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)

Oxidative stress is associated with muscle fatigue and weakness in skeletal muscle of ischemic heart disease patients. Recently, it was found that endurance training elevates protective heat shock proteins (HSPs) and antioxidant enzymes in skeletal muscle in healthy subjects and antioxidant enzymes in heart failure patients. However, it is unknown whether coronary ischemia and mild infarct without heart failure contributes to impairment of stress proteins and whether exercise training reverses those effects. We tested the hypothesis that exercise training would reverse alterations in muscle TNF-alpha, oxidative stress, HSP70, SOD (Mn-SOD, Cu,Zn-SOD), glutathione peroxidase (GPX), and catalase (CAT) due to chronic coronary occlusion of the left circumflex (CCO). Yucatan swine were divided into three groups (n = 6 each): sedentary with CCO (SCO); 12 wk of treadmill exercise training following CCO (ECO); and sham surgery controls (sham). Forelimb muscle mass-to-body mass ratio decreased by 27% with SCO but recovered with ECO. Exercise training reduced muscle TNF-alpha and oxidative stress (4-hydroxynonenal adducts) caused by CCO. HSP70 levels decreased with CCO (-45%), but were higher with exercise training (+348%). Mn-SOD activity, Mn-SOD protein expression, and Cu,Zn-SOD activity levels were higher in ECO than SCO by 72, 82, and 112%, respectively. GPX activity was 177% greater in ECO than in SCO. CAT trended higher (P = 0.059) in ECO compared with SCO. These data indicate that exercise training following onset of coronary artery occlusion results in recovery of critical stress proteins and reduces oxidative stress.
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PMID:Exercise training reverses downregulation of HSP70 and antioxidant enzymes in porcine skeletal muscle after chronic coronary artery occlusion. 1687 55

Caloric restriction extends longevity and reduces the onset of chronic disease in many animal models. Recently, caloric restriction was shown in humans to be associated with lower blood pressure, decreased systemic inflammation, and improved cardiac diastolic parameters. However, the causation and mechanisms of caloric restriction were obscured by the varied diet composition of the participants. The Dahl salt-sensitive rat which develops gradual, hypertension-associated diastolic dysfunction was used in this study to assess the impact of caloric restriction upon decompensated pressure-overload hypertrophy. Male Dahl salt-sensitive rats were provided either a low-salt diet or a high-salt diet to initiate heart failure progression. A further subset of high-salt rats underwent 15% calorie restriction, with salt load held constant. Parameters measured included serial systolic blood pressure, body weight, and changes of left ventricular systolic and diastolic parameters and ventricular geometry by echocardiography. After 18 weeks, fasting glucose, blood lipids, heart weight, kidney weight, lung weight, plasma interleukin-6 and TNF-alpha, and cardiac lipid peroxidation were measured. Low-salt rats did not develop heart failure. While high-salt rats displayed features of decompensated pressure-overload hypertrophy, moderate calorie restriction remarkably reduced morbidity. Compared to the high-salt fed group, the high-salt, calorie-restricted group showed reduced blood pressure, delayed onset of cachexia, lower fasting hyperlipidemia, lower cardiac, renal and lung weight, less plasma IL-6 and TNF-alpha, less cardiac oxidative damage, and improved diastolic chamber function and cardiac index. Modest calorie restriction, independent of salt intake, reduced pathogenesis in this well described model of decompensated pressure-overload hypertrophy.
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PMID:Moderate calorie restriction improves cardiac remodeling and diastolic dysfunction in the Dahl-SS rat. 1693 90

Blocking brain mineralocorticoid receptors (MRs) reduces the high circulating levels of tumor necrosis factor (TNF)-alpha in heart failure (HF) rats. TNF-alpha and other proinflammatory cytokines activate neurons in the paraventricular nucleus (PVN) of hypothalamus, including corticotropin-releasing hormone (CRH) neurons, by inducing cyclooxygenase (COX)-2 activity and synthesis of prostaglandin E2 by perivascular cells of the cerebral vasculature. We tested the hypothesis that systemic treatment with a MR antagonist would reduce hypothalamic COX-2 expression and PVN neuronal activation in HF rats. Rats underwent coronary ligation to induce HF, confirmed by echocardiography, or sham surgery, followed by 6 weeks treatment with eplerenone (30 mg/kg per day, orally) or vehicle (drinking water). Eplerenone-treated HF rats had lower plasma TNF-alpha, interleukin (IL)-1beta and IL-6, less COX-2 staining of small blood vessels penetrating PVN, fewer PVN neurons expressing Fra-like activity (indicating chronic neuronal activation), and fewer PVN neurons staining for TNF-alpha, IL-1beta, and CRH than vehicle-treated HF rats. COX-2 and CRH protein expression in hypothalamus were 1.7- and 1.9-fold higher, respectively, in HF+vehicle versus sham+vehicle rats; these increases were attenuated (26% and 25%, respectively) in HF+eplerenone rats. Eplerenone-treated HF rats had less prostaglandin E2 in cerebrospinal fluid, lower plasma norepinephrine levels, lower left ventricular end-diastolic pressure, and lower right ventricle/body weight and lung/body weight ratios, but no improvement in left ventricular function. Treatment of HF rats with anticytokine agents, etanercept or pentoxifylline, produced very similar results. This study reveals a previously unrecognized effect of MR antagonism to minimize cytokine-induced central neural excitation in rats with HF.
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PMID:Novel effect of mineralocorticoid receptor antagonism to reduce proinflammatory cytokines and hypothalamic activation in rats with ischemia-induced heart failure. 1696 Jan

Elevated circulating levels of alpha- and beta-chemokines in heart failure have been reported. The objective of this study was to investigate the interrelation of chemotactic activity of serum and circulating chemokine levels in patients suffering from idiopathic dilated cardiomyopathy (IDCM). Chemokine serum levels (MCP-1, MIP1-alpha, RANTES, IL-8 and TNF-alpha) were determined in patients with IDCM (n = 10), patients with coronary artery disease with normal (CAD-1; n = 10) or depressed (CAD-2; n = 10) left ventricular function and healthy controls (n = 10). The chemotactic effect of sera obtained from these groups was measured using an in vitro chemotaxis assay. Sera obtained from IDCM (5475 +/- 681 cells) showed the highest chemotactic activity when compared to controls (1850 +/- 215 cells), CAD-1 (3325 +/- 275 cells) and CAD-2 (2800 +/- 275 cells, P < 0.05) associated with significantly higher circulating MCP-1 levels. Sera obtained from IDCM patients show a high chemotactic activity associated with significantly elevated circulating MCP-1.
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PMID:Chemotactic activity of serum obtained from patients with idiopathic dilated cardiomyopathy. 1696 15

Worldwide, over 400,000 patients have been treated with tumour necrosis factor (TNF)-alpha antagonists for indications that include rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis. Since their approval, concerns regarding safety have been raised. There is a risk of re-activation of granulomatous diseases, especially tuberculosis, and measures should be taken for detection and treatment of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted in re-activation of chronic hepatitis B if not given concurrently with antiviral therapy. Solid tumours do not appear to be increased with anti-TNF therapy. Variable rates of increased lymphoma risk have been described with anti-TNF therapy compared with the general population, although no increased risk was found compared with a rheumatoid arthritis population. Large phase II and III trials with TNF-alpha antagonists in advanced heart failure have shown trends towards a worse prognosis, and should therefore be avoided in this population. Both etanercept and infliximab are associated with the formation of autoantibodies, and these autoantibodies are rarely associated with any specific clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and demyelination have been described with anti-TNF therapy. This chapter will discuss the safety profile and adverse events of the three commercially available TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented in this review have been collected from published data, individual case reports or series, package inserts, the Food and Drug Administration postmarketing adverse events surveillance system, and abstracts from the American College of Rheumatology and European Congress of Rheumatology meetings for 2005.
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PMID:Problems encountered during anti-tumour necrosis factor therapy. 1697 37

Natriuretic peptides (NPs) comprise a family of vasoactive hormones that play important roles in the regulation of cardiovascular and renal homeostasis. Along this line, atrial NP (ANP) (international non-proprietary name: carperitide, HANP) is an approved drug for the treatment of acute heart failure. In recent years, evidence has been given that the NP system possesses a far broader biological spectrum than the regulation of blood pressure and volume homeostasis. In fact, a substantial amount of in vitro work indicates that ANP affects important inflammatory processes and signaling pathways. Quite surprisingly, however, no information exists on the in vivo antiinflammatory potential and signaling of ANP. We show here that pretreatment of lipopolysaccharide (Salmonella abortus equi, 2.5 mg/kg)-challenged mice with ANP (5 microg/kg iv, 15 min) rapidly inhibits nuclear factor-kappaB activation via inhibition of phosphorylation and degradation of the IkappaB-alpha protein. ANP also reduces Akt activation upon lipopolysaccharide injection. In ANP-pretreated mice, the increase of TNF-alpha serum concentration is markedly prevented; most importantly, the survival of these animals improved. These findings demonstrate both in vitro and in vivo an antiinflammatory profile of ANP that deserves to be further investigated in a therapeutic perspective.
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PMID:Atrial natriuretic peptide, a regulator of nuclear factor-kappaB activation in vivo. 1700 92

One third of Trypanosoma cruzi-infected individuals develop chronic Chagas disease cardiomyopathy (CCC) while the majority remains asymptomatic (ASY). About 30% of CCC patients develop heart failure due to end-stage inflammatory dilated cardiomyopathy. Increased production of tumor necrosis factor (TNF)-alpha has been described in all clinical forms of Chagas disease, and the highest levels are detected in CCC patients with severe ventricular dysfunction. Genetic susceptibility may play a role in the clinical outcome of Chagas disease. We investigated TNF as a candidate gene for susceptibility to development and/or progression of CCC. We analyzed the TNFa microsatellite and the -308 TNF promoter polymorphisms, in 166 CCC compared to 80 ASY geographically and age-matched patients in an association study. To analyze the association of TNF polymorphisms with progression of the cardiomyopathy, CCC patients were also grouped in three categories according to degree of left ventricular (LV) dysfunction into severe (n=57), mild to moderate (n=21) and absent (n=88). Our results show no significant differences either between CCC and ASY patients, or among CCC patients according to severity of cardiomyopathy with respect to TNFa or -308 TNF promoter polymorphisms. These results indicate that TNF polymorphisms are associated neither to CCC development nor to progression to more severe forms of cardiomyopathy in Brazilian Chagas disease patients.
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PMID:Lack of association of tumor necrosis factor-alpha polymorphisms with Chagas disease in Brazilian patients. 1714 82

Oxidative stress plays an important role in the pathophysiology of cardiovascular disease. Recent evidence suggests that cytokines induce oxidative stress and contribute to cardiac dysfunction. In this study, we investigated whether increased circulating and tissue levels of tumor necrosis factor (TNF)-alpha in congestive heart failure (CHF) modulate the expression of NAD(P)H oxidase subunits, Nox2 and its isoforms, in the paraventricular nucleus (PVN) of the hypothalamus and contribute to exaggerated sympathetic drive in CHF. Heart failure was induced in Sprague-Dawly rats by coronary artery ligation and was confirmed using echocardiography. Pentoxifylline (PTX) was used to block the production of cytokines for a period of 5 wk. CHF induced a significant increase in the production of reactive oxygen species (ROS) in the left ventricle (LV) and in the PVN. The mRNA and protein expression of TNF-alpha, Nox1, Nox2, and Nox4 was significantly increased in the LV and PVN of CHF rats. CHF also decreased ejection fraction, increased Tei index, and increased circulating catecholamines (epinephrine and norepinephrine) and renal sympathetic activity (RSNA). In contrast, treatment with PTX in CHF rats completely blocked oxidative stress and decreased the production of TNF-alpha and Nox2 isoforms both in the LV and PVN. PTX treatment also decreased catecholamines and RSNA and prevented further decrease in cardiac function. In summary, TNF-alpha blockade attenuates ROS and sympathoexcitation in CHF. This study unveils new mechanisms by which cytokines play a role in the pathogenesis of CHF, thus underscoring the importance of targeting cytokines in heart failure.
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PMID:TNF-alpha blockade decreases oxidative stress in the paraventricular nucleus and attenuates sympathoexcitation in heart failure rats. 1741 5

Immune inflammation is an important link in pathogenesis of chronic heart failure (CHF). It has been proven that hyperproduction of proinflammatory cytokines (TNFa, IL-6, IL-1, etc) with associated endothelial dysfunction and oxidative stress affect unfavorably clinico-hemodynamic parameters and prognosis of life of patients. However attempt to augment efficacy of treatment of CHF by means of inclusion of TNFa activity inhibitors in the complex of main remedies turned out unsuccessful. At present under discussion are perspectives of application in this category of patients of statins--lipid lowering drugs with pleiotropic properties most important of which is antiinflammatory action. Theoretical obstacles for the use of statins constitute available epidemiological data on reverse relationship between cholesterol level and mortality of patients with CHF in a framework of endotoxin-lipoprotein theory. At the same time preclinical and clinical experience has been accumulated evidencing for perspectiveness of such approach. Final solution of the problem of safety and feasibility of application of statins in CHF is expected after completion of prospective randomized trials GISSI-HF and CORONA.
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PMID:[Inflammation and chronic heart failure. The role of statins]. 1742 80

Tumor necrosis factor (TNF)-alpha has been thoroughly investigated and established as a pivotal component of the inflammatory cascade. This review encompasses the safety and efficacy of TNF antagonists in rheumatoid arthritis, the interplay between rheumatoid arthritis and heart failure, as well as presentation of the available preclinical and clinical data discussing the use of anti-TNF therapy in patients with chronic heart failure. There is well-documented evidence for the role of anti-TNF-alpha in rheumatoid arthritis, in contrast to the controversial role of anti-TNF-alpha in heart failure. In animal models and small-scale clinical trials, anti-TNF therapy showed some promise in treating chronic heart failure, whereas larger, multicenter, randomized, placebo-controlled clinical trials (i.e., RECOVER [Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction] and RENAISSANCE [Randomized Etanercept North American Strategy to Study Antagonism of Cytokines]) failed to show a statistically significant difference in composite clinical function score for anti-TNF therapy versus placebo. Future investigation is needed to determine if individualized dosing of anti-TNF therapy is necessary and whether or not treating patients with earlier-stage disease will show a benefit.
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PMID:Recent advances of TNF-alpha antagonists in rheumatoid arthritis and chronic heart failure. 1747


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