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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress plays a key role in the pathogenesis of diabetic cardiomyopathy, which is characterized by myocyte loss and fibrosis, finally resulting in heart failure. The study looked at the downstream signaling whereby oxidative stress leads to reduced myocardial contractility in the left ventricle of diabetic rats and the effects of dehydroepiandrosterone (DHEA), which production is suppressed in the failing heart and prevents the oxidative damage induced by hyperglycemia in several experimental models. DHEA was given orally at a dose of 4 mg/rat per day for 21 d to rats with streptozotocin (STZ)-induced diabetes and genetic diabetic-fatty (ZDF) rats. Oxidative balance, advanced glycated end products (AGEs) and AGE receptors, cardiac myogenic factors, and myosin heavy-chain gene expression were determined in the left ventricle of treated and untreated STZ-diabetic rats and ZDF rats. Oxidative stress induced by chronic hyperglycemia increased AGE and AGE receptors and led to activation of the pleoitropic transcription factor nuclear factor-kappaB. Nuclear factor-kappaB activation triggered a cascade of signaling, which finally led to the switch in the cardiac myosin heavy-chain (MHC) gene expression from the alpha-MHC isoform to the beta-MHC isoform. DHEA treatment, by preventing the activation of the oxidative pathways induced by hyperglycemia, counteracted the enhanced AGE receptor activation in the heart of STZ-diabetic rats and ZDF rats and normalized downstream signaling, thus avoiding impairment of the cardiac myogenic factors, heart autonomic nervous system and neural crest derivatives (HAND) and myogenic enhancer factor-2, and the switch in MHC gene expression, which are the early events in diabetic cardiomyopathy.
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PMID:Oxidative stress-dependent impairment of cardiac-specific transcription factors in experimental diabetes. 1693 41

This article focuses on advances in the understanding of the pathogenesis and treatment of diabetic cardiomyopathy. Patients with diabetes are at an elevated risk for heart failure, and comorbid heart failure confers an increased risk of morbidity and mortality. Diabetic cardiomyopathy and to apply proven lifesaving therapies in all heart failure patients, including those with diabetes, in the absence of contraindications or intolerance.
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PMID:Diabetic cardiomyopathy. 1695 87

Diabetes mellitus increases by 2.5 to 5 the relative risk of congestive heart failure. Besides the classical risk factors of congestive heart failure such as obesity, arterial hypertension and coronary artery disease that are frequently associated to type 2 diabetes, a diabetic cardiomyopathy plays also a role. This specific complication is related to metabolic factors and oxidative stress, leading to muscular cell apoptosis and fibrosis. The management of a diabetic patient with congestive heart failure has several specificities not only concerning the treatment of cardiac insufficiency but most importantly concerning antidiabetic therapy. The relationship between glitazones, peripheral oedema and risk of congestive heart failure is currently raising much interest and controversies.
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PMID:[Diabetes mellitus and congestive heart failure: physiopathology and treatment]. 1697 38

Doppler echocardiography has largely contributed to show the existence of a distinct diabetic cardiomyopathy. Several studies have pointed out the evidence of left ventricular (LV) remodeling and hypertrophy in alterations of both midwall systolic mechanics and LV diastolic filling in diabetes mellitus (DM), independent of the coexistence of concomitant risk factors. Further progress will be provided by new ultrasound technologies in this clinical setting. The combination of pulsed tissue Doppler study of mitral annulus with transmitral inflow may be clinically valuable for obtaining information about left ventricular filling pressure (LVFP) and unmasking Doppler inflow pseudonormal pattern, a hinge point for the progression toward advanced heart failure. In the absence of epicardial coronary artery stenosis, the ultrasound assessment of coronary flow reserve (CFR) may identify the dysfunction of coronary microcirculation, in relation with glycemic levels, insulin resistance, sympathetic overdrive, endothelial dysfunction, abnormalities of the angiotensin-renin system, and LV remodeling/hypertrophy. Diastolic dysfunction and impairment of CFR may be associated in DM, with a likely common origin. In this view, a comprehensive transthoracic Doppler evaluation of diabetic patients should include the assessment of diastolic function and estimation of LVFP by tissue Doppler, and coronary microvascular function by CFR test. Additional analysis of regional wall motion during a stress test would be required in patients with suspected coronary artery disease, another cause of diastolic dysfunction.
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PMID:Diastolic dysfunction and diabetic cardiomyopathy: evaluation by Doppler echocardiography. 1704 86

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diastolic dysfunction and heart failure in diabetes, but its molecular basis has remained obscure, in part because of its multifactorial origins. Here we employed comparative transcriptomic methods with quantitative verification of selected transcripts by reverse transcriptase quantitative PCR to characterize the molecular basis of DCM in rats with streptozotocin-induced diabetes of 16-wk duration. Diabetes caused left ventricular disease that was accompanied by significant changes in the expression of 1,614 genes, 749 of which had functions assignable by Gene Ontology classification. Genes corresponding to proteins expressed in mitochondria accounted for a disproportionate number of those whose expression was significantly modified in DCM, consistent with the idea that the mitochondrion is a key target of the pathogenic processes that cause myocardial disease in diabetes. Diabetes also induced global perturbations in the expression of genes regulating cardiac fatty acid metabolism, whose dysfunction is likely to play a key role in the promotion of oxidative stress, thereby contributing to the pathogenesis of diabetic myocardial disease. In particular, these data point to impaired regulation of mitochondrial beta-oxidation as central in the mechanisms that generate DCM pathogenesis. This study provides a comprehensive molecular snapshot of the processes leading to myocardial disease in diabetes.
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PMID:Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease. 1706 50

Individuals with diabetes mellitus have an increased risk of developing heart failure, usually as a consequence of coronary artery disease, although a specific diabetic cardiomyopathy, secondary to a microangiopathy, may also exist. The thiazolidinediones, a relatively new class of insulin-sensitizing agents used in the management of type 2 diabetes mellitus, have a number of complex metabolic actions on surrogate markers of atherogenesis, supported by the results of the recently published PROACTIVE (PROspective pioglitAzone Clinical Trial In macroVascular Events) trial. Unfortunately, the use of thiazolidinediones in individuals with diabetes mellitus and heart failure is limited because of a propensity to cause fluid retention. The underlying mechanisms of fluid retention have yet to be fully elucidated, but appear to be a dose-related class effect, exacerbated by combination therapy with insulin, and in some cases may be localized to peripheral edema. In parallel, echocardiographic studies show no significant effect of thiazolidinediones on cardiac structure or function. The design of epidemiologic studies describing an increased risk of developing heart failure in individuals with type 2 diabetes mellitus prescribed thiazolidinediones has been questioned, and a study of 'new users' of antihyperglycemic treatments found no increased risk of hospitalization for heart failure with thiazolidinedione therapy. There is also increasing evidence for the potential benefits of insulin sensitization in patients with diabetes mellitus and known heart failure, and a large observational study of over 16 000 patients with a principal discharge diagnosis of heart failure found a reduced mortality (hazard ratio [HR] 0.87; 95% CI 0.80, 0.94) in those prescribed thiazolidinediones. This benefit was offset by an increased risk of readmission with heart failure (HR 1.06; 95% CI 1.00, 1.09). Despite an increase in fluid-related events, recent studies suggest that individuals with type 2 diabetes mellitus and heart failure (New York Heart Association grade I/II) can be treated with thiazolidinediones with appropriate monitoring and adjustment of heart failure therapies. These findings would suggest the need for large-scale, prospective trials to investigate the safety and potential benefits of thiazolidinedione use in patients with diabetes mellitus and heart failure.
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PMID:Thiazolidinediones in patients with diabetes mellitus and heart failure : implications of emerging data. 1708 64

Diabetic cardiomyopathy has been documented as an underlying etiology of heart failure (HF) among diabetics. Although oxidative stress has been proposed to contribute to diabetic cardiomyopathy, much of the evidence lacks specificity. Furthermore, whether alterations occur at the cardiac proteome level in diabetic cardiac complications with attendant oxidative stress remains unknown. Therefore, we sought to identify cardiac protein changes in relation to myocardial oxidative stress that are specific to diabetic cardiomyopathy. Diabetes was induced in rats by a single injection of streptozotocin (STZ). STZ-treated rats were examined for diabetic cardiomyopathy at 8 weeks post-STZ by left ventricular (LV) hemodynamic analysis. LV systolic pressure (LVSP), rate of pressure rise (+dP/dt), and rate of pressure decay (-dP/dt) were depressed while LV end-diastolic pressure (LVEDP) was increased. Myocardial oxidative stress was increased in STZ-diabetic rats, as indexed by significant increases in myocardial formation of 8-iso PGF(2alpha) and oxidized glutathione (GSSG). In-depth mining of the diabetic myocardial proteome by proteomic analysis utilizing two-dimensional difference gel electrophoresis and mass spectrometry (DIGE/MS) techniques revealed that a high proportion (12 of 24) of the altered proteins that could be identified by mass spectrometry were localized to the mitochondria. Down-regulation of antioxidant and anti-apoptotic proteins was also observed in STZ-diabetic hearts. These results characterize a specific 'type I diabetic' pattern of cardiac proteome changes indicative of diabetic cardiomyopathy presenting with higher oxidative stress, supporting the idea that analysis of isoprostane biosynthesis and protein expression profiles may be useful diagnostically to assess the efficacy of antioxidant therapies as prophylactic treatments against type I diabetes mellitus complications involving the heart.
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PMID:Alterations in the diabetic myocardial proteome coupled with increased myocardial oxidative stress underlies diabetic cardiomyopathy. 1732 Jan

We investigated the effect of the angiotensin type 1 (AT-1) receptor antagonist, irbesartan, on matrix metalloproteinase (MMP) activity and cardiac cytokines in an animal model of diabetic cardiomyopathy. Diabetes was induced in 20 C57/bl6 mice by injection of streptozotocin (STZ). These animals were treated with irbesartan or placebo and were compared with nondiabetic controls. Left ventricular (LV) function was measured by pressure-volume loops with parameters for systolic function (end systolic elastance [Ees]) and diastolic function (cardiac stiffness) 8 weeks after STZ treatment. The cardiac protein content of interleukin (IL)1beta and transforming growth factor (TGF)beta1 were measured by enzyme-linked immunosorbent assay. The total cardiac collagen content and collagen type 1 and 3 were measured by histochemistry, and MMP-2 activity was measured by gelatin zymography. LV dysfunction was documented by impaired Ees and diastolic stiffness in STZ mice compared with controls. This was accompanied by increased TGFbeta, IL1beta, and fibrosis and decreased MMP-2 activity. Treatment with irbesartan attenuated LV dysfunction, IL1beta, TGFbeta, and cardiac fibrosis compared with untreated diabetic animals and normalized MMP activity. These findings present evidence that AT-1 receptor antagonists attenuate cardiac failure by decreasing cardiac inflammation and normalizing MMP activity, leading to normalized cardiac fibrosis in STZ-induced diabetic cardiomyopathy.
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PMID:Contributions of inflammation and cardiac matrix metalloproteinase activity to cardiac failure in diabetic cardiomyopathy: the role of angiotensin type 1 receptor antagonism. 1732 31

Despite the significant developments in the treatment of diabetes mellitus, diabetic patients still continue to suffer from cardiac complications. The increase of cardiac adrenergic drive may ultimately contribute to the development and progression of diabetic cardiomyopathy. beta-Adrenoceptors play an important role in the regulation of heart function. However, responsiveness of diabetic heart to beta-adrenoceptor agonist stimulation is diminished. The chronotropic responses mediated by beta(1)-subtype, which is mainly responsible for cardiac effects of catecholamines are decreased in the atria of diabetic rats. The expression of cardiac beta(1)-subtype is significantly decreased in diabetic rats as well. beta(2)-Adrenoceptors also increase cardiac function. Although the expression of this subtype is slightly decreased in diabetic rat hearts, beta(2)-mediated chronotropic responses are preserved. On the other hand, functional beta(3)-adrenoceptor subtype was characterized in human heart. Interestingly, stimulation of cardiac beta(3)-adrenoceptors, on the contrary of beta(1)- and beta(2)-subtypes, mediates negative inotropic effect in human ventricular muscle. Cardiac beta(3)-adrenoceptors are upregulated in experimental diabetes as well as in human heart failure. These findings suggest that each beta-adrenoceptor subtype may play an important role in the pathophysiology of diabetes-induced heart disease. However, it is still not known whether the changes in the expression and/or responsiveness of beta-adrenoceptors are adaptive or maladaptive. Therefore, this review outlines the potential roles of these receptor subtypes in cardiac pathologies of diabetes.
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PMID:The influence of diabetes on cardiac beta-adrenoceptor subtypes. 1736 27

Epidemiological and clinical studies show a clear association of diabetes mellitus with congestive heart failure and cardiovascular events independent of blood pressure and ischemic heart disease. The definition of 'diabetic cardiomyopathy' as a clinical entity, however, relies on distinct myocellular and interstitial alterations found in the myocardium of patients with diabetes. The histological findings comprise myocellular hypertrophy, thickening of capillary basement membranes, interstitial fibrosis and rarification of mitochondria on the ultrastructural level. For clinical routine, early detection of diabetic cardiomyopathy seems crucial for identification of patients at cardiovascular risk since the prevalence of heart failure in individuals with diabetes is markedly increased. Recent technical developments in cardiac magnetic resonance imaging (MRI), echocardiography as well as nuclear scintigraphy have advanced the diagnostic applications for the detection of diabetic heart disease. This review aims to present distinct aspects of diabetic cardiomyopathy that were identified using non- invasive imaging techniques. Due to the wide availability and the low costs of echocardiography, it is the most frequently used imaging technique to detect left ventricular dysfunction in patients with diabetes. MRI on the other hand can provide assessment of myocardial structure with higher spatial resolution and allows objective assessment of left ventricular function. This makes MRI an attractive alternative for the detection of discrete alterations, particularly in patients with poor echogenic windows. Finally, nuclear scintigraphy can provide information on cardiac autonomic integrity and accurately detect defects in autonomic control, which are considered a major cardiovascular risk factor in patients with diabetes.
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PMID:Non-invasive diagnostic imaging techniques as a window into the diabetic heart: a review of experimental and clinical data. 1747 36


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