UMLS:C0018801 - FACTA Search

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)

Pro-inflammatory cytokine over-expression may be implicated to the pathogenesis of anemia in chronic heart failure (CHF) through the suppression of bone marrow erythropoiesis. Erythropoietin administration has anti-inflammatory and anti-apoptotic properties in experimental CHF models and improves exercise capacity in anemic CHF patients. The present study investigates the effects of recombinant human erythropoietin analogue darbepoetin-alpha on circulating pro-inflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with CHF and anemia. Forty-one CHF patients (NYHA class: II-III; left ventricular (LV) ejection fraction (EF) <40%; hemoglobin <12.5g/dl; serum creatinine <2.5mg/dl) were randomized to receive either 3-month darbepoietin-* at 1.5 microg/kg every 20 days plus iron orally (n=21) or placebo plus iron orally (n=20). LV systolic function, plasma B-type natriuretic peptide (BNP), inflammatory markers (TNF-*, IL-6, CRP), anti-inflammatory cytokine IL-10, endothelial adhesion molecules (soluble ICAM-1 and VCAM-1) and soluble apoptosis mediators (soluble Fas, soluble Fas ligand), and 6-min walking distance were assessed at baseline and 3 months post-treatment. In darbepoetin-* treated patients, plasma BNP (451 (62-2770) from 802 (476-4440) pg/ml, p=0.002), IL-6 (6.5+/-4.7 from 10.5+/-7.8 pg/ml, p=0.013) and soluble Fas ligand (53.2+/-16.6 from 59.2+/-17.9 pg/ml, p=0.023) decreased significantly, while LVEF (32+/-6 from 26+/-6%, p<0.001), hemoglobin (12.8+/-1.4 from 10.9+/-1.0 g/dl, p<0.001) and 6-min walked distance (274+/-97 from 201+/-113m, p<0.01) increased significantly. No significant changes were observed in the placebo arm, except for a worsening in 6-min walked distance (p=0.044). In conclusion, darbepoetin-alpha reduces circulating pro-inflammatory cytokine IL-6 and apoptotic mediator soluble Fas ligand in CHF patients with anemia, with a parallel improvement of cardiac performance and exercise capacity.
...
PMID:Effects of darbepoetin-alpha on plasma pro-inflammatory cytokines, anti-inflammatory cytokine interleukin-10 and soluble Fas/Fas ligand system in anemic patients with chronic heart failure. 1799 71

Left ventricular (LV) remodeling leads to congestive heart failure and is a main determinant of morbidity and mortality following myocardial infarction. Therapeutic options to prevent LV remodeling are limited, which necessitates the exploration of alternative therapeutic targets. Toll-like receptors (TLRs) serve as pattern recognition receptors within the innate immune system. Activation of TLR4 results in an inflammatory response and is involved in extracellular matrix degradation, both key processes of LV remodeling following myocardial infarction. To establish the role of TLR4 in postinfarct LV remodeling, myocardial infarction was induced in wild-type BALB/c mice and TLR4-defective C3H-Tlr4(LPS-d) mice. Without affecting infarct size, TLR4 defectiveness reduced the extent of LV remodeling (end-diastolic volume: 103.7+/-6.8 microL versus 128.5+/-5.7 microL; P<0.01) and preserved systolic function (ejection fraction: 28.2+/-3.1% versus 16.6+/-1.3%; P<0.01), as assessed by MRI. In the noninfarcted area, interstitial fibrosis, and myocardial hypertrophy were reduced in C3H-Tlr4(LPS-d) mice. In the infarcted area, however, collagen density was increased, which was accompanied by fewer macrophages, reduced inflammation regulating cytokine expression levels (interleukin [IL]-1alpha, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, tumor necrosis factor-alpha, interferon-gamma, granulocyte/macrophage colony-stimulating factor), and reduced matrix metalloproteinase-2 (4684+/-515 versus 7573+/-611; P=0.002) and matrix metalloproteinase-9 activity (76.0+/-14.3 versus 168.0+/-36.2; P=0.027). These data provide direct evidence for a causal role of TLR4 in postinfarct maladaptive LV remodeling, probably via inflammatory cytokine production and matrix degradation. TLR4 may therefore constitute a novel target in the treatment of ischemic heart failure.
...
PMID:Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. 1823 39

Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers decreased AHR in a murine model of asthma. To elucidate the mechanisms for the beneficial effects of beta-blockers, we examined the effects of chronic administration of several beta-adrenoceptor ligands in a murine model of allergic asthma. Administration of beta-blockers resulted in a reduction in total cell counts, eosinophils, and the cytokines IL-13, IL-10, IL-5, and TGF-beta1 in bronchoalveolar lavage, and attenuated epithelial mucin content and morphologic changes. The differences in mucin content also occurred if the beta-blockers were administered only during the ovalbumin challenge phase, but administration of beta-blockers for 7 days was not as effective as administration for 28 days. These results indicate that in a murine model of asthma, chronic administration of beta-blockers reduces inflammation and mucous metaplasia, cardinal features of asthma that may contribute to airflow obstruction and AHR. Similar to heart failure, our results provide a second disease model in which beta-blockers producing an acutely detrimental effect may provide a therapeutically beneficial effect with chronic administration.
...
PMID:Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model. 1828 38

LV (left ventricular) remodelling is the basic mechanism of HF (heart failure) following MI (myocardial infarction). Although there is evidence that pro-inflammatory cytokines [including TNF-alpha (tumour necrosis factor-alpha) and IL-6 (interleukin-6)] are involved in the remodelling process, only little is known about the role of anti-inflammatory cytokines, such as IL-10. As accumulating evidence has revealed that statins possess anti-inflammatory properties, the aim of the present study was to elucidate the effect of atorvastatin on the modulation of the anti-inflammatory cytokine IL-10 and its effect on LV function in rats with HF subsequent to MI. Rats with MI, induced by permanent LAD (left anterior descending) branch coronary artery ligation, were treated for 4 weeks with atorvastatin (10 mg x kg(-1) of body weight x day(-1) via oral gavage) starting on the first day after induction of MI. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10 protein, the TNF-alpha/IL-10 ratio, serum levels of MCP-1 (monocyte chemoattractant protein-1) as well as myocardial macrophage infiltration were analysed. Treatment with atorvastatin significantly improved post-MI LV function (fractional shortening, +120%; dP/dt(max), +147%; and LV end-diastolic pressure, -27%). Furthermore atorvastatin treatment markedly decreased the levels of TNF-alpha, IL-6 and MCP-1, reduced myocardial infiltration of macrophages and significantly increased myocardial and serum levels of the anti-inflammatory cytokine IL-10. Thus the balance between pro-inflammatory and anti-inflammatory cytokines was shifted in the anti-inflammatory direction, as shown by a significantly decreased TNF-alpha/IL-10 ratio. Atorvastatin ameliorated early LV remodelling and improved LV function in rats with HF subsequent to MI. Our study suggests that the modulation of the balance between pro- and anti-inflammatory cytokines towards the anti-inflammatory cytokine IL-10 is one salutary mechanism underlying how atorvastatin influences post-MI remodelling and thus improves LV function.
...
PMID:Atorvastatin enhances interleukin-10 levels and improves cardiac function in rats after acute myocardial infarction. 1897 70

Evidence has shown that pro-inflammatory cytokines, especially TNF-alpha, are involved in the inflammatory response in the remodelling process after myocardial infarction (MI). Although IL-10, an anti-inflammatory cytokine, has been shown to antagonize some of the deleterious effects of TNF-alpha, little is known about its role in post-MI left ventricular (LV) dysfunction. The aim of the present study was to investigate whether a therapy with rhIL-10 could be beneficial in an animal model of post-MI heart failure (HF). Rats with experimental MI were treated with rhIL-10 (75 microg/kg/d sc) starting directly after MI induction, and continuing for 4 weeks. Controls were untreated MI and sham-operated rats. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10, the ratio of TNF-alpha to IL-10, serum levels of MCP-1 as well as myocardial macrophage infiltration, were analyzed. Treatment with rhIL-10 significantly improved post-MI LV function (FS +127%;, dP/dt(max) +131%; LVEDP -36%). This effect was associated with a significant decrease in pro-inflammatory cytokine and chemokine levels (TNF-alpha, IL-6, MCP-1) and furthermore resulted in a reduced myocardial infiltration of macrophages.
...
PMID:Interleukin-10 improves left ventricular function in rats with heart failure subsequent to myocardial infarction. 1859 46

Radix Astragali, a Chinese medicinal herb, consists of polysaccharides and flavonoids as its main active ingredients. It has been widely used for treatment of cardiovascular diseases such as heart failure, angina pectoris, myocardial infarction and stroke in Asian countries. This study was designed to evaluate the effect of Radix Astragali on myocardial dysfunction, cardiac remodeling and morphological alteration in an experimental model of autoimmune myocarditis, a clinical condition often resulting in dilated cardiomyopathy. Experimental autoimmune myocarditis was established with a subcutaneous injection of porcine cardiac myosin into rear footpad in Lewis rats. Radix Astragali treatment was delivered via an intravenous injection (0.2 ml/100g body weight, daily) for 3 weeks. Results from transthoracic echocardiography indicated that experimental autoimmune myocarditis led to impaired myocardial contractile function which was reconciled by Radix Astragali. The experimental autoimmune myocarditis triggered profound inflammation and fibrosis in myocardium as assessed by hematoxylin and eosin (H and E) and Masson's trichrome staining. Interestingly, Radix Astragali significantly attenuated autoimmune myocarditis-induced myocardial inflammation and fibrosis. Similarly, Radix Astragali treatment alleviated autoimmune myocarditis-triggered overt lymphocyte proliferation. Furthermore, Radix Astragali significantly attenuated elevated levels of the Th1 cytokines (IFN-gamma and IL-2), and increased the Th2 cytokines (IL-4 and IL-10) in autoimmune myocarditis. Collectively, our data revealed that Radix Astragali effectively protected against cardiac functional and morphological aberrations in experimental autoimmune myocarditis.
...
PMID:Chinese medicinal herb Radix Astragali suppresses cardiac contractile dysfunction and inflammation in a rat model of autoimmune myocarditis. 1878 7

In order to assess the relationships among mood, peripheral autonomic output and circulating immunoinflammatory mediators in older individuals with decompensated heart failure (CHF), 20 consecutive patients (78+/-7 years, 35% women) admitted to the coronary care unit with a clinical diagnosis of acute/decompensated CHF of coronary origin were examined. Mood was evaluated by the 21-item Hamilton Depression Scale (HAM-D). Four patients met the criteria for major depression. Heart rate variability (HRV) analysis and the levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-6 and IL-10 were measured within 24-72 h of admission. A significant positive relationship between score in HAM-D and serum IL-6 levels was detected with a similar trend as far as IL-2 levels. Circulating IL-2 levels were strongly associated with the HRV L/H quotient, an index of increased sympathetic and/or decreased parasympathetic thoracic activity. A negative correlation between vagal activity (as assessed by HRV) and IL-4 occurred. Neither TNF-alpha nor IL-10 were detectable in this group of elderly patients. The results add to the concept that mood and autonomic unbalance are associated with increased systemic inflammation in old patients with decompensated CHF, a potential mechanism for mood-related worsened prognosis of heart failure at an advanced age.
...
PMID:Mood, Th-1/Th-2 cytokine profile, and autonomic activity in older adults with acute/decompensated heart failure: preliminary observations. 1893 52

Statins are well-known for their ability to lower serum cholesterol levels, but have properties beyond mere cholesterol reduction, including an improvement in endothelial dysfunction, release of endothelial progenitor cells, anti-inflammatory properties and a number of antitumour activities. In the present issue of Clinical Science, Stumpf et al. show that a 4-week treatment course with the lipophilic statin atorvastatin ameliorates left ventricular remodelling and function, reduces serum levels of TNF-alpha (tumour necrosis factor-alpha), IL (interleukin)-6 and MCP-1 (monocyte chemoattractant protein-1), and increases both serum and myocardial levels of IL-10. The authors hypothesize that this shift from a pro- to an anti-inflammatory response might be beneficial in the clinical setting, because patients with low levels of IL-10 may fare worse than those with higher levels. In light of the recent setbacks with rosuvastatin in large-scale clinical trials, this notion requires further investigation, but highlights the need to identify those patients with heart failure who are likely to benefit from statin therapy.
...
PMID:Statins for heart failure: still caught in no man's land? 1845 41

Tumor necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptors 1 and 2 (sTNFR1/2), and interleukin (IL)-6 are powerful predictors of mortality in chronic heart failure (CHF). Little is known, however, about the origins of proinflammatory cytokine production or the determinants of substantial interpatient variability in inflammatory activation. We prospectively examined kidney dysfunction and Type D personality (tendency to experience and inhibit emotional distress) as predictors of interpatient variability in these markers of inflammatory activation. At baseline, 125 patients with CHF were assessed for kidney dysfunction and Type D. Serum levels of proinflammatory cytokines (TNF-alpha, sTNFR1, sTNFR2, IL-6), the anti-inflammatory cytokines IL-10, and IL-1 receptor antagonist were measured at 1-year follow-up. Type D patients had higher levels of sTNFR1 (p = 0.009) and sTNFR2 (p = 0.001) and lower levels of IL-10 (p = 0.006) than patients without Type D and kidney dysfunction. Patients with kidney dysfunction also had elevated levels of sTNFR1 and sTNFR2 (p <0.0001), but their IL-10 level was not decreased. Type D personality and kidney dysfunction predicted increased sTNFR1/IL-10 and sTNFR2/IL-10 ratios (p < or =0.007); Type D also predicted an increased IL-6/IL-10 ratio (p = 0.013). Other predictors were spironolactone and older age. After adjusting for these variables, the odds for elevated ratios (highest 20%) were still increased in Type D patients (all odd ratios >3.00). In conclusion, Type D personality and kidney dysfunction independently predicted unfavorable cytokine profiles in patients with CHF and may enhance our understanding of interpatient variability in inflammatory activation in these patients.
...
PMID:Usefulness of Type D personality and kidney dysfunction as predictors of interpatient variability in inflammatory activation in chronic heart failure. 1916 97

In this study, circulating levels of proinflammatory and anti-inflammatory mediators are studied in patients with chronic heart failure (CHF) in China. Sixty-five patients with CHF and 32 control subjects are studied. The proinflammatory and anti-inflammatory cytokines interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in plasma are determined by immunoradiometric assay kits. Catecholamine (CA) in plasma is evaluated by high-performance liquid chromatography. Plasma levels of IL-6, IL-10, TNF-alpha, ANP, BNP, and CA in CHF patients are significantly higher than those in control subjects. Patients in a higher New York Heart Association (NYHA) class show higher concentrations of inflammatory mediators than those in a lower NYHA class, although the ratio of plasma IL-10 to TNF-alpha in patients with CHF is significantly lower than in the control group. It is concluded that proinflammatory and anti-inflammatory cytokine levels are increased and IL-10/TNF-alpha is decreased in Chinese patients with CHF.
...
PMID:Inflammatory mediators in Chinese patients with congestive heart failure. 1939 5

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