UNIPROT:P05231 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Anemia is found in about one-third of all cases of congestive heart failure (CHF). The most likely common cause is chronic kidney insufficiency (CKI), which is present in about half of all CHF cases. The CKI is likely to be due to the renal vasoconstriction that often accompanies CHF and can cause long-standing renal ischemia. This reduces the amount of erythropoietin (EPO) produced in the kidney and leads to anemia. However, anemia can occur in CHF without CKI and is likely to be due to excessive cytokine production (for example, tumor necrosis factor-alfa (TNF-alfa) and interleukin-6 (IL-6)), which is common in CHF and can cause reduced EPO secretion, interference with EPO activity in the bone marrow and reduced iron supply to the bone marrow. The anemia itself can worsen cardiac function, both because it causes cardiac stress through tachycardia and increased stroke volume, and because it can cause a reduced renal blood flow and fluid retention, adding further stress to the heart. Long-standing anemia of any cause can cause left ventricular hypertrophy (LVH), which can lead to cardiac cell death through apoptosis and worsen the CHF. Therefore, a vicious circle is set up wherein CHF causes anemia, and the anemia causes more CHF and both damage the kidneys worsening the anemia and the CHF further. We have termed this vicious circle the cardio renal anemia (CRA) syndrome. Patients with CHF who are anemic are often resistant to all CHF medications resulting in being hospitalized repeatedly. Many studies also demonstrate that these patients die more rapidly than their non-anemic counterparts do. In addition, they have a more rapid deterioration in their renal function and can end up on dialysis. There is now evidence from both uncontrolled and controlled studies that early correction of the CHF anemia with subcutaneous EPO and intravenous (i.v.) iron improves shortness of breath and fatigue, cardiac function, renal function and exercise capability, dramatically reducing the need for hospitalization. For these reasons, it is not surprising that quality of life has also been shown to improve. As both CHF and end-stage renal disease (ESRD) are rapidly increasing, the possibility that these twin conditions can be improved by the adequate treatment of anemia offers new hope for slowing the progression of both conditions.
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PMID:The role of anemia in the progression of congestive heart failure. Is there a place for erythropoietin and intravenous iron? 1559 47

Inflammation and endothelial dysfunction play important roles in the pathophysiology of congestive heart failure (CHF), and the peptide bradykinin, generated during inflammation, may act as a defence mechanism by inducing vasodilation. Plasma bradykinin levels are increased in experimental heart failure but low in patients with advanced chronic CHF despite treatment with angiotensin-converting enzyme (ACE) inhibitors. It is not currently known how bradykinin behaves in less severe phases of CHF controlled by long-term ACE inhibitor treatment. We studied 10 male patients with clinically stable chronic CHF [New York Heart Association (NYHA) class II] on long-term ACE inhibitor treatment and 10 normal sex- and age-matched control subjects. High performance liquid chromatography/radioimmunoassay methods were used to evaluate plasma levels of bradykinin in relation to an array of parameters of endothelial function, coagulation and inflammation before and after stimuli of forearm arterial occlusion and physical exercise. CHF patients had higher levels of bradykinin (P = 0.008), activated factor XII (P = 0.049), interleukin-6 (P = 0.050) and tumour necrosis factor receptor II (sTNFRII) (P = 0.026) than controls. Arterial occlusion and exercise significantly increased bradykinin and von Willebrand factor levels in controls but not in CHF patients. The increase in brachial artery diameter after arterial occlusion was less in CHF patients (P = 0.036) and inversely related to baseline plasma levels of bradykinin (r = -0.855, P = 0.002) and sTNFRII (r = -0.780, P = 0.008). NYHA class II CHF patients during long-term treatment with ACE inhibitors have increased bradykinin levels and signs of inflammation. They are unable to respond adequately to stimuli of ischaemia and physical exercise which both require vasodilation.
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PMID:Impaired bradykinin response to ischaemia and exercise in patients with mild congestive heart failure during angiotensin-converting enzyme treatment. Relationships with endothelial function, coagulation and inflammation. 1598 53

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index <0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [OR(integral)] = 1.34, 95% confidence interval [CI] 1.10-1.63; OR(trabecular )= 1.25, 95% CI 1.02-1.53; OR(cortical )= 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.
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PMID:Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the health, aging, and body composition study. 1692 45

Congestive heart failure (CHF) induces a state of immune activation, and peritoneal macrophages (M phi s) may play an important role in the development and progression of one such condition. Moderate endurance training modulates peritoneal M phi function. We evaluated the effect of endurance training on different stages of the phagocytic process and in the production of interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) after LPS stimulation. Either ligation of the left coronary artery or Sham operations were performed in adult Wistar rats. After 4 wk, control (Sham operated) and MI (ligation of the left coronary artery) animals were randomly assigned to either a sedentary (Sham-operated sedentary, n = 7 and MI sedentary, n = 10) or a trained group (Sham-operated trained, n = 8 and MI trained, n = 8). Trained rats ran on a treadmill (0% grade at 13-20 m/min) for 60 min/day, 5 days/wk, for 8-10 wk, whereas sedentary rats had only limited activity. Training increased maximal oxygen uptake normalized for body weight (ml.kg(-1).min(-1)), as well as skeletal muscle citrate synthase maximal activity, when compared with sedentary groups. The resident and total cell number, the chemotaxis index, and the production of TNF-alpha stimulated by LPS were significantly higher in the MI sedentary group when compared with the Sham sedentary group. Moderate endurance training reversed these alterations promoted by post-MI. These results demonstrate that moderate intensity exercise training modulates peritoneal M phi function and induces beneficial metabolic effects in rats with post-MI CHF.
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PMID:Endurance training restores peritoneal macrophage function in post-MI congestive heart failure rats. 1725 73

Acute-phase markers, such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), have been studied in inflammatory and malignant disorders. We examined the diagnostic value of these markers for the differentiation among parapneumonic, tuberculous and malignant effusions. We studied 124 patients with pleural effusions, classified as exudates [total (n=97), parapneumonic (n=15), tuberculous (n=25), malignant (n=57)] and transudates due to congestive heart failure (n=27). CRP, IL-6 and TNF-alpha were measured in pleural fluid and serum. Pleural fluid CRP was higher in parapneumonic compared to tuberculous and malignant effusions, providing 100% sensitivity for a cut-off point of 5.3mg/dL. IL-6 was higher in both parapneumonic and tuberculous compared to malignant effusions. TNF-alpha was higher in tuberculous compared to malignant effusions, providing 96.0% sensitivity, and 93.0% specificity for a cut-off point of 88.1 pg/mL. Pleural fluid CRP levels were lower than serum in all groups, probably reflecting systemic inflammation, whereas IL-6 and TNF-alpha were higher in pleural fluid indicating local production. Our data suggest that these markers may provide useful information for the differentiation of infectious and malignant effusions in clinical practice. However, further studies are needed for the validation of these findings in usual clinical circumstances.
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PMID:Acute phase markers for the differentiation of infectious and malignant pleural effusions. 1727 Apr 13

Complex clinical-laboratory investigation of children with congestive heart failure (CHF) developed on the basis of dilated cardiomyopathy and hypertrophic cardiomyopathy has been carried out. The development of CHF in children with cardiomyopathy was accompanied by changes of blood serum lactate, MB isoform of creatine phosphokinase, TNF-6, interleukin-6 (IL-6) (but not IL-2), and soluble receptors for IL-2 and IL-6.
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PMID:[Biochemical and immunological markers of insufficiency of blood circulation at children with cardiomiopathies]. 1763 21

Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia-reperfusion injury. Furthermore, ischemia-reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-alpha) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart.
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PMID:Role of cytokines in myocardial ischemia and reperfusion. 1847 18

Music therapy (MT) has been used in geriatric nursing hospitals, but there has been no extensive research into whether it actually has beneficial effects on elderly patients with cerebrovascular disease (CVD) and dementia. We investigated the effects of MT on the autonomic nervous system and plasma cytokine and catecholamine levels in elderly patients with CVD and dementia, since these are related to aging and chronic geriatric disease. We also investigated the effects of MT on congestive heart failure (CHF) events.Eighty-seven patients with pre-existing CVD were enrolled in the study. We assigned patients into an MT group (n = 55) and non-MT group (n = 32). The MT group received MT at least once per week for 45 minutes over 10 times. Cardiac autonomic activity was assessed by heart rate variability (HRV). We measured plasma cytokine and catecholamine levels in both the MT group and non-MT group. We compared the incidence of CHF events between these two groups. In the MT group, rMSSD, pNN50, and HF were significantly increased by MT, whereas LF/HF was slightly decreased. In the non-MT group, there were no significant changes in any HRV parameters. Among cytokines, plasma interleukin-6 (IL-6) in the MT group was significantly lower than those in the non-MT group. Plasma adrenaline and noradrenaline levels were significantly lower in the MT group than in the non-MT group. CHF events were less frequent in the MT group than in the non-MT group (P < 0.05). These findings suggest that MT enhanced parasympathetic activities and decreased CHF by reducing plasma cytokine and catecholamine levels.
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PMID:Effects of music therapy on autonomic nervous system activity, incidence of heart failure events, and plasma cytokine and catecholamine levels in elderly patients with cerebrovascular disease and dementia. 1924 50

Vascular inflammation is a common pathophysiological response to diverse cardiovascular disease processes, including atherosclerosis, myocardial infarction, congestive heart failure, and aortic aneurysms/dissection. Inflammation is an ordered process initiated by vascular injury that produces enhanced leucocyte adherence, chemotaxis, and finally activation in situ. This process is coordinated by local secretion of adhesion molecules, chemotactic factors, and cytokines whose expression is the result of vascular injury-induced signal transduction networks. A wide variety of mediators of the vascular injury response have been identified; these factors include vasoactive peptides (angiotensin II, Ang II), CD40 ligands, oxidized cholesterol, and advanced glycation end-products. Downstream, the nuclear factor-kappaB (NF-kappaB) transcription factor performs an important signal integration step, responding to mediators of vascular injury in a stimulus-dependent and cell type-specific manner. The ultimate consequence of NF-kappaB signalling is the activation of inflammatory genes including adhesion molecules and chemotaxins. However, clinically, the hallmark of vascular NF-kappaB activation is the production of interleukin-6 (IL-6), whose local role in vascular inflammation is relatively unknown. The recent elucidation for the role of the IL-6 signalling pathway in Ang II-induced vascular inflammation as one that controls monocyte activation as well as its diverse signalling mechanism will be reviewed. These new discoveries further our understanding for the important role of the NF-kappaB-IL-6 signalling pathway in the process of vascular inflammation.
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PMID:The nuclear factor-kappaB-interleukin-6 signalling pathway mediating vascular inflammation. 2020 75

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