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)

Accumulation of oxidized-matrix between the endothelium and myocytes is associated with endocardial endothelial (EE) dysfunction in diabetes and heart failure. High levels of circulating homocysteine (Hcy) have been demonstrated in diabetes mellitus (DM). These high levels of Hcy (hyperhomocysteinemia, HHcy) have a negative correlation with peroxisome proliferator activated receptor (PPAR) expression. Studies have demonstrated that Hcy decreases bioavailability of endothelial nitric oxide (eNO), generates nitrotyrosine, and activates latent matrix metalloproteinase (MMP), instigating EE dysfunction. PPAR ligands ameliorate endothelial dysfunction and DM. In addition Hcy competes with PPAR ligands. The understanding of molecular, cellular, and extracellular mechanisms by which Hcy amplifies DM will have therapeutic ramifications for diabetic cardiomyopathy.
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PMID:Role of nitric oxide in matrix remodeling in diabetes and heart failure. 1265 56

There is a high frequency of heart failure (HF) accompanied by an increased mortality risk for patients with diabetes. The poor prognosis of these patients has been explained by an underlying diabetic cardiomyopathy exacerbated by hypertension and ischemic heart disease. In these patients, activation of the sympathetic nervous system results in increased myocardial utilization of fatty acids and induction of fetal gene programs, decreasing myocardial function. Activation of the renin-angiotensin system results in myocardial remodeling. It is imperative for physicians to intercede early to stop the progression of HF, yet at least half of patients with left ventricular dysfunction remain undiagnosed and untreated until advanced disease causes disability. This delay is largely because of the asymptomatic nature of early HF, which necessitates more aggressive assessment of HF risk factors and early clinical signs. Utilization of beta-blockade, ACE inhibitors, or possibly angiotensin receptor blockers is essential in preventing remodeling with its associated decline in ventricular function. beta-Blockers not only prevent, but may also reverse, cardiac remodeling. Glycemic control may also play an important role in the therapy of diabetic HF. The adverse metabolic side effects that have been associated with beta-adrenergic inhibitors in the diabetic patient may be circumvented by use of a third-generation beta-blocker. Prophylactic utilization of ACE inhibitors and beta-blockers to avoid, rather than await, the need to treat HF should be considered in high-risk diabetic patients.
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PMID:Heart failure: the frequent, forgotten, and often fatal complication of diabetes. 1288 75

In many types of heart failure cardiac myocyte Ca(2+) handling is abnormal because of downregulation of key Ca(2+) - handling proteins like sarco(endo)plasmic reticulum Ca(2+) - ATPase (SERCA)2a and ryanodine receptor (RyR)2. The alteration in SERCA2a and RyR2 expression results in altered cytosolic Ca(2+) transients, leading to abnormal contraction. Sorcin is an EF-hand protein that confers the property of caffeine-activated intracellular Ca(2+) release in nonmuscle cells by interacting with RyR2. To determine whether sorcin could improve the contractile function of the heart, we overexpressed sorcin in the heart of either normal or diabetic mice and in adult rat cardiomyocytes with an adenoviral gene transfer approach. Sorcin overexpression was associated with an increase in cardiac contractility of the normal heart and dramatically rescued the abnormal contractile function of the diabetic heart. These effects could be attributed to an improvement of the Ca(2+) transients found in the cardiomyocyte after sorcin overexpression. Viral vector-mediated delivery of sorcin to cardiac myocytes is beneficial, resulting in improved contractile function in diabetic cardiomyopathy.
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PMID:In vivo adenoviral transfer of sorcin reverses cardiac contractile abnormalities of diabetic cardiomyopathy. 1295 30

The risk for cardiovascular disease, particularly congestive heart failure, is significantly higher in patients with type 2 diabetes mellitus than in individuals without diabetes. The presence of hyperglycemia has been associated with changes in the myocardium that are characteristic of diabetic cardiomyopathy and heart failure. Furthermore, insulin resistance may be associated with cardiomyopathy, even in the absence of hyperglycemia, and has been linked with cardiovascular remodeling. The association between heart failure and insulin resistance suggests that agents that improve insulin sensitivity, such as the thiazolidinediones (TZDs), are likely to be of cardiovascular benefit in patients with diabetes and heart failure. Although TZDs have beneficial cardiovascular effects in patients with type 2 diabetes, such as reducing blood pressure, improving endothelial function, and exerting potential antiatherosclerotic effects, one must be aware of the potential of these agents to cause edema or weight gain as a result of fluid retention and fat accumulation. These issues are of particular concern in patients with diabetes who have heart failure. However, the glycemic and cardiovascular benefits of TZDs may outweigh the potential problems of weight gain and fluid retention noted in some patients. Thus the risk-benefit ratio of using TZDs in patients who have diabetes and heart failure must be carefully considered in this patient population with comorbid disorders.
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PMID:The patient with diabetes mellitus and heart failure: at-risk issues. 1467 75

Heart failure is known to be a complication of insulin-dependent (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) even in the absence of coronary heart disease or hypertension. The mechanisms leading to diabetic cardiomyopathy are unknown. The aim of the study was to characterize structural and functional alterations in hyperinsulinemic Zucker diabetic fatty (ZDF) rats treated with or without insulin. Diabetic animals showed a twofold increase in cardiomyocyte volume with increased left ventricular ANP but not BNP mRNA levels in spite of a reduced plasma renin activity (PRA) 2 months after onset of diabetes compared to nondiabetic littermates. These changes were associated with an increase in left ventricular performance as assessed by echocardiography. Insulin treatment led to a significant increase in body weight (BW), total heart weight, myocardial protein content, and left ventricular mass (LVM). Perivascular fibrosis and laminin thickness were significantly augmented in diabetic rat myocardium irrespective of insulin treatment, whereas interstitial collagen I and fibronectin were similarly found in diabetic and control myocardium. Initial stages of diabetic cardiomyopathy in hyperinsulinemic rats are characterized by cardiomyocyte hypertrophy and enhanced cardiac contractility. It is suggested that hyperinsulinemia may be involved in cardiac hypertrophy.
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PMID:Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats. 1476 80

Diabetes is a strong and independent risk factor for the development of heart failure, and once heart failure occurs, patients with diabetes have a much poorer prognosis than do those without diabetes. This difference has been explained by the existence of a distinct diabetic cardiomyopathy characterized by morphologic and structural changes to the myocardium and coronary vasculature. Despite diabetic cardiomyopathy, the pharmacologic treatment of heart failure in diabetic patients is similar to that in patients without diabetes, and in general, the clinical response of diabetic patients to drug therapies for heart failure is similar, if not superior, to that of nondiabetic patients. Subgroup analyses from large clinical studies have shown that angiotensin-converting enzyme inhibitors not only reduce mortality in diabetic patients with heart failure, but also reduce the incidence of heart failure in at-risk diabetic patients. B-Blockers remain underused in the diabetic population despite overwhelming evidence of their efficacy in treating heart failure in patients with diabetes.
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PMID:Pharmacological treatment and prevention of heart failure in the diabetic patient. 1502 9

Diabetes mellitus is one of the significant risk factors for many cardiovascular diseases. Diabetes mellitus is 3-4 times more frequent in patients with heart failure compared to patients without heart failure. Prognosis of patients with heart failure and diabetes mellitus is worse than prognosis of non-diabetic patients with the same left ventricular dysfunction. The term diabetic cardiomyopathy refers to a relation between diabetes mellitus and heart disease, but it probably isn't a separate morphology unit. In treatment of patients with diabetes mellitus general rules apply to heart failure management. The effect of ACE inhibitors was in majority of studies stronger in diabetics than in non-diabetics, the effect of beta blockers was comparable or smaller. Treatment is based on good compensation of metabolic parameters, blood pressure, titration of ACE inhibitors into recommended doses, and an optimal dose of a beta blocker. Type II diabetics with heart failure will, due to decreased resorption and metabolism, need insulin more often than diabetics without heart failure.
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PMID:[Diabetes mellitus and chronic heart failure]. 1504 Jan 57

The incidence of diabetes mellitus is becoming progressively more frequent. The majority of diabetic patients will develop cardiovascular complications, among which coronary artery disease and diabetic cardiomyopathy are the most frequent and insidious. Apart from a meticulous metabolic control of diabetes, cardiac and vascular complications should be aggressively treated using the usual drugs at present effectively employed for their treatment in the general population. Additionally, the possibility of modifying cardiac substrate metabolism of the diabetic heart appears particularly attractive. Specifically, the possibility of increasing glucose metabolism rate and, accordingly, reducing free fatty acid oxidation, appears to be a very attractive therapeutic approach. Indeed, among traditional pharmacological tools, there is growing evidence that specific metabolically active drugs, the so-called partial free fatty acid inhibitors, of which the most studied is trimetazidine, will play an increasing role in the treatment of diabetic patients with coronary artery disease and cardiomyopathy. The property of these drugs is to facilitate myocardial utilization of glucose instead of free fatty acids which, in the context of ischemic and dysfunctional myocardial cells, appears to be deleterious. Similarly to other compounds that stimulate pyruvate dehydrogenase activity thereby facilitating glucose oxidation and inhibiting free fatty acid oxidation, such as dichloroacetate, trimetazidine has been shown to improve left ventricular function in diabetic patients with heart failure. Prospective studies in large clinical trials would produce more objective and definitive insights into the specific value of these new therapeutic concepts in the treatment of diabetic patients with cardiac diseases.
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PMID:[Heart disease and diabetes: from pathophysiology to therapeutic options]. 1507 72

Diabetic cardiomyopathy is a common complication leading to heightened risk of heart failure and death. In the present report, we performed proteomic analysis on total cardiac proteins from the OVE26 mouse model of type 1 diabetes to identify protein changes that may contribute to diabetic cardiomyopathy. This analysis revealed that a surprising high proportion (12 of 20) of the altered proteins that could be identified by mass spectrometry were of mitochondrial origin. All but one of these proteins were upregulated by diabetes. Quantitative RT-PCR, performed for two of these proteins, indicated that part of the upregulation was attributed to increased messenger RNA levels. Morphological study of diabetic hearts showed significantly increased mitochondrial area and number as well as focal regions with severe damage to mitochondria. Diabetic mitochondria also showed reduced respiratory control ratio (9.63 +/- 0.20 vs. 6.13 +/- 0.41, P < 0.0001), apparently due to reduced state 3 rate, and diminished GSH level (5.5 +/- 0.9 vs. 8.2 +/- 2.5 micromol/mg protein, P < 0.05), indicating impaired mitochondrial function and increased oxidative stress. Further examination revealed increased mitochondrial DNA (1.03 +/- 0.18 vs. 0.69 +/- 0.13 relative copy number, P < 0.001) and a tendency to higher protein yield in OVE26 cardiac mitochondria, as well as increased mRNA level for mitochondrial transcription factor A and two mitochondrial encoded proteins. Taken together, these results show that mitochondria are a primary target in the diabetic heart, probably due to oxidative stress, and that this damage coincides with and may stimulate mitochondrial biogenesis.
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PMID:Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes. 1528 Jan 50

Although the heart is capable of extracting energy from different types of substrates such as fatty acids and carbohydrates, fatty acids are the preferred fuel under physiological conditions. In view of the presence of diverse defects in myocardial metabolism in the failing heart, changes in metabolism of glucose and fatty acids are considered as viable targets for therapeutic modification in the treatment of heart failure. One of these changes involves the carnitine palmitoyltransferase (CPT) enzymes, which are required for the transfer of long chain fatty acids into the mitochondrial matrix for oxidation. Since CPT inhibitors have been shown to prevent the undesirable effects induced by mechanical overload, e.g. cardiac hypertrophy and heart failure, it was considered of interest to examine whether the inhibition of CPT enzymes represents a novel approach for the treatment of heart disease. A shift from fatty acid metabolism to glucose metabolism due to CPT-I inhibition has been reported to exert beneficial effects in both cardiac hypertrophy and heart failure. Since the inhibition of fatty acid oxidation is effective in controlling abnormalities in diabetes mellitus, CPT-I inhibitors may also prove useful in the treatment of diabetic cardiomyopathy. Accordingly, it is suggested that CPT-I may be a potential target for drug development for the therapy of heart disease in general and heart failure in particular.
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PMID:Carnitine palmitoyltransferase-I, a new target for the treatment of heart failure: perspectives on a shift in myocardial metabolism as a therapeutic intervention. 1528 95


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