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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The phospholipases associated with the cardiac sarcolemmal (SL) membrane hydrolyze specific membrane phospholipids to generate important lipid signaling molecules, which are known to influence normal cardiac function. However, impairment of the phospholipases and their related signaling events may be contributory factors in altering cardiac function of the diseased myocardium. The identification of the changes in such signaling systems as well as understanding the contribution of phospholipid-signaling pathways to the pathophysiology of heart disease are rapidly emerging areas of research in this field. In this paper, I provide an overview of the role of phospholipid-mediated signal transduction processes in cardiac hypertrophy and congestive heart failure, diabetic cardiomyopathy, as well as in ischemia-reperfusion. From the cumulative evidence presented, it is suggested that phospholipid-mediated signal transduction processes could serve as novel targets for the treatment of the different types of heart disease.
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PMID:Phospholipid-mediated signaling systems as novel targets for treatment of heart disease. 1748 43

Oxidative stress has been widely recognized to be involved in the pathogenesis of cardiopulmonary disorders. In ischemic heart diseases, it is involved not only in the development of atherosclerosis but also in ongoing ischemic injury, especially in the reperfusion process. Cardiomyopathy is another cardiac disorder in which oxidative stress is involved. In diabetic cardiomyopathy, homocysteine, a well-known source of oxidative stress, is believed to play major roles in its development. Thioredoxin (TRX) is a redox-acting protein ubiquitously present in the human body. It also is inducible by a wide variety of oxidative stresses. TRX is a multifunctional protein and has anti-inflammatory and antiapoptotic effects, as well as antioxidative effects. It is therefore feasible to think that TRX is a potential therapy for cardiac disease. Moreover, serum TRX is a well-recognized biomarker of various diseases involving oxidative stress, and this is also the case for cardiac disorders. Here we discuss how TRX is useful as a biomarker of and therapeutic agent for cardiopulmonary disorders, especially focusing on ischemic heart disease, myocarditis and oxygen sensing, and acute respiratory distress syndrome.
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PMID:From oxygen sensing to heart failure: role of thioredoxin. 1751 84

Heart disease is the leading cause of death in patients with insulin resistance and type 2 diabetes (DM2). Even in the absence of coronary artery disease and hypertension, functional and structural abnormalities exist in patients with well-controlled and uncomplicated DM2. These derangements are collectively designated by the term diabetic cardiomyopathy (DCM). Changes in myocardial energy metabolism, due to altered substrate supply and utilization, largely underlie the development of DCM. Insulin is an important regulator of myocardial substrate metabolism, but also exerts regulatory effects on intracellular Ca2+ handling and cell survival. The current paper reviews the multiple functional and molecular effects of insulin on the heart, all of which ultimately seem to be cardioprotective both under normal conditions and under ischemia. In particular, the dismal consequences of myocardial insulin resistance contributing to the development of DCM will be discussed.
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PMID:Myocardial insulin action and the contribution of insulin resistance to the pathogenesis of diabetic cardiomyopathy. 1755 6

Cardiovascular disease is the leading cause of death among patients with Type 2 diabetes mellitus. The main forms of structural heart disease associated with diabetes are coronary heart disease and diabetic cardiomyopathy, which is characterized by left ventricular hypertrophy, left ventricular diastolic and systolic dysfunction. Asymptomatic structural heart disease is common and associated with a poor prognosis in patients with diabetes. Contemporary practice guidelines do not recommend screening of asymptomatic individuals for structural heart disease. Potential screening modalities, such as echocardiography, are costly and inaccessible. A simple, inexpensive blood test for brain natriuretic peptide is a useful marker of structural heart disease and is a prime candidate for screening patients with Type 2 diabetes mellitus and prioritizing referral for echocardiography.
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PMID:Early detection and significance of structural cardiovascular abnormalities in patients with Type 2 diabetes mellitus. 1809 11

Cardiac hypertrophy, congestive heart failure, diabetic cardiomyopathy and myocardial ischemia-reperfusion injury are associated with a disturbance in cardiac sarcolemmal membrane phospholipid homeostasis. The contribution of the different phospholipases and their related signaling mechanisms to altered function of the diseased myocardium is not completely understood. Resolution of this issue is essential for both the understanding of the pathophysiology of heart disease and for determining if components of the phospholipid signaling pathways could serve as appropriate therapeutic targets. This review provides an outline of the role of phospholipase A2, C and D and subsequent signal transduction mechanisms in different cardiac pathologies with a discussion of their potential as targets for drug development for the prevention/treatment of heart disease.
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PMID:Phospholipid-mediated signaling and heart disease. 1875 16

Cell-based myocardial regenerative therapy is undergoing experimental and clinical trials in order to limit the consequences of decreased contractile function and compliance of damaged ventricles owing to ischemic and nonischemic myocardial diseases. A variety of myogenic and angiogenic cell types have been proposed, such as skeletal myoblasts, mononuclear and mesenchymal bone marrow cells, circulating blood-derived progenitors, adipose-derived stromal cells, induced pluripotent stem cells, umbilical cord cells, endometrial mesenchymal stem cells, adult testis pluripotent stem cells and embryonic cells. Current indications for stem cell therapy concern patients who have had a left- or right-ventricular infarction or idiopathic dilated cardiomyopathies. Other indications and potential applications include patients with diabetic cardiomyopathy, Chagas heart disease (American trypanosomiasis), ischemic mitral regurgitation, left ventricular noncompacted myocardium and pediatric cardiomyopathy. Suitable sources of cells for cardiac implant will depend on the types of diseases to be treated. For acute myocardial infarction, a cell that reduces myocardial necrosis and augments vascular blood flow will be desirable. For heart failure, cells that replace or promote myogenesis, reverse apoptopic mechanisms and reactivate dormant cell processes will be useful. It is important to note that stem cells are not an alternative to heart transplantation; selected patients should be in an early stage of heart failure as the goal of this regenerative approach is to avoid or delay organ transplantation. Since the cell niche provides crucial support needed for stem cell maintenance, the most interesting and realistic perspectives include the association of intramyocardial cell transplantation with tissue-engineered scaffolds and multisite cardiac pacing in order to transform a passive regenerative approach into a 'dynamic cellular support', a promising method for the creation of 'bioartificial myocardium'.
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PMID:Cellular cardiac regenerative therapy in which patients? 1967 69

Diabetic cardiomyopathy increases the risk of heart failure in individuals with diabetes, independently of co-existing coronary artery disease and hypertension. The underlying mechanisms for this cardiac complication are incompletely understood. Research on rodent models of type 1 and type 2 diabetes, and the use of genetic engineering techniques in mice, have greatly advanced our understanding of the molecular mechanisms responsible for human diabetic cardiomyopathy. The adaptation of experimental techniques for the investigation of cardiac physiology in mice now allows comprehensive characterization of these models. The focus of the present review will be to discuss selected rodent models that have proven to be useful in studying the underlying mechanisms of human diabetic cardiomyopathy, and to provide an overview of the characteristics of these models for the growing number of investigators who seek to understand the pathology of diabetes-related heart disease.
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PMID:Rodent models of diabetic cardiomyopathy. 1972 5

Isoform-switching of the giant elastic protein titin is a main mechanism for adjusting passive myocardial stiffness in perinatal heart development and chronic heart disease. Previous evidence suggested that thyroid-hormone signaling converging onto the phosphoinositol-3-kinase (PI3K)/AKT pathway regulates titin-isoform composition in developing cardiomyocytes. Here we hypothesized that insulin, another activator of PI3K/AKT, alters titin-isoform composition and titin-based stiffness. We also checked for insulin-induced changes in titin phosphorylation. In embryonic rat cardiomyocytes cultured in the presence of insulin for 7 days, the mean proportion of the stiff N2B-titin isoform (M(w), 3000 kDa) significantly increased from 53% in controls to 65% in insulin-treated cells, the remainder being the more compliant N2BA-isoforms (M(w), 3200-3700 kDa). This insulin-dependent titin-isoform shift was blocked by PI3K-inhibitor, LY294002, suggesting that insulin controls the cardiac titin-isoform pattern by activating PI3K/AKT. Titin phosphorylation was substantially increased in insulin-treated compared to control cardiomyocytes. The impact of insulin-deficiency in vivo on titin-isoform expression, titin phosphorylation, and passive myocardial stiffness was studied in streptozotocin-treated (STZ) rats as a model of diabetes mellitus type-1. Within 5 months, STZ rats developed cardiac hypertrophy and mild left ventricular fibrosis, concomitant with elevated glucose levels. The mean proportion of N2B-titin was slightly but significantly decreased from 86% in controls to 79% in STZ hearts. Titin phosphorylation levels remained unchanged. Mechanical measurements on skinned cardiac fibers showed only minor passive stiffness modifications in STZ myocardium. We conclude that insulin signaling regulates titin-isoform composition and titin phosphorylation in embryonic cardiomyocytes and could also contribute to altered diastolic function in diabetic cardiomyopathy.
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PMID:Insulin signaling regulates cardiac titin properties in heart development and diabetic cardiomyopathy. 2018 88

Cardiac disease is the commonest cause of death amongst diabetic patients. Diabetic cardiomyopathy, which has a poor prognosis, is characterized by left ventricular hypertrophy and impaired cardiac function and mitochondrial damage is said to contribute to its development. We recently showed that treatment with the Cu(II) -selective chelator, triethylenetetramine (TETA), improved cardiac structure, and function in diabetic subjects without modifying hyperglycemia. Thus, TETA has potential utility for the treatment of heart disease. To further understand the molecular mechanism by which it causes these effects, we have conducted the first study of the effect of oral TETA on protein abundance in the cardiac left ventricle of rats with severe streptozotocin-induced diabetes. Proteomic methods showed that of 211 proteins changed in diabetes, 33 recovered after treatment. Through MS, 16 proteins were identified which may constitute major targets of drug action. Remarkably, most of these were mitochondrial proteins with roles in energy metabolism. In addition to components of the mitochondrial respiratory chain and enzymes involved in fatty acid oxidation, TETA treatment normalized both myocardial expression and enzymatic activity of carnitine palmitoyltransferase 2. These findings indicate that mitochondria constitute major targets in the mechanism by which TETA restores cardiac structure and function in diabetes.
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PMID:Reversal of diabetes-evoked changes in mitochondrial protein expression of cardiac left ventricle by treatment with a copper(II)-selective chelator. 2113 91


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