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

The glycoprotein 130 (gp 130) signalling pathway is important in the development of heart failure. Cardiotrophin-1 (CT-1), a cytokine acting via the gp 130 pathway, is involved in the process of ventricular remodelling following acute myocardial infarction (AMI) in animals. The aims of the present study were to examine the profile of plasma CT-1 following AMI in humans, and its relationship with echocardiographic parameters of left ventricular (LV) systolic function. Serial measurements of plasma CT-1 levels were made in 60 patients at 14-48 h, 49-72 h, 73-120 h and 121-192 h following AMI and at a later clinic visit. LV function was assessed using a LV wall motion index (WMI) score on admission (WMI-1) and at the clinic visit (WMI-2). Compared with values in control subjects (29.5+/-3.6 fmol/ml), the plasma CT-1 concentration was elevated in AMI patients at 14-48 h (108.1+/-15.1 fmol/ml), 49-72 h (105.2+/-19.7 fmol/ml), 73-120 h (91.2+/-14.9 fmol/ml) and 121-192 h (118.8+/-22.6 fmol/ml), and at the clinic visit (174.9+/-30.9 fmol/ml) (P<0.0001). Levels were higher following anterior compared with inferior AMI. For patients with anterior AMI, CT-1 levels were higher at the clinic visit than at earlier times. WMI-1 correlated with CT-1 at all times prior to hospital discharge (P<0.05). On best subsets analysis, the strongest correlate with WMI-1 was CT-1 level at 49-72 h (R(2)=20%, P<0.05). In conclusion, plasma levels of CT-1 are elevated soon after AMI in humans and rise further in the subsequent weeks in patients after anterior infarction. CT-1 measured soon after AMI is indicative of LV dysfunction, and this cytokine may have a role in the development of ventricular remodelling and heart failure after AMI.
 ...
PMID:Plasma cardiotrophin-1 following acute myocardial infarction: relationship with left ventricular systolic dysfunction. 1174 55

Heart failure still carries a high morbidity and mortality, necessitating new approaches for its management. Greater understanding of the pathophysiology of heart failure has opened the way for novel therapeutic approaches, including analogs of natriuretic peptides and drugs that modulate endothelin, cytokine release and endothelial vasoconstriction. Other drugs are undergoing laboratory and clinical trials that will eventually supersede or complement less optimal heart failure treatments. Clinical trials will ascertain if these new strategies in the treatment of heart failure will ultimately be successful in the management of these patients.
 ...
PMID:New pharmacological strategies for the treatment of heart failure. 1175 92

Interleukin-1 (IL-1) is a key mediator in the cytokine network, controlling important functions in the immune system, during development, infection, inflammation, cell-differentiation, tissue remodelling, and even cell death. The agonistic isoforms of IL-1 (i.e., IL-1alpha and IL-1beta), the IL-1 receptor antagonists, the receptors and receptor-associated proteins, as well as the recently identified IL-18 and its receptor belong to the IL-1 family of proteins. Activation of the IL-1beta and IL-18 precursors is performed enzymatically by caspase-1, previously termed IL-1beta-converting enzyme (ICE). This molecule is the founding member of the caspase family of enzymes, which are involved in maturation of cytokines and in initiation and execution of apoptotic processes. It has been suggested that cytokines and apoptosis are involved in pathogenesis of cardiovascular diseases such as atherosclerosis, chronic heart failure, myocarditis, cardiomyopathy, or stroke. Since IL-1, like TNF, is a central mediator in the cytokine network, it may act as a potent activator of cardiovascular cells. We know that cells of the vessel wall and the heart can produce IL-1 and respond to this mediator by production of other cytokines or regulation of other cardiovascular cell functions. Thus, this report summarizes general information about the molecules of the IL-1 family of proteins, including the caspases, as well as data regarding these proteins in relation to the vessel wall and the heart and their role in cardiovascular disease in adults and children. The summarized information indicates a role of these molecules in regulation of local inflammatory responses during cardiovascular disease.
 ...
PMID:Interleukin-1 and related proteins in cardiovascular disease in adults and children. 1177 30

An explanation for the higher incidence of cardiovascular disease and heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with doxazosin and the Vasodilator Heart Failure Trial (V-HeFT) with prazosin might be decreased expression of heat shock proteins. Heat shock proteins help to protect cells from ischemic injury by decreasing oxidation, suppressing cytokine action, refolding damaged proteins, and decreasing apoptosis. I hypothesize that alpha-adrenergic blockade decreases heat shock protein levels, thus making the heart and vascular system vulnerable to injury from pathologic processes such as ischemia, hypertension, oxidation or inflammation. Similarly, poor cardiovascular outcomes with calcium-channel blockers might be due to decreased expression of heat shock proteins.
 ...
PMID:Hypothesis to explain poor outcomes in the ALLHAT and V-HeFT trials: decreased expression of heat shock proteins. 1180 6

Inflammatory cytokines may negatively influence contractility and contribute to the remodelling process in the failing myocardium. Traditional cardiovascular drugs appear to have little influence on the overall cytokine network in chronic heart failure (CHF). Increased interest in anticytokine therapy has therefore evolved. Several small studies have used tumour necrosis factor (TNF)-alpha as a target, resulting in improved functional capacity and myocardial performance. Intravenous immunoglobulin (IVIG) represents another therapeutic approach in which the impact on myocardial performance appears to be correlated with anti-inflammatory effects. These studies demonstrate potential for immunomodulation as a therapy in addition to conventional cardiovascular treatment in CHF, but the most effective drugs in this regard have yet to be identified.
 ...
PMID:Cytokines as new treatment targets in chronic heart failure. 1180 13

Large increases in mortality related to premature atherosclerosis with coronary artery disease and stroke have been reported in patients with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APLS), or rheumatoid arthritis (RA). Studies found relative risks of 5 for myocardial infarction, 6 to 10 for stroke in SLE patients, and 3.6 for cardiovascular deaths in RA patients. The main risk factors for atherosclerosis included not only the classic factors identified in epidemiological studies such as the Framingham study (advanced age, high cholesterol levels, hypertension, diabetes mellitus, and obesity), but also prolonged glucocorticoid therapy, long duration of SLE, postmenopausal status, and heart failure. SLE per se is an independent risk factor. The current pathogenic hypothesis for atherosclerosis involves an inflammatory response (erythrocyte sedimentation rate, C-reactive protein, and fibrin), autoantibodies, immune complexes (containing antibodies to phospholipids, to oxidized LDLs, and to endothelial cells), cytokine-producing activated T cells, and bacterial or viral infections responsible for an immune response against heat shock proteins (endogenous HSP60 and its equivalent, bacterial HSP65). Early risk factor intervention and effective control of inflammation should be incorporated into the management of connective tissue disease with the goal of protecting patients against atherosclerosis.
 ...
PMID:Atherosclerosis and connective tissue diseases. 1295 20

Chronic obstructive pulmonary disease, COPD is a highly prevalent disorder of increasing medical and socio-economical importance. It is characterized by irreversible airflow obstruction. Besides airflow obstruction also other features are present. One of these is respiratory muscle weakness. Inspiratory muscle weakness is caused by hyperinflation and by generalized muscle weakness causing both respiratory and peripheral muscle dysfunction. The expiratory muscles partake in this generalized muscle weakness. Hyperinflation shortens the inspiratory muscles although in chronic hyperinflation sarcomere adaptation occurs. Generalized muscle weakness is caused by deconditioning, malnutrition, electrolyte disturbances, cardiac failure, systemic inflammation and treatment with corticosteroids causing steroid-induced myopathy. The latter disease was studied intensively both in patients and in animal models of disease. The major findings were that microscopically a myopathic pattern was present associated with generalized fiber atrophy. This is in contrast to classical belief that the atrophy would be confined to type IIx fibers. We noted severe down-regulation of the IGF-I mRNA expression, without important changes in the expression of the binding proteins. This may be responsible for the observed muscle atrophy and the myopathy. The latter is likely to be caused by a simultaneous upregulation of the ubiquitin protease pathway attacking structural proteins. Presently, we study the relationship between local and systemic cytokine expression and respiratory and peripheral muscle dysfunction in COPD patients. Respiratory and peripheral muscle dysfunction have significant consequences for COPD patients. Both respiratory and peripheral muscle dysfunction are associated with reduced exercise tolerance and reduced quality of life. Both are independent determinants of survival, in addition to the degree of airflow obstruction as measured by FEV1. Finally, also the utilization of health care resources appeared to be related to respiratory and peripheral muscle weakness. Treatment of respiratory and peripheral muscle weakness in COPD patients is possible. Respiratory and peripheral muscle training have been shown to produce beneficial effects. Nutritional intervention and anabolic steroids are only useful in combination with muscle training. Systemic administration of growth hormone and IGF-I only produces small effects. In animal models, local administration of IGF-I and transfer of the IGF-I gene transfer appear more promising for the future. Lung volume reduction surgery, LVRS, improves the force-generating capacity of the inspiratory muscles, presumably because of the geometrical alterations it causes in these muscles. It does not appear to improve intrinsic inspiratory muscle function.
 ...
PMID:Respiratory muscles in COPD: regulation of trophical status. 1181 11

Coronary artery disease (CAD) is very prevalent in Western societies and is a leading cause of mortality and morbidity. Despite decreases in mortality rates from CAD over the past 30 years, ischemic heart failure remains an important problem because people with CAD are now living longer. Hibernating myocardium may be defined as reversible left ventricular dysfunction due to chronic CAD that shows improvement in function after revascularization. Many patients with ischemic cardiomyopathy have areas of hibernating myocardium, and thus can potentially show improvement in left ventricular regional and global function if they are revascularized. Whether hibernating myocardium represents an adaptive response to hypoperfusion in the face of chronic ischemia or whether it is a degenerative process is not entirely clear. Clearly, ultrastructural changes of de-differentiation are seen, and include loss of sarcomeres and the appearance of small mitochondria and glycogen accumulation. Although the mechanisms underlying the changes in morphology and depressed contractility, and the factors governing recovery of function are not clear, changes in adrenergic receptor density, cytokine upregulation, and the degree of fibrosis may all play a role. Identification of viability is commonly performed with dobutamine echocardiography or nuclear imaging. Because patients with extensive CAD and poor left ventricular systolic function are high-risk candidates for coronary bypass surgery, the preoperative identification of viability provides important prognostic information. Patients with viable myocardium who are treated with revascularization rather than medical therapy have better outcomes in terms of survival, left ventricular function, symptoms, and exercise capacity.
 ...
PMID:Myocardial hibernation in coronary artery disease. 1182 79

The authors describe a case of high-output cardiac failure in a patient with rapidly progressing prostate cancer for which no previously described cause could be found. His new onset and increasingly worsening heart failure corresponded to the rapid spread of his prostate cancer. The authors hypothesize that a cytokine released from the neoplastic cells or the bone was responsible for the high-output cardiac failure observed in this patient. (c)2001 CHF, Inc.
 ...
PMID:High-output cardiac failure in a patient with prostate cancer. 1182 71

Heart failure is generally believed to begin with myocyte damage caused by a variety of insults, including ischemia, toxin or myocardial infection. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been hypothesized to play a pathogenetic role in the transition from compensated to decompensated heart failure. Interleukin-18 (IL-18), a recently cloned cytokine synthesized by Kupffer cells, activates macrophages. We examined the therapeutic effect of IL-18 on the modulation of TNF-alpha gene expression in failing heart in a murine model of heart failure caused by viral myocarditis. The heart weight (HW)/ body weight (BW) ratio in IL-18 treated mice 7 days after viral inoculation was significantly lower (P<0.01) than in the untreated controls. Myocardial necrosis and inflammatory cell infiltration were significantly lower in IL-18 treated mice than untreated mice 5 and 7 days after inoculation. The expression of TNF-alpha mRNA in the myocardium was significantly lower on days 5 and 7 in IL-18 treated mice than in infected untreated mice. We conclude that concurrent systemic administration of IL-18 is beneficial in mice with myocarditis, and may be mediated through reduced expression of TNF-alpha in the heart.
 ...
PMID:Interleukin-18 reduces expression of cardiac tumor necrosis factor-alpha and atrial natriuretic peptide in a murine model of viral myocarditis. 1188 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>