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)

A phase II, open, nonrandomized trial was carried out in a group of epirubicin-treated cancer patients with the aim of detecting early preclinical changes that are predictive of the risk for heart failure. Thirty-one patients (male/female ratio, 8/23; mean age +/- standard deviation, 59 +/- 14 years) with tumors at different sites and scheduled to be treated with an epirubicin-based chemotherapy regimen, were enrolled. We prospectively evaluated the acute (1 week after) and late (3, 6, 12, and 18 months of follow-up) effects of epirubicin administration. A significant impairment in systolic left ventricular (LV) function was observed at a cumulative epirubicin dose of 200 mg/m(2). This was shown by a reduction in the strain rate (SR) peak in comparison with baseline and persisted throughout the treatment and follow-up, up to 18 months; strain (Sigma) remained unchanged. The Sm wave showed a progressive reduction that became significant only at the 18-month follow-up. On TDI the E(m)/A(m) ratio declined at the 200-mg/m(2) cumulative epirubicin dose versus baseline and persisted throughout the treatment and up to the 18-month follow-up. On conventional echocardiography the E/A ratio declined significantly only at the 300-mg/m(2) cumulative epirubicin dose. Interleukin (IL)-6, soluble IL-6 receptor, and reactive oxygen species (ROS) increased significantly at the 200-mg/m(2) dose, and IL-6 was persistently high at the 300- and 400-mg/m(2) doses, returning to within baseline values during follow-up. ROS, after the peak reached at the 200-mg/m(2) dose, returned to within baseline values. A significant inverse correlation between DeltaSR and the increase in both IL-6 and ROS was observed. A multiple regression analysis showed that both the IL-6 and ROS variables were independent and strongly predictive of DeltaSR. The clinical meaningfulness of our findings warrants further investigations on a larger number of patients for a longer period of follow-up.
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PMID:Persistence, up to 18 months of follow-up, of epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. 1906 Feb 35

Recent studies have shown that patients with heart failure over-express pro-inflammatory cytokines which enhance natural killer (NK) activity and negatively influence contractility and contribute to the remodeling of myocardium. The question is that how cardiovascular drugs influence on the cytokines of Peripheral Blood Mononuclear Cells (PBMCs) in Chronic Heart Failure (CHF). To study the effect of cardiovascular drugs on PBMCs-cytokines and NK activity of CHF patients. PBMCs of CHF patients/normal controls collected by Ficoll-paque density centrifugation. NK activity against K562 target cell was measured with MTT colorimetric assay. PBMCs were cultivated in RPMI/FCS, stimulated with phytohaemaglutinin (PHA). Tumor necrosis factor (TNF)-alpha interleukin (IL)-6, IL-2 and IL-1beta of culture supernatants after 24 h incubation with/without furosemide, captopril and digoxin were measured with sandwitch ELISA. Patients had higher NK activity than controls (56.9% +/- 1.6 vs 50.9% +/- 1.2, p < 0.05). NK activity of patients who already consumed Captopril/Furosemide didn't show difference with controls. Captopril (3, 1, 0.3 microg mL(-1)) and Furosemide (5, 2.5, 1.25 microg mL(-1)) caused a dose dependent inhibition in TNF-alpha compared with control (329 +/- 23, 427 +/- 15, 519 +/- 19 and 343 +/- 19, 430 +/- 14, respectively vs. 562 +/- 24 pg mL(-1) p < 0.05). Furosemide caused a dose dependent decrease in IL-6 (421 +/- 31, 534 +/- 33 vs. 662 +/- 41 pg mL(-1) p < 0.05). Captopril and Furosemide didn't show any significant effect on IL-1beta/IL-2. Digoxin had no significant effect on PBMCs-cytokines. These data suggest that the immunomodulatory effects of Captopril and Furosemide may contribute to their beneficial and no long-term adverse effects on PBMCs.
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PMID:The effect of cardiovascular drugs on pro-inflammatory cytokine secretion and natural killer activity of peripheral blood mononuclear cells of patients with chronic heart failure in vitro. 1908 2

We sought to evaluate the relationship between plasma cytokine levels (sCD14, tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) and tissue Doppler derived indices of left ventricular systolic and diastolic function in patients with newly diagnosed heart failure. We enrolled 101 consecutive patients (mean age 65+/-13 years) with newly diagnosed heart failure who were hospitalized in our institute. Echocardiographic assessment was performed in all patients during the third day of their initial hospitalization. The pulsed tissue Doppler imaging (TDI) of the systolic and diastolic function of mitral annulus was characterized by the systolic wave Smv, and the diastolic waves: Emv and Amv. Left atrial kinetic energy (LAKE), an index of left atrial function, was calculated using the equation 1/2 x LASV x 1.06 x Amv(2); where LASV is left atrial systolic volume. Furthermore the ratio E/Emv and the flow propagation velocity were also calculated; where E is the rapid mitral filling wave, detected by pulse Doppler. Soluble plasma levels of CD14, TNF-alpha, and IL-6 were measured in all patients during their third day of hospitalization. Linear regression analysis, after adjustment for sex, age, left ventricular ejection function, body mass index, arterial hypertension, smoking, physical activity, creatinine clearance, diabetes mellitus, and blood lipid levels, revealed that IL-6 levels were inversely associated with LAKE (b= - 5422.4+/-2031.5, P=0.03), Sm (b= -0.375+/-0.1, P=0.03), and flow propagation (b= -5.404+/-0.621, P=0.001). CD14 levels were inversely associated with flow propagation (b = -17.655+/-2.6, P=0.001), and positively associated with E/Emv ratio (b=2.58+/-3.6, P=0.002) and A/Amv ratio (b=0.629+/-0.6, P=0.04). TNF-alpha was inversely associated with Smv (b-1.189+/-0.3, P=0.005). This study reveals that increased plasma levels of CD14, IL-6 and TNF-alpha are associated with impaired left atrial function and more advanced left ventricular diastolic and systolic dysfunction, in patients with newly diagnosed heart failure.
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PMID:Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study). 1916 64

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.
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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.
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PMID:Inflammatory mediators in Chinese patients with congestive heart failure. 1939 5

Myocarditis is an important cause of heart failure in adolescents and young adults and is caused, most commonly, by viral infections. Viral myocarditis is characterized by cardiac inflammation and cardiomyocyte necrosis. The molecular pathogenesis of viral myocarditis is incomplete and specific therapies are not available. Proinflammatory cytokines such as IL-1beta, TNF-alpha and IL-6 have been implicated in the pathogenesis of myocarditis caused by encephalomyocarditis virus (EMCV) infection, a model of viral myocarditis in mice. Substance P (SP), a neuropeptide and pain transmitter, stimulates the production of proinflammatory cytokines and has been demonstrated by us and others to contribute to the pathogenesis of several viral, protozoan and helminth infections in mouse and man. Receptors for SP are expressed on the surface of cardiomyocytes, neurons, endothelial cells and immunocytes, including lymphocytes and macrophages. The current studies were performed to evaluate the role of SP in the pathogenesis of EMCV-induce myocarditis. SP levels were increased 61 fold in EMCV infected wild-type mice. EMCV infection resulted in 51% mortality at 14 days and a 1.56 fold increase in heart-to-body weight ratio that was accompanied by cardiac inflammation and necrosis and along with cardiomyocyte apoptosis and hypertrophy of surviving cells. In contrast, SP precursor knockout mice were completely protected from EMCV-mortality, cardiomegaly, cardiac inflammation and necrosis as well as cardiomyocyte apoptosis and hypertrophy. These results indicate that SP is essential for the pathogenesis of EMCV myocarditis and suggest that targeting this signaling pathway may be beneficial in viral myocarditis in humans.
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PMID:Substance P is required for the pathogenesis of EMCV infection in mice. 1943 34

Cardiac fibroblasts are the most prevalent cell type in the heart and play a key role in regulating normal myocardial function and in the adverse myocardial remodeling that occurs with hypertension, myocardial infarction and heart failure. Many of the functional effects of cardiac fibroblasts are mediated through differentiation to a myofibroblast phenotype that expresses contractile proteins and exhibits increased migratory, proliferative and secretory properties. Cardiac myofibroblasts respond to proinflammatory cytokines (e.g. TNFalpha, IL-1, IL-6, TGF-beta), vasoactive peptides (e.g. angiotensin II, endothelin-1, natriuretic peptides) and hormones (e.g. noradrenaline), the levels of which are increased in the remodeling heart. Their function is also modulated by mechanical stretch and changes in oxygen availability (e.g. ischaemia-reperfusion). Myofibroblast responses to such stimuli include changes in cell proliferation, cell migration, extracellular matrix metabolism and secretion of various bioactive molecules including cytokines, vasoactive peptides and growth factors. Several classes of commonly prescribed therapeutic agents for cardiovascular disease also exert pleiotropic effects on cardiac fibroblasts that may explain some of their beneficial outcomes on the remodeling heart. These include drugs for reducing hypertension (ACE inhibitors, angiotensin receptor blockers, beta-blockers), cholesterol levels (statins, fibrates) and insulin resistance (thiazolidinediones). In this review, we provide insight into the properties of cardiac fibroblasts that underscores their importance in the remodeling heart, including their origin, electrophysiological properties, role in matrix metabolism, functional responses to environmental stimuli and ability to secrete bioactive molecules. We also review the evidence suggesting that certain cardiovascular drugs can reduce myocardial remodeling specifically via modulatory effects on cardiac fibroblasts.
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PMID:Cardiac fibroblasts: at the heart of myocardial remodeling. 1946 Apr 3

An 11-year-old female patient, whose systemic type juvenile idiopathic arthritis (JIA) had maintained in remission for the previous 4 years while taking only a small amounts of ibuprofen, showed an abrupt 2nd relapse with congestive heart failure five days after receiving a live-attenuated rubella vaccine, which was a primary immunization. Her serum levels of anti-rubella IgM and IgG antibodies increased, and her laboratory findings such as a leukocytosis, elevated serum levels of CRP, IL-6 and other inflammatory cytokine profiles were similar to the findings observed during her previous JIA active stage. After being administration of co-therapy with steroid pulse, ibuprofen, methotrexate and phosphodiesterase inhibitor gradually improved her clinical symptoms such as spiky fever, heart failure and arthralgia. Her intermittent fever and increased serum levels of CRP and IL-6, however, have been sustained for more than 2 years, and this prolonged active clinical course therefore differed from her previous JIA active stage.This abrupt relapse only five days after vaccination was suggested not to be directly related with rubella infection, but instead to be related with the molecular mimicry between rubella and JIA.
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PMID:A relapse of systemic type juvenile idiopathic arthritis after a rubella vaccination in a patient during a long-term remission period. 1957 41

Cardiac transplantation is an effective treatment for multiple types of heart failure refractive to therapy. Although immunosuppressive therapeutics have increased survival rates within the first year posttransplant, chronic rejection (CR) remains a significant barrier to long-term graft survival. Indicators of CR include patchy interstitial fibrosis, vascular occlusion and progressive loss of graft function. Multiple factors have been implicated in the onset and progression of CR, including TGFbeta, IL-6 and connective tissue growth factor (CTGF). While associated with CR, the role of CTGF in CR and the factors necessary for CTGF induction in vivo are not understood. To this end, we utilized forced expression and neutralizing antibody approaches. Transduction of allografts with CTGF significantly increased fibrotic tissue development, though not to levels observed with TGFbeta transduction. Further, intragraft CTGF expression was inhibited by IL-6 neutralization whereas TGFbeta expression remained unchanged, indicating that IL-6 effects may potentiate TGFbeta-mediated induction of CTGF. Finally, neutralizing CTGF significantly reduced graft fibrosis without reducing TGFbeta and IL-6 expression levels. These findings indicate that CTGF functions as a downstream mediator of fibrosis in CR, and that CTGF neutralization may ameliorate fibrosis and hypertrophy associated with CR.
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PMID:Connective tissue growth factor promotes fibrosis downstream of TGFbeta and IL-6 in chronic cardiac allograft rejection. 2042 44

Binding of ligands to gp130 activates at least three different downstream signaling pathways: the signal transducer and activator of transcription (STAT), the Src-homology tyrosine phosphatase 2-ras-MAPK and the PI3K/Akt pathways. Cardiac-specific disruption of gp130 was shown to result in heart failure in response to mechano-stress accompanied by an increase in apoptosis of cardiac myocytes. Inactivation of STAT3 resulting from the loss of gp130 may be a key event in the transition from cardiac hypertrophy to heart failure. Proper vascular growth would be essential for normal cardiac development and the remodeling process. In addition to various factors, such as bcl-xL, inducible nitric oxide synthase and reactive oxygen species-scavenging proteins, VEGF has also been identified as a target gene of STAT3 and together can promote cardiac myocyte survival by preventing apoptosis and restoration of energy deprivation. In this regard, the gp130-receptor system and its main downstream mediator, STAT3, play a key role in the prevention of heart failure. In this review, current knowledge of the IL-6 family of cytokines relating to human cardiac disease is summarized, in addition to the potential role of gp130-mediated signaling systems in various models of experimental heart failure.
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PMID:gp130-mediated pathway and heart failure. 1980 22


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