heart failure due to cardiac dysfunction and thiazolidinedione-associated oedema that may simply unmask previously undiagnosed cardiac dysfunction without itself having any direct impact on heart muscle. Most importantly, we emphasize the apparent lack of any long-term mortality consequences and a relative improvement in outcomes associated with thiazolidinedione-induced 'heart failure' and discuss the potential mechanisms underlying this apparent paradox. Finally, we review the current guidelines for thiazolidinedione use and heart failure and suggest potential future strategies for avoiding and/or minimizing this association.
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PMID:Weighing up the cardiovascular benefits of thiazolidinedione therapy: the impact of increased risk of heart failure. 1851 Apr 80

Obesity is a well-known risk factor for the development of type 2 diabetes mellitus and cardiovascular disease. Importantly, obesity is not only associated with lipid accumulation in adipose tissue, but also in non-adipose tissues. The latter is also known as ectopic lipid accumulation and may be a possible link between obesity and its comorbidities such as insulin resistance, type 2 diabetes mellitus and cardiovascular disease. In skeletal muscle and liver, lipid accumulation has been associated with the development of insulin resistance, an early hallmark of developing type 2 diabetes mellitus. More specifically, accumulation of intermediates of lipid metabolism, such as diacylglycerol (DAG) and Acyl-CoA have been shown to interfere with insulin signaling in these tissues. Initially, muscular and hepatic insulin resistance can be overcome by an increased insulin production by the pancreas, resulting in hyperinsulinemia. However, during the progression towards overt type 2 diabetes, pancreatic failure occurs resulting in reduced insulin production. Interestingly, also in the pancreas lipid accumulation has been shown to precede dysfunction. Finally, accumulation of fat in the heart has been associated with cardiac dysfunction and heart failure, which may be an explanation for diabetic cardiomyopathy. Taken together, we conclude that evidence for deleterious effects of lipid accumulation in non-adipose tissue (lipotoxicity) is strong. However, while ample human data is available for skeletal muscle and the liver, future research should focus on lipid accumulation in the pancreas and the heart.
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PMID:Lipid accumulation in non-adipose tissue and lipotoxicity. 1822 98

Independent of the severity of coronary artery disease, diabetic patients have an increased risk of developing heart failure. Diabetic cardiomyopathy (DCM) is characterized by microvascular pathologies and interstitial fibrosis. Mesenchymal stem cells (MSCs) are pluripotent and are able to differentiate into cardiomyocytes and vascular endothelial cells. Studies have demonstrated MSCs transplantation can prevent apoptosis of ischemic heart via upregulation of Akt and eNOS and inhibit myocardial fibrosis of dilated cardiomyopathy by decreasing the expression of matrix metalloproteinase (MMP) in rat models. In order to find out whether transplantation of MSCs is a promising treatment in DCM, we used streptozotocin (STZ) -induced diabetic rats as the model. Exogenous MSCs were injected into the femoral vein 8 weeks after STZ injection. Using independent experimental approaches, we showed that MSCs presented in the myocardium 4 weeks after transplantation and some of them were positive for the cardiac markers Troponin T and myosin heavy chain. MSCs transplantation significantly increased myocardial arteriolar density and decreased the collagen volume in diabetic myocardium resulting in improved cardiac function. Furthermore, MSCs transplantation increased MMP-2 activity and decreased transcriptional level of MMP-9. These results show that MSCs transplantation improved cardiac function in the rat DCM model, possibly through angiogenesis and attenuation of cardiac remodeling.
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PMID:Bone marrow mesenchymal stem cells induce angiogenesis and attenuate the remodeling of diabetic cardiomyopathy. 1828 26

Apoptosis plays a critical role in the diabetic cardiomyopathy, and endoplasmic reticulum stress (ERS) is one of the intrinsic apoptosis pathways. Previous studies have shown that the endoplasmic reticulum becomes swollen and dilated in diabetic myocardium, and ERS is involved in heart failure and diabetic kidney. This study is aimed to demonstrate whether ERS is induced in myocardium of streptozotocin (STZ)-induced diabetic rats. We established a type 1 diabetic rat model, used echocardiographic evaluation, hematoxylin-eosin staining, and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling staining to identify the existence of diabetic cardiomyopathy and enhanced apoptosis in the diabetic heart. We performed immunohistochemistry, western blot, and real-time PCR to analyze the hallmarks of ERS that include glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase12. We found these hallmarks to have enhanced expression in protein and mRNA levels in diabetic myocardium. Also, another pathway that can lead to cell death of ERS, c-Jun NH(2)-terminal kinase-dependent pathway, was also activated in diabetic heart. Those results suggested that ERS was induced in STZ-induced diabetic rats' myocardium, and ERS-associated apoptosis occurred in the pathophysiology of diabetic cardiomyopathy.
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PMID:Endoplasmic reticulum stress is involved in myocardial apoptosis of streptozocin-induced diabetic rats. 2084 65


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