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)

Inflammatory cytokines are important for both cardiovascular scientists and practicing clinicians. Interleukin-6 (IL-6) has been emphasized by reports of elevated circulating as well as intracardiac IL-6 levels in patients with congestive heart failure (CHF). IL-6 may contribute to the progression of myocardial damage and dysfunction in chronic heart failure syndrome resulting from different causes. As the cause of CHF in cardiomyopathy, myocarditis, allograft rejection, and left ventricular assist device (LVADs) conditions, circulating IL-6 levels are associated with the severity of left ventricular dysfunction, and are also strong predictors of subsequent clinical outcomes. Continuous and excessive production of IL-6 promotes myocardial injury by breaking down both cytokine networks and viral clearance under viral myocarditis. Although IL-6 is likely important in the process of viral antigen presentation, early activation of immune responses and attenuation of viral replication also appear to be significant in an animal model of viral myocarditis. IL-6 can cause cardiac hypertrophy through the IL-6 signal transducing receptor component, glycoprotein 130. There are several interesting cases of cardiac myxoma complicated with mediastinal lymphadenopathy or left ventricular hypertrophy. Increased expression of IL-6 is observed in the myocardium of all donor hearts showing marked dysfunction. Myocardial IL-6 concentrations are also significantly higher in LVAD candidates compared with advanced heart failure patients. Although the IL-6 family plays a central role in the pathophysiology of cardiovascular diseases, it remains to be determined whether the IL-6 family is beneficial or detrimental. Future study will be needed to resolve this question.
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PMID:Interleukin-6 and cardiovascular diseases. 1509 Jun 95

Heart failure due to a variety of causes is accompanied by an upregulation of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). Adriamycin-induced cardiomyopathy (AIC) and heart failure is an important clinical problem. The current study investigated the expression of these cytokines in AIC and heart failure in rats. Both early and late stages of AIC was produced in rats. Myocardial gene expressions for TNF-alpha, IL-1beta and IL-6 were examined with DNA microarrays and RT-PCR. Protein levels of these cytokines in both the plasma and the myocardium were also examined by ELISA. In the early stage, myocardial mRNA expression of IL-1beta showed significant increase at 4 and 24 h, peaking at 4 h, while TNF-alpha did not change and IL-6 was undetectable. The protein levels of these three genes did not show any upregulation in the plasma or the heart. In the late stage, heart failure was confirmed by clinical signs as well as homodynamic changes. In this stage, plasma protein levels for TNF-alpha, IL-1beta and IL-6 were not changed. However, myocardial TNF-alpha mRNA expression and protein levels were significantly decreased, while both IL-1beta mRNA and protein levels were not different compared to the control group. IL-6 mRNA expression was undetectable in both normal and adriamycin-treated hearts while its protein level was not changed by adriamycin. Positive control using lipopolysaccharides (LPS) treatment (0.5 mg/kg body weight) for 2 h resulted in a significant increase in these three cytokines in the heart and plasma. These data suggest that an upregulation of cytokines may not be involved in AIC. Heart failure may in fact be accentuated by a downregulation of myocardial TNF-alpha.
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PMID:Cytokines are not upregulated in adriamycin-induced cardiomyopathy and heart failure. 1513 63

This randomized, placebo-controlled trial showed that levosimendan administration causes a significant reduction of circulating proinflammatory cytokine interleukin-6 and soluble apoptosis mediators, such as soluble Fas and Fas ligand in patients with decompensated heart failure. These immunomodulatory effects may lead to improvement of symptoms and echocardiographic markers of cardiac contractile performance in these patients.
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PMID:Effects of levosimendan on circulating pro-inflammatory cytokines and soluble apoptosis mediators in patients with decompensated advanced heart failure. 1547 43

It is known from the literature that the circulating levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are elevated in heart failure and idiopathic dilated cardiomyopathy (IDC). Few convincing data are available on the production of cytokines in hypertrophic cardiomyopathy (HC). The levels of circulating IL-6, the soluble form of the IL-6 receptor (sIL-6R), and TNF-alpha in 19 patients with HC, 31 patients with IDC, and 20 healthy subjects (control group) were examined and compared with their clinical parameters. The levels of TNF-alpha and circulating IL-6 proved to be elevated in the sera of patients with IDC. In contrast, the level of TNF-alpha was not elevated in HC, although the levels of IL-6 and sIL-6R were significantly higher than those in the sera of patients with IDC. Although elevated levels of IL-6 may correlate with the extent of left ventricular dysfunction in IDC, the markedly elevated IL-6 levels did not correlate with left ventricular function in HC. The markedly elevated TNF-alpha levels in IDC were associated with the elevated IL-6 levels, probably because of an inflammatory process and/or heart failure. In contrast, in HC, in which the New York Heart Association functional class was actually good, the even higher IL-6 and sIL-6R levels were not associated with a TNF-alpha elevation. In HC, the IL-6 and sIL-6R elevations were due to another mechanism, probably by way of the cardiotrophin-associated gp130 receptor. The sources of IL-6 production in HC are not clear yet.
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PMID:Comparison of circulating levels of interleukin-6 and tumor necrosis factor-alpha in hypertrophic cardiomyopathy and in idiopathic dilated cardiomyopathy. 1524 16

The derangement of neuro-endocrine control of circulation influences both disease evolution and response to treatment in patients with heart failure, but little data are available about the complex relationships between the degree of neuro-hormonal activation and clinical severity. We studied the relationships between cardiac natriuretic hormones (CNHs) and several neuro-hormones and immunological markers in a prospective cohort of 105 consecutive patients with cardiomyopathy (77 men and 28 women, mean age 66.7+/-12.4 years, range 33-89 years). We assayed the circulating levels of CNHs (atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)), plasma renin activity (PRA), aldosterone, cortisol, adrenaline, noradrenaline, thyroid hormones and thyroid stimulating hormone (TSH), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The concentrations of all CNHs and neurohormones were higher in patients with heart failure compared to normal subjects, except for free triiodothyronine (FT3), which was below normal values. ANP was positively related to NYHA class, IL-6, adrenaline, noradrenaline and cortisol, while negatively with ejection fraction and FT3. BNP was positively related to age, NYHA class, IL-6, TNF-alpha, adrenaline, noradrenaline and cortisol, while negatively with ejection fraction and FT3. A stepwise multiple linear regression indicated that plasma ANP depended only on ejection fraction, adrenaline and noradrenaline values, while for plasma BNP variation NYHA class contributed too. Our data confirm a progressive activation of hormonal and immunological systems in patients with heart failure. Furthermore, CNH circulating levels in heart failure are affected not only by cardiac function and disease severity, but also by activation of neuro-hormonal and stress-related cytokine systems, as well as by the thyroid hormones, even on usual medical treatment.
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PMID:Cardiac natriuretic hormones, neuro-hormones, thyroid hormones and cytokines in normal subjects and patients with heart failure. 1525 79

Heart failure (HF) is a complex clinical syndrome due to ischaemic heart disease, idiopathic cardiomyopathy, hypertension, valve heart disease and others. It is not clear if the etiology of HF influences decreased in this syndrome exercise tolerance. Controversial is also dependence of cytokine levels on etiology of HF. The aim of the study was to compare exercise capacity and cytokines levels in pts with ischaemic and dilated cardiomyopathy. We analyzed circulating levels of TNF-alpha and its soluble receptors sTNF-RI and sTNF-RII, and interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in 41 pts with CHF, functional class NYHA I-IV, mean EF--25.2 +/- 7.1%. For determination of cytokines level (using R & D System tests) venous blood was withdrawn after 30 minutes of supine rest. All underwent echocardiography and cardiopulmonary exercise stress testing. Dilated cardiomyopathy (DCM) was diagnosed in 21 pts, ischaemic (ICM) in 20 pts. Pts with DCM were younger then with ICM (48 +/- 6.6 vs 56 +/- 6.6 yrs; p = 0.001). There were no significant differences between groups concerning BMI and EF. There were no significant differences in the level of TNF-alpha and sTNF-RI between groups. There was a trend of increased sTNF-RII in pts with ICM (3179.7 +/- 832.7 vs 2699 +/- 680.1 pg/ml; p = 0,07), IL-1beta (2.55 +/- 2.41 vs 1.49 +/- 1.68 pg/ml; p = 0.087) and IL-6 (6.25 +/- 2.21 vs 4.98 +/- 3.64 pg/ml; p = 0.065), and significant increased ESR (11.2 +/- 9.5 vs 5.5 +/- 4.7 mm/h; p = 0.04). Peak VO2 was reduced in pts with ICM group as compared to those with DCM (14.1 +/- 3.7 vs 18.1 +/- 4.8 ml/kg/min; p = 0.0069). In chronic heart failure circulating levels of cytokines tended to be higher in pts with ischaemic origin of the syndrome. The exercise capacity is lower in ischaemic cardiomyopathy.
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PMID:[Cardiopulmonary exercise testing and cytokines in chronic heart failure. Comparison of patients with ischaemic and with dilated cardiomyopathy]. 1550 92

This clinical study compared the expression of circulating proinflammatory (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6) and anti-inflammatory (interleukin-10) cytokines and soluble apoptosis mediators (Fas/Fas ligand) between patients with stable chronic heart failure and depressive symptoms (as estimated by the Zung Self-Rating Depression Scale) (n = 15) and those without these symptoms (n = 20). Patients with depressive symptoms exhibited significantly higher levels of TNF-alpha and soluble Fas ligand, as well as significantly lower levels of interleukin-10, than patients without emotional distress. A disregulated cytokine network and activated apoptosis signaling molecules may be actively implicated in the pathophysiology of chronic emotional distress and depressive symptoms in patients with heart failure.
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PMID:Comparison of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure with versus without symptoms of depression. 1554 Dec 60

Urotensin-II (U-II), the most potent mammalian vasoconstrictor identified, and its receptor, UT, exhibits increased expression in cardiac tissue and plasma in congestive heart failure (CHF) patients. Cardiomyocyte hypertrophy is primarily responsible for increased myocardial mass associated with cardiac injury. Neurohumoral factors such as angiotensin-II, endothelin-1, catecholamines, and inflammatory cytokines are thought to mediate this response. U-II shares similar biological activities with other hypertrophic G(q)-coupled receptor ligands such as angiotensin-II and endothelin-1, but a role for U-II in cardiomyocyte hypertrophy has not been characterized. The hypothesis of the current study was that U-II, acting through its G(q)-coupled receptor UT plays a hypertrophic role in cardiac hypertrophic remodeling. We report that adenoviral upregulation of the UT receptor "unmasked" U-II-induced hypertrophy in H9c2 cardiomyocytes, with a threshold response of 202+/-8 binding sites/cell. U-II was equally as efficacious as phenylephrine in inducing hypertrophy, measured by a reporter assay (EC(50) 0.7+/-0.2 nM) and [(3)H]-leucine incorporation (EC(50) 150+/-40 nM). A competitive peptidic UT receptor antagonist, BIM-23127, inhibited U-II-induced hypertrophy ( K(B) 34+/-6 nM). U-II did not affect cell proliferation or apoptosis, indicating that U-II is more hypertrophic than apoptotic or hyperplastic in cardiomyocytes. U-II (10 nM) stimulated interleukin-6 release in UT-expressing cardiomyocytes (4.6-fold at 6 h). Finally, in a rat heart failure model, cardiac ventricular mRNA expression of U-II, UT receptor, interleukin-6, and interleukin-1-beta is increased time-dependently following myocardial injury. These results indicate that U-II might play a role in cardiac remodeling associated with CHF by stimulation of cardiomyocyte hypertrophy via UT, and through upregulation of inflammatory cytokines. As such, UT antagonism may represent a novel therapeutic target for the clinical management of heart failure.
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PMID:Urotensin-II-mediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators. 1554 73

Acute renal failure (ARF) affects about 10% of severely ill neonates. Recent studies have shown that genetic polymorphisms of proteins that play a role in neonatal physiology may contribute to individual susceptibility to both ARF and its risk factors. Our review summarizes the data collected to date. Studies have shown that the risk of preterm neonates for ARF is directly associated with a combination of high tumor necrosis factor-alpha producer and low interleukin-6 producer genotypes, as well as with low heat shock protein 72 producer genotype. Premature birth is itself the most important risk factor for a number of complications, including ARF, and recent studies have also shown an association between several maternal and fetal cytokine genetic polymorphisms and increased inflammatory response in preterm neonates. These polymorphisms could also be associated with increased risk for disorders such as sepsis and necrotizing enterocolitis, which lead to renal hypoperfusion and ARF. Genetic polymorphisms of the renin-angiotensin-aldosterone system have not been shown to directly influence risk for ARF. They may, however, be associated with patent ductus arteriosus, poor postnatal adaptation, and heart failure, which are all prevalent risk factors for ARF.
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PMID:Genetic polymorphisms and risk for acute renal failure in preterm neonates. 1562 70

We examined the plasma levels of soluble Fas (sFas) or Fas ligand (sFas-L), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in patients with idiopathic nonobstructive (HNCM) and dilated-phase (DHCM) hypertrophic cardiomyopathy. Patients with idiopathic hypertrophic cardiomyopathy (HCM) may deteriorate to DHCM and the pathogenesis is unknown. The levels of these plasma cytokines were measured by ELISA and echocardiography was performed in 38 HNCM and 11 DHCM patients, and 10 normal subjects. The follow-up period was three years. In HNCM, TNF-alpha (43.3 +/- 45.2 versus 16.9 +/- 4.3 pg/mL) and IL-6 (65.1 +/- 86.4 versus 4.0 +/- 2.1 pg/mL) were slightly higher compared to normal subjects and sFas (3.7 +/- 1.2 versus 2.1 +/- 0.7 ng/mL) increased significantly. sFas (3.9 +/- 1.8), TNF-alpha (79.3 +/- 72.4), and IL-6 (234.1 +/- 135.2) in DHCM were significantly increased and only IL-6 was significantly different from HNCM. sFas-L (0.18 +/- 0.08 versus 0.25 +/- 0.05 ng/mL) in HNCM was significantly decreased, and the decrease was marked in DHCM (0.05 +/- 0.02). In HNCM, TNF-alpha was negatively correlated with fractional shortening (r = -0.432, P = 0.0062) or positively with IL-6 (r = 0.665, P < 0.0001), while sFas-L was negatively correlated with IL-6 (r = -0.580, P < 0.0001). DHCM with high sFas had significantly higher cumulative incidences of worsening heart failure. The Fas/Fas-L system and proinflammatory cytokines may play an important role in the status of HCM and its progression to DHCM.
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PMID:Analysis of circulating apoptosis mediators and proinflammatory cytokines in patients with idiopathic hypertrophic cardiomyopathy: comparison between nonobstructive and dilated-phase hypertrophic cardiomyopathy. 1587 7


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