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)

The increasing use of implanted biomaterial devices has made it evident that no material is biologically inert. As a result of direct contact with elements of the blood circulation, such as during hemodialysis or after left ventricular assist device (LVAD) implantation, significant changes in systemic immunologic and thrombostatic functions occur. The clinical success of LVAD implantation has, nevertheless, been accompanied by complications arising from an aberrant state of monocyte and T-cell activation, leading to heightened susceptibility of circulating CD4 T cells to undergo activation-induced cell death; this results in progressive defects in cellular immunity and an increased risk of serious infection. Because of the increased state of T-cell activation and the selective loss of Th1 cytokine producing CD4 T cells, LVAD recipients also develop B-cell hyperreactivity and dysregulated immunoglobulin syntheses by unopposed production of Th2 cytokines and increased CD40 Ligand-CD40 interactions. LVADs are currently being evaluated as a permanent therapy for end-stage heart failure. Because these immune dysfunctions appear to be related to the effects of excessive biomaterial associated T-cell activation, future efforts will need to be directed at either altering the physical properties of the materials interacting with the host circulation or pharmacological intervention aimed at inhibiting T-cell activation.
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PMID:Immunobiology of left ventricular assist devices. 1093 59

A variety of clinical and experimental investigations have suggested that tumor necrosis factor alpha (TNF-alpha) may play a role in the pathophysiology of heart failure. Serum levels of TNF-alpha are elevated in patients with heart failure, and both cardiac and infiltrating cells of the myocardium can produce this proinflammatory cytokine. Both cardiac myocytes and nonmyocytes also express receptors for TNF-alpha, and experimental studies on isolated cells, muscles, and transgenic models demonstrate the ability of TNF-alpha to recapitulate functional and biochemical alterations resembling that observed in human congestive heart failure. The intracellular pathways affected by TNF-alpha include production of ceramide and an alteration in calcium metabolism. Recent studies in both animal models and clinical investigations suggest that anti-TNF-alpha therapies may limit the pathophysiologic consequences of congestive heart failure.
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PMID:The role of tumor necrosis factor alpha in the pathophysiology of congestive heart failure. 1098 Aug 92

Induction of congestive heart failure by high-frequency pacing has been reported to increase plasma levels of immunoreactive kinins in dogs. In the present study, we evaluated plasma bradykinin levels in human heart failure. Utilizing a recently developed method, we specifically measured plasma levels of bradykinin-(1-9) nonapeptide in 21 patients with chronic congestive heart failure [New York Heart Association (NYHA) stages III and IV). At the same time, we measured plasma atrial natriuretic peptide levels and plasma renin activity, and, as a marker of inflammation, plasma levels of tumour necrosis factor. In addition, 18 healthy subjects matched for gender and age served as normal controls. Plasma bradykinin concentrations were not higher in patients with chronic congestive heart failure (median 2.1 fmol/ml) than in healthy subjects (2.6 fmol/ml). In contrast, plasma atrial natriuretic peptide levels were clearly higher (patients, 63 fmol/ml; controls, 24 fmol/ml; P<0.0001), despite diuretic treatment and in the presence of high plasma renin activity (patients, 13.0 ng x h(-1) x ml(-1); controls, 0.3 ng x h(-1) x ml(-1); P<0.0001). Tumour necrosis factor was elevated in heart failure patients in NYHA class IV only (27 pg/ml, compared with 21 pg/ml in controls; P=0.013). Bradykinin, atrial natriuretic peptide and plasma renin activity levels were not correlated with the severity of the disease, as assessed by NYHA classification. These results indicate that a rather selective cytokine activation, without concomitant stimulation of the kallikrein-kinin system, occurs in human chronic congestive heart failure.
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PMID:Plasma bradykinin levels in human chronic congestive heart failure. 1105 27

Both the prevention and attenuation of chronic heart failure (CHF) are important issues for cardiologists. There are three different strategies to prevent patients from deleterious sequels. The first strategy is to remove the causes of CHF if possible; the second is to attenuate the events that may lead to CHF, such as myocardial ischaemia and reperfusion injury, cardiomyopathy and myocarditis, cardiac hypertrophy and ventricular remodelling; the third is to prevent or attenuate the progression of CHF. Adenosine has a number of actions which merit it as a possible cardioprotective and therapeutic agent for CHF. Firstly, adenosine induces collateral circulation via inducing growth factors and triggering ischaemic preconditioning, both of which induce ischaemic tolerance in advance. Adenosine is also known to reduce the release of noradrenaline, production of endothelin and attenuate the activation of renin-angiotensin system all of which are believed to cause cardiac hypertrophy and remodelling. Secondly, exogenous adenosine is known to reduce the severity of ischaemia and reperfusion injury. Thirdly, adenosine is reported to counteract neurohumoral factors, i.e., cytokine systems, known to be related to the pathophysiology of CHF. Recently, we revealed that adenosine metabolism is changed in patients with CHF and increases in adenosine levels may aid to reduce the severity of CHF. Thus, there are many potential mechanisms for cardioprotection attributable to adenosine and we postulate the use of adenosine therapy will be beneficial in patients with CHF.
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PMID:Adenosine therapy: a new approach to chronic heart failure. 1106 Aug 17

Despite the improvements in dialysis technology, the cardiovascular mortality rate is still unacceptably high among dialysis patients. It is obvious that traditional risk factors, such as hypertension, chronic heart failure (CHF), dyslipidemia and diabetes mellitus, may account for a large part of the increased cardiovascular mortality rate in these patients. However, based on recent research it could be speculated that other, non-traditional risk factors might also contribute to the high cardiovascular mortality rate in dialysis patients. Chronic inflammation, as evidenced by increased levels of pro-inflammatory cytokines and C-reactive protein (CRP), is a common feature in dialysis patients and is associated with an increased cardiovascular morbidity and mortality. Indeed, elevated levels of pro-inflammatory cytokines (such as TNF-alpha, IL-1 and IL-6) may cause malnutrition and progressive atherosclerotic cardiovascular disease by several pathogenetic mechanisms, which will be discussed in this review. Based on the strong associations observed between malnutrition, inflammation and atherosclerosis in patients with chronic renal failure (CRF) we have proposed that these features constitute a specific syndrome (MIA), which carries a high mortality rate. As elevated levels of pro-inflammatory cytokines may play a central part in the vicious circle of malnutrition, inflammation and atherosclerosis, further research is needed to investigate whether or not different anti-cytokine treatment strategies may improve survival in dialysis patients.
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PMID:Inflammatory and atherosclerotic interactions in the depleted uremic patient. 1111 78

The development of chronic heart failure (CHF) includes phenotypic changes in a host of homeostatic systems so that, as the disease advances, CHF may be seen as a multi-system disorder with its origins in the heart but embracing many extra-cardiac manifestations. Immunological abnormalities are recognised in this context, in particular, changes in the expression of mediators of the innate immune response. Higher levels of the pro-inflammatory cytokine tumor necrosis factor (TNF) are found in the circulation and in the myocardium of patients with CHF than in controls, and TNF has been implicated in a number of pathophysiological processes that are thought important to the progression of CHF. Therapies directed against this cytokine therefore represent a novel approach to heart failure management. Anti-TNF strategies in CHF may target the mechanisms of immune activation, the intracellular pathways regulating TNF production, or the fate of TNF once it has been released into the circulation. Circulating endotoxin may be an important stimulus to TNF production by circulating monocytes, tissue macrophages and cardiac myocytes in CHF and efforts to limit this phenomenon are of interest. Several established pharmacological therapies for patients with CHF, including angiotensin converting enyzme inhibitors, beta-blockers, and phosphodiesterase inhibitors may modify cellular TNF production by their action on intracellular mechanisms, whereas TNF receptor fusion proteins have been developed that target circulating TNF itself. Patients with New York Heart Association class IV symptoms, those with cardiac cachexia and those with oedematous decompensation of their disease have the highest serum TNF levels and are most likely to benefit most from such a therapeutic approach.
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PMID:Tumour necrosis factor in chronic heart failure: a peripheral view on pathogenesis, clinical manifestations and therapeutic implications. 1115 10

The production of nitric oxide is impaired in patients with clinical and instrumental signs of arteriosclerosis (chronic coronary heart disease, stable and unstable angina, myocardial infarction); the NO deficiency is assessed through the vascular response to the infusion of stimulating (acetycholine) or inhibiting (N-mono-methylarginine) substances upon NO synthesis. Also in hypertensive subjects a weak endothelium-dependent vascular relaxation was documented, but this phenomenon is not constant and is still to be confirmed. In hypercholesterolemic patients a hyporesponsive endothelium-dependent vasodilation has been well documented, lipid lowering agents (drugs, apheresis) improve endothelium function. In heart failure low NO levels are found proportionally to the severity of disease: the expression of No is depressed, but cytokine mediated i NOS expression is enhanced, causing exaggerated amounts of NO and producing myocyte damage or death. Interesting findings indicated NO inhalation as a useful tool for reducing pulmonary hypertension and congestive heart failure.
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PMID:Cardiovascular diseases and nitric oxide in humans. 1121 29

Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still unclear, it is widely accepted that a complex interplay between viral infections and immune mechanisms is the basis of disease genesis. Previously, we showed that heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie virus B3+-IDC shared a preferential usage of three variable gene segments of the T cell receptor beta chain-(TCR-Vbeta) encoding families Vbeta3, 7 and 13.1. This indicated the possible presence of a superantigen-driven immune response. Here, we further investigated the IDC immunological scenario by analysing different phenotypes of heart-infiltrating cells: TCR repertoires, cytokine expression and presence of enterovirus-specific antigens. IDC patients who underwent heart transplantation at different times after the onset of heart failure were studied. A cardiac infiltrate of CD4+ and CD8+ T cells was present together with activated macrophages. Furthermore, the same Vbeta gene families, previously found to be skewed in hearts from fulminant cases of CVB3+-IDC, together with two additional Vbeta gene families, Vbeta1 and 5B, were increased. IL-1beta, IL-2, IL-6 and IFN-gamma were expressed in the myocardium while others, like IL-4 were not. In conclusion, an orchestrated complex of immune mechanisms seems to be the basis of IDC etiopathogenesis.
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PMID:Analysis of TCR Vbeta repertoire and cytokine gene expression in patients with idiopathic dilated cardiomyopathy. 1122 91

Cardiotrophin-1 (CT-1) is a recently identified cytokine of the interleukin-6 (IL-6) family that signals through the gp130 signalling pathway. CT-1 may be of central importance to the pathogenesis of ventricular remodelling in patients with acute myocardial infarction (AMI) and therefore have clinical value in the identification of patients with impaired ventricular function. Central to the clinical use of CT-1 is in the in vitro stability of the peptide. Twelve subjects were recruited. A total of 25 mL of peripheral venous blood was collected into chilled polypropylene tubes containing EDTA and aprotinin and divided into 5 aliquots. One sample was spun in a prerefrigerated centrifuge (4 degrees C) at 3,000 rpm for 10 minutes and plasma separated and frozen at -70 degrees C immediately. Remaining samples were stored for 24 and 48 hours at room temperature or on ice. CT-1 in extracted plasma specimens was measured with a competitive chemiluminescent assay. The concentration of CT-1 in samples stored optimally was 43.1 +/- 6.05 fmol/mL. CT-1 levels for storage at room temperature compared with ice at the remaining time points were as follows: 24 hours, 41.5 +/- 5.76 v 37.5 +/- 8.66; and 48 hours, 42.6 +/- 6.28 v 41.0 +/- 5.42 fmol/mL. There were no significant changes in concentrations of CT-1 stored optimally or kept for up to 48 hours in aliquots of whole blood at room temperature or on ice. We conclude that CT-1 is stable in specimens of whole blood treated with EDTA and aprotinin and stored for up to 48 hours at room temperature or on ice, hence permitting its development in the routine clinical investigation of patients with heart failure.
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PMID:Prolonged stability of endogenous cardiotrophin-1 in whole blood. 1122 35

Tumor necrosis factor alpha (TNF alpha) is a cytokine with proinflammatory properties which produces negative inotropic effects on the heart. It is produced in a variety of conditions such as septic shock, acute myocarditis, reperfusion injury, and congestive hear failure (CHF). This production is probably due to activation of immune elements localized in the heart or periphery, or both. TNF alpha acts by binding to two specific receptors: TNF-R1 and TNF-R2. These two proteins have different effects. TNF-R1 has cytotoxic and antiviral activity, induces fibroblast proliferation, and mediates apoptosis. TNF-R2 is involved in septic shock and in lymphocyte proliferation. They both have negative inotropic effect on the heart. It has been showed that these receptors are down-regulated in congestive heart failure, while their soluble forms (sTNF-R1 and sTNF-R2) increase with the severity of symptoms. However the significance of this increase is still unclear. The role of Fas, a receptor protein that induces apoptosis, is also examined. Fas and its ligand have homologies respectively with TNF alpha and TNF-R. Also the soluble form of Fas (sFas) increases in relation to heart failure and is related to soluble forms of the similar receptor family, therefore it is possible that the same stimuli lead the three receptors to act together. SFas, as well as sTNF receptors, may play an important role in CHF.
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PMID:[TNF alpha and heart failure]. 1125 33


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