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)

In 1996 and 1997, 52 patients were admitted to the Princess Margaret Hospital, Nassau, Bahamas, with a confirmed diagnosis of acute myocardial infarction (AMI). The average time to presentation after the onset of symptoms was 18 hours, with 56% of patients presenting within 12 hours. Risk factors identified for ischaemic heart disease were hypertension (77%), obesity (62%), diabetes mellitus (35%), tobacco smoking (25%), a family history of coronary artery disease (17%) and hypercholesterolaemia (8%). Medications administered in the treatment of AMI included oral nitrates (96%), intravenous heparin (90%), beta-blockers (65%), morphine (15%), thrombolytic agents (8%) and lignocaine (4%). In hospital post myocardial infarction complications were angina (23%), arrhythmias (12%) and cardiac failure (10%). The average hospital stay was eight days, with a mortality rate of 19%. These results show that there is considerable room for improvement, particularly in the use of thrombolytic therapy, to ensure that all patients receive optimal acute and post myocardial infarction care.
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PMID:Management of acute myocardial infarction in the public sector in the Bahamas. 1094 48

Atherosclerosis, a chronic systemic disease of the vasculature with an inflammatory component, is the primary cause of cardiovascular morbidity and mortality in industrialized countries. It is associated with the impairment of endothelium-dependent relaxation in the coronary, systemic circulation due to decreased bioavailability of nitric oxide, and increased release oxygen-derived free radicals, thus promoting vasoconstriction, leukocyte adhesion, thrombosis, inflammation, and cell proliferation. Expression of endothelin (ET)-1, a 21-amino acid peptide and major isoform of the endothelin peptide family, is produced by endothelial, vascular smooth muscle cells, and macrophages and acts through Gi-protein-coupled ET(A) and ET(B) receptors. Endothelin-1 increases in hypercholesterolemia and atherosclerosis in humans and experimental animals. This paper reviews current experimental and clinical evidence for the involvement of ET-1 in atherogenesis. Furthermore, the effects of ET receptor blockade on experimental hypercholesterolemia and atherosclerosis will be discussed. As chronic endothelin blockade inhibits fatty streak formation and improves vascular function in experimental hypercholesterolemia, hypertension, and heart failure, and as it restores nitric oxide (NO)-mediated endothelial function and reduces atheroma formation in animals with atherosclerosis, endothelin receptor blockade may therefore offer a novel approach for the treatment of atherosclerosis and its vascular complications.
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PMID:Endothelial dysfunction and atherosclerosis: endothelin receptor antagonists as novel therapeutics. 1098 Nov 33

Sphingomyelin and its metabolic products are now known to have second messenger functions in a variety of cellular signaling pathways. At the epicenter of the sphingomyelin--cell signaling pathway is a family of phospholipases called sphingomyelinases. These enzymes cleave sphingomyelin to produce ceramide and phosphocholine. Ceramide in turn serves as a lipid second messenger that induces a variety of cell regulatory phenomenon such as programmed cell death (apoptosis), cell differentiation, cell proliferation, and sterol homeostasis. Neutral sphingomyelinase (N-SMase) is a Mg2+ sensitive enzyme that can be activated by a host of physiologically relevant and structurally diverse molecules like tumor necrosis factor-alpha (TNF-alpha), oxidized human low density lipoproteins (Ox-LDL), and several growth factors. Large amounts of ceramide accumulate in human fatty streaks and plaques along with Ox-LDL, growth factors, and proinflammatory cytokines in human atherosclerosis. A further role of ceramide and N-SMase in atherosclerosis was uncovered by the finding that Ox-LDL and TNF-alpha stimulated N-SMase activity. In turn, ceramide and/or a homolog serves as an important stress signaling molecule in signal transduction, which leads to apoptosis. Interestingly, an antibody against N-SMase can abrogate Ox-LDL and TNF-alpha induced apoptosis, and therefore may be useful for additional studies of apoptosis in experimental animals. Overexpression of recombinant human N-SMase in human aortic smooth muscle cells markedly stimulate apoptosis, presumably via the multioligomerization of the 'death domain'. Since plaque stability is an integral aspect of atherosclerosis management, activation of N-SMase and subsequent apoptosis may be vital events in the onset of plaque rupture, stroke and heart failure. In contrast to these observations in human hepatocytes, TNF-alpha mediated N-SMase activation did not induce apoptosis. Rather it stimulated the maturation of sterol regulatory element (SRE) binding protein (SREBP-1). Moreover, a cell permeable ceramide was found to reconstitute the phenomenon above in a sterol-independent fashion. These findings provide alternate avenues for therapy of patients with hypercholesterolemia and atherosclerosis. The findings reported here suggests that N-SMase plays important cell regulatory roles and provide an exciting opportunity to further these findings to understand the pathophysiology of human disease states.
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PMID:Neutral sphingomyelinase: past, present and future. 1100 63

The advent of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) has revolutionised the treatment of hypercholesterolaemia. Statin treatment, by lowering the atherogenic lipoprotein profile, reduces morbidity and mortality in patients with cardiovascular disease. Treatment with simvastatin causes a reduction of events of new-onset heart failure, but this may be attributable to properties other than its lipid-lowering effects. There is some evidence that lower serum cholesterol concentrations (as a surrogate for the totality of lipoproteins) relate to impaired survival in patients with chronic heart failure (CHF). Inflammation is a feature in patients with CHF and increased lipopolysaccharide may contribute substantially. We postulate that higher concentrations of total cholesterol are beneficial in these patients. This is potentially attributable to the property of lipoproteins to bind lipopolysaccharide, thereby preventing its detrimental effects. We hypothesise there is an optimum lipoprotein concentration below which lipid reduction would, on balance, be detrimental. We also propose that, in patients with CHF, a non-lipid-lowering statin (with ancillary properties such as immune modulatory and anti-inflammatory actions) could be as effective or even more beneficial than a lipid-lowering statin.
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PMID:The endotoxin-lipoprotein hypothesis. 1114 16

L-Arginine (Arg) is the substrate for the synthesis of nitric oxide (NO), the endothelium-derived relaxing factor essential for regulating vascular tone and hemodynamics. NO stimulates angiogenesis, but inhibits endothelin-1 release, leukocyte adhesion, platelet aggregation, superoxide generation, the expression of vascular cell adhesion molecules and monocyte chemotactic peptides, and smooth muscle cell proliferation. Arg exerts its vascular actions also through NO-independent effects, including membrane depolarization, syntheses of creatine, proline and polyamines, secretion of insulin, growth hormone, glucagon and prolactin, plasmin generation and fibrinogenolysis, superoxide scavenging and inhibition of leukocyte adhesion to nonendothelial matrix. Compelling evidence shows that enteral or parenteral administration of Arg reverses endothelial dysfunction associated with major cardiovascular risk factors (hypercholesterolemia, smoking, hypertension, diabetes, obesity/insulin resistance and aging) and ameliorates many common cardiovascular disorders (coronary and peripheral arterial disease, ischemia/reperfusion injury, and heart failure). Dietary Arg supplementation may represent a potentially novel nutritional strategy for preventing and treating cardiovascular disease.
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PMID:Arginine nutrition and cardiovascular function. 1105 97

The common carotid intima-media thickness (CC IMT) is a strong predictor for cardiovascular disease in patients with end-stage renal failure. However, little is known about possible associations between potential cardiovascular risk factors such as serum total homocysteine concentrations (tHcy) and the CC IMT. Thus, we investigated (a) the course of tHcy levels after renal transplantation (RTX) and (b) the relationship between CC IMT and tHcy in 53 renal allograft recipients with chronic renal failure before transplantation and 3, 6, and 12 months after transplantation. Exclusion criteria were volume overload, symptomatic coronary artery disease, symptomatic cerebrovascular disease, peripheral artery disease, heart failure, valvular heart disease, diabetes mellitus, severe hypercholesterolemia, and blood pressure above 159/89 mmHg at the time of the investigation. In all renal allograft recipients, a carotid high-resolution B-mode ultrasound measurement of the CC IMT was performed. Eighteen patients had normal ( < 20 micromol/L) pre-transplant (U0) tHcy, 25 had moderately elevated (20-40 micromol/L) pre-transplant (U0) tHcy, and 10 had severely elevated (> 40 micromol/L) pre-transplant (U0) tHcy. After 12 months of follow-up time (U12), no statistically significant differences concerning the tHcy levels could be detected between the groups (average serum tHcy 16.4 micromol/L +/- 1.1 micromol/L). The CC IMT did not differ significantly between the three tHcy groups at any time within the present follow-up. This was also true for the 'wall-to-lumen ratio'. A multiple forward stepwise regression analysis showed that the reduction of the CC IMT was positively correlated with gender (p < 0.01), glucose levels at U12 (p < 0.05; r2 = 0.96), systolic arterial blood pressure at U12 (p < 0.05; r2 = 0.97), and with the intact parathyroid hormone levels at U0 (p < 0.01; r2 = 0.98). In conclusion, (a) tHcy decreases significantly after RTX, but (b) does not influence the CC IMT thickness independently.
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PMID:Effect of homocysteine on carotid intima-media thickness after renal transplantation. 1112 8

Analogues of L-arginine that are chemically modified at the terminal guanidino nitrogen group, such as Nomega-monomethy-L-arginine (L-NMMA), have been used for nitric oxide synthase inhibition. However, L-NMMA and other methylated L-arginine analogues are also endogenously formed. Among these, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been shown to be the most abundant. Like L-NMMA, ADMA is an inhibitor of NO synthase, whereas SDMA is inactive. ADMA is synthesized by N-methyltransferases, a family of enzymes that methylate L-arginine residues within specific proteins. Free ADMA is released during proteolytic cleavage of methylated proteins; it can be detected in plasma and urine, but its intracellular concentrations appear to be much higher. ADMA is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), and inhibition of DDAH activity has been shown to lead to increased ADMA levels and endothelial dysfunction. Plasma levels of ADMA are elevated in endstage renal failure, in atherosclerosis and hypercholesterolemia, in hypertension, and in heart failure. Although the molecular cause for elevation of ADMA concentration in these diseases has not been fully elucidated, evidence is accumulating that ADMA is one cause of endothelial dysfunction in these diseases. Moreover, it may be a marker or even a risk factor for cardiovascular disease. Therefore, pharmacological modulation of ADMA concentration may be a novel therapeutic target in cardiovascular diseases.
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PMID:Asymmetric dimethylarginine, derangements of the endothelial nitric oxide synthase pathway, and cardiovascular diseases. 1112 10

Endothelial dysfunction is associated with hypertension, hypercholesterolemia, and heart failure. We tested the hypothesis that spontaneously diabetic Goto-Kakizaki (GK) rats, a model for type 2 diabetes, exhibit endothelial dysfunction. Rats also received a high-sodium diet (6% NaCl [wt/wt]) and chronic angiotensin type 1 (AT(1)) receptor blockade (10 mg/kg PO valsartan for 8 weeks). Compared with age-matched nondiabetic Wistar control rats, GK rats had higher blood glucose levels (9.3+/-0.5 versus 6.9+/-0.2 mmol/L for control rats), 2.7-fold higher serum insulin levels, and impaired glucose tolerance (all P<0.05). Telemetry-measured mean blood pressure was 15 mm Hg higher in GK rats (P<0.01) compared with control rats, whereas heart rates were not different. Heart weight- and kidney weight-to-body weight ratios were higher in GK rats (P<0.05), and 24-hour albuminuria was increased 50%. Endothelium-mediated relaxation of noradrenaline-precontracted mesenteric arterial rings by acetylcholine was impaired compared with the control condition (P<0.05), whereas the sodium nitroprusside-induced relaxation was similar. Preincubation of the arterial rings with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester and the cyclooxygenase inhibitor diclofenac inhibited relaxations to acetylcholine almost completely in GK rats but not in Wistar rats, suggesting that endothelial dysfunction can be in part attributed to reduced relaxation via arterial K(+) channels. Perivascular monocyte/macrophage infiltration and intercellular adhesion molecule-1 overexpression were observed in GK rat kidneys. A high-sodium diet increased blood pressure by 24 mm Hg and 24-hour albuminuria by 350%, induced cardiac hypertrophy, impaired endothelium-dependent relaxation further, and aggravated inflammation (all P<0.05). The serum level of 8-isoprostaglandin F(2alpha), a vasoconstrictor and antinatriuretic arachidonic acid metabolite produced by oxidative stress, was increased 400% in GK rats on a high-sodium diet. Valsartan decreased blood pressure in rats fed a low-sodium diet and prevented the inflammatory response. In rats fed a high-sodium diet, valsartan did not decrease blood pressure or improve endothelial dysfunction but protected against albuminuria, inflammation, and oxidative stress. As measured by quantitative autoradiography, AT(1) receptor expression in the medulla was decreased in GK compared with Wistar rats, whereas cortical AT(1) receptor expression, medullary and cortical angiotensin type 2 (AT(2)) receptor expressions, and adrenal ACE and neutral endopeptidase expressions were unchanged. A high-sodium diet did not influence renal AT(1), AT(2), ACE, or neutral endopeptidase expressions. In valsartan-treated GK rats, the cortical and medullary AT(1) receptor expressions were decreased in the presence and absence of a high-sodium diet. A high-sodium diet increased plasma brain natriuretic peptide concentrations in presence and absence of valsartan treatment. We conclude that hypertension in GK rats is salt sensitive and associated with endothelial dysfunction and perivascular inflammation. AT(1) receptor blockade ameliorates inflammation during a low-sodium diet and partially protects against salt-induced vascular damage by blood pressure-independent mechanisms.
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PMID:Endothelial dysfunction and salt-sensitive hypertension in spontaneously diabetic Goto-Kakizaki rats. 1123 Mar 14

Long-lasting problem on the differentiation of adenohypophyseal cell, which prepares them for their specific tasks (somatotropic, lactotropic ect.), becomes elucidated after recognition of the differentiational effect of transcription factor Pit-1. Expression of that factor in somatotrops results in STH secretion, contrary to lactotrops producing prolactin. Subclinical hypothyreosis (increased TSH with normal T3 and T4) endangers vessel not because of hypercholesterolemia, but because of changes in the dynamics of the blood flow. The idea of cardiotropic effect of thyroidal hormones is supported by the finding that administration of trijodthyronine to children after the surgical correction of heart malformations (cardiopulmonary bypass) improves myocardial function--it elevates cardiac output and decreases requirements on the intensive care. Receptors for hormones in tissues are flexible, they can be "heterooligomers" for dopamine and somatostatin. Mutations of mineralocorticoid receptor may cause hypertension in pregnancy and progesterone receptors have several isoforms. Receptors can be also activated by short exposition to a hormone. Glucocorticoids have probably also membrane receptors. Diabetes mellitus "type I" needn't to be immunogenic and DM type II not only results from down-regulation of receptors and subsequent insulin resistance, but it can be also caused by defects in insulin secretion. Insulin has receptors in the brain and participates in the appetite regulation. The attempt to use "desensibilisation" by peroraly administered insulin in patients with immunogenic DM had no effect. Stress affects memory mechanisms, heavy emotional stress during gravidity can bring congenital malformations. The decrease of mental functions in aged women depends on the level of free estradiol (the fraction, which is not bound to plasma proteins). Activation of dopaminergic neurons can be achieved by neurotropic growth factors. Nesiritide is a recombinant brain natriuretic hormone successfully tested in heart failure. The role of leptin in the appetite regulation in man is still not clear, other signalling molecules may have also an effect, e.g., ghrelin, which primarily stimulates STH secretion and brings about weight gain. Sildenafil influences nitrergic neurons elsewhere than in penis, for example it has positive effects in patients with oesophageal achalasia.
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PMID:[Endocrinology 1999-2000]. 1128 21

A group of elderly patients who did not clinically manifest coronary artery disease until after the age of 65 years were studied. Clinical and angiographic findings of these older patients were compared to findings of patients who had clinical manifestation of coronary artery disease before age 65. In both groups the most common initial manifestation was acute ischemic chest pain (62% vs 75%, NS). However, only 14 (34%) of the 41 elderly patients with chest pain sustained an acute myocardial infarction, compared to 62 (60%) of the 103 younger patients (P is less than 0.05). In 8% of the elderly patients the initial manifestation was acute heart failure not associated with an acute myocardial infarction; none of the younger patients had heart failure without an associated acute infarction (P is less than 0.002). Two percent of the patients over 65 years of age and 4% of the patients under 65 years sustained out-of-hospital cardiac arrest as the initial manifestation of coronary artery disease (NS). Risk factors were more common in the younger patients, with elevated cholesterol levels noted in 24% of the younger patients as compared to only 12% of the elderly patients (P is less than 0.05). Angiographically, elderly patients more commonly demonstrated multivessel coronary artery disease (68% vs 57%, P is less than 0.02) and left main vessel disease (11% vs 2%, P is less than 0.01). Even though multivessel coronary artery disease was common, the majority of elderly patients had normal left ventricular function, as did the younger patients; only 9% of patients in each age group had left ventricular ejection fractions of less than 35%. Treatment varied between the age groups, with coronary artery bypass surgery performed in 38% of the elderly patients as compared to 25% of the younger patients (P is less than 0.05). Only 3% of the patients in each group died during the acute hospitalization, and approximately 95% of the discharged patients in each group were still alive at 24 months mean follow up. We conclude that even though multivessel disease is usually present, coronary artery disease may be clinically silent until the patient is quite old. Left ventricular function is usually well preserved in these elderly patients, and with therapy their prognosis is excellent.
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PMID:Elderly Patients with Late Onset of Coronary Artery Disease: Clinical and Angiographic Findings. 1141 76


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