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)

Atherosclerosis, and the resulting coronary heart disease and stroke, is the most common cause of death in developed countries. Atherosclerosis is an inflammatory process that results in the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction (MI) and stroke. Although certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers of plaque vulnerability (C-reactive protein, interleukin-6, 10 and 18, CD40L) have been identified, a highly sensitive and specific biomarker or protein profile, which could provide information on the stability/vulnerability of atherosclerotic lesions, remains to be identified. In this review, we report several proteomic approaches which have been applied to circulating or resident cells, atherosclerotic plaques or plasma, in the search for new proteins that could be used as cardiovascular biomarkers. First, an example using a differential proteomic approach (2-DE and MS) comparing the secretome from control mammary arteries and atherosclerotic plaques is displayed. Among the different proteins identified, we showed that low levels of HSP-27 could be a potential marker of atherosclerosis. Second, we have revised several studies performed in cells involved in the pathogenesis of atherosclerosis (foam cells and smooth muscle cells). Another approach consists of performing proteomic analysis on circulating cells or plasma, which will provide a global view of the whole body response to atherosclerotic aggression. Circulating cells can bear information reflecting directly an inflammatory or pro-coagulant state related to the pathology. As an illustration, we report that circulating monocytes and plasma in patients with acute coronary syndromes has disclosed that mature Cathepsin D is increased both in the plasma and monocytes of these patients. Finally, the problems of applying proteomic approach directly to plasma will be discussed. The purpose of this review is to provide the reader with an overview of different proteomic approaches that can be used to identify new biomarkers in vascular diseases.
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PMID:Quest for novel cardiovascular biomarkers by proteomic analysis. 1608 68

The aim of the present study was to explore the relationship between tissue levels of leptin, soluble interleukin-6 receptor (sIL-6R), high-sensitive-C-reactive protein (hs-CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in atherosclerotic plaques, and traditional risk factors. Coronary artery specimens were obtained from 35 consecutive patients (26 men and nine women) who underwent coronary artery bypass grafting procedure. The mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in patients with diabetes mellitus than without diabetes mellitus. When patients were classified according to the smoking status, the mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in current smokers than both former smokers and non-smokers. In addition, the mean tissue levels of leptin and sIL-6R were significantly higher in former smokers than non-smokers. There was a positive association between leptin and hs-CRP, sIL-6R and plasma glucose in all patients. Plasma HDL levels were associated negatively with atherosclerotic tissue levels of leptin. Tissue levels of sIL-6R were associated significantly in a positive manner with leptin, hs-CRP and plasma glucose, while tissue levels of hs-CRP were associated with both leptin and sIL-6R. In conclusion, it is attractive to speculate that hs-CRP, sIL-6R and leptin could act synergistically in course of local inflammatory activity and those molecules may not be just markers of inflammation and cardiovascular risk but are also likely to play a pathogenic role in atheromatous plaque. In addition, atherosclerotic tissue levels of CRP, sIL-6R and leptin were significantly higher in current smokers and patients with diabetes.
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PMID:Leptin, soluble interleukin-6 receptor, C-reactive protein and soluble vascular cell adhesion molecule-1 levels in human coronary atherosclerotic plaque. 1648 44

The plasma levels of inflammatory cytokine interleukin-6 (IL-6) and anti-inflammatory cytokine interleukin-10 (IL-10) in the patients with unstable angina or stable angina were determined and compared. In 30 patients with unstable angina and 22 patients with stable angina, plasma levels of IL-10 and IL-6 were detected by ELISA and plasma lipid parameters by lipid research clinical methods respectively. The results showed plasma levels of IL-10 were significantly lower in unstable angina group than in stable angina group (P = 0.005), while those of IL-6 were significantly increased in unstable angina group as compared with those in stable angina group (P = 0.039). There was a significantly negative correlation between IL-10 and IL-6 in patients with unstable angina (r = -0.41, P = 0.003). In the unstable angina group, IL-6 levels were obviously positively correlated with TC (r = 0.314, P = 0.023), but not with TG and HDL. There were no significant correlations between IL-10 and plasma lipid parameters. It was suggested that the decreased IL-10 and increased IL-6 might be associated with the atheromatous plaque stability and progression of coronary heart diseases. IL-10 may play an important role in preventing coronary vascular lesions.
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PMID:Plasma levels of the anti-inflammatory cytokine IL-10 and inflammatory cytokine IL-6 in patients with unstable angina. 1669 12

There are increasing evidences showing that inflammation participates in atherosclerosis. Therefore, the therapeutic use of anti-inflammatory agents should be considered. We have induced chronic, aseptic inflammation upon the injection of turpentine and tested the effect of dexamethasone on lipoprotein metabolism and, consequently, atherosclerosis in apolipoprotein E-deficient mice. Aseptic inflammation caused a significant decrease in hyperlipidemia. Treatment with dexamethasone elicited the opposite effect increasing hyperlipidemia through mechanisms related to the increase in the synthesis of triglyceride-rich lipoproteins. Changes in plasma lipids correlated with those observed in the size of atherosclerotic lesions. Our data suggest the presence of a common mechanism present in both observations and which is probably related to the cytokine secretion. Among the candidates, we chose to test the effect of interleukin-6 because it is involved in both processes, atherosclerosis and inflammation, and its expression is efficiently repressed by corticosteroids. The injection of recombinant interleukin-6 in our mice elicited the same effects observed in our model of inflammation. We conclude that manipulation of inflammation-related mechanisms modulates lipid homeostasis and development of atherosclerotic plaque in rodents.
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PMID:Manipulation of inflammation modulates hyperlipidemia in apolipoprotein E-deficient mice: a possible role for interleukin-6. 1681 11

Periodontal disease is an infectious disease initiated by microbial plaque, which accumulates on the tooth surface at the gingival margin and induces an inflammatory reaction. The function of the inflammatory process is to protect the host, however the process may also contribute to tissue destruction. Most individuals show gingival inflammation, but only a limited number suffer from periodontitis i.e. loss of attachment. Without treatment, periodontitis will result in tooth mobility and subsequent tooth mortality. Independent of ethnicity, 10%-15% of an adult population will develop severe periodontitis The aim of this thesis has been to analyse individuals at risk for periodontal disease. Four studies have been conducted in 2 different groups of individuals with: Recurrent periodontitis kept in a maintenance care program--studies I-III. Type 2 diabetes (T2D)--study IV. In study I, the clinicaleffect of local periodontitis treatment with an antibiotic gel was investigated. In study II, the microbiologicaleffect of periodontitis treatment with the same antibiotic gel as in study I was investigated. In study III, it was investigated whether the interleukin-l (IL-1alpha and beta) and interleukin-6 (IL-6) gene polymorphisms were associated with the susceptibility of chronic periodontitis. In study IV, the prevalence of periodontitis in individuals with T2D was investigated, together with the prevalence of diabetic complications in relation to periodontal disease. We also studied whether there was a difference in dental care habits and knowledge of oral health between T2D subjects with and without periodontal disease. In conclusion, this thesis did not find any significant clinical and microbiological differences between subjects with recurrent periodontal disease treated with a locally delivered metronidazole gel compared to a placebo gel. Neither could we find an association between genetic variants in the IL-lalpha, IL-beta and IL-6 genes in individuals with or without periodontal disease. The prevalence of severe periodontitis, according to radiographic criteria, was almost 20% in subjects with T2D. This was further confirmed by clinical parameters. T2D individuals with periodontal disease demonstrated a higher HbAlc level, a higher prevalence of cardiovascular complications and a higher proportion of smokers compared to periodontally healthy T2D subjects. Finally, T2D individuals seem to lack sufficient knowledge about oral health.
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PMID:Studies on periodontitis and analyses of individuals at risk for periodontal diseases. 1683 63

Serotonin (5-HT), a potent vasoconstrictor in the large cerebral arteries, is considered to play a key role in atherothrombosis and to be implicated in ischemic cerebrovascular events followed by delayed neuronal death. The present study aims at evaluating the relationship between plasma levels of 5-HT and vascular dementia (VaD) caused by stroke or atherosclerotic small vessel disease. Carotid artery intima-media thickness (IMT), plaques, plasma 5-HT levels and atherosclerotic parameters were determined in 20 patients with VaD and 40 age-matched controls. Age, gender, body mass index, systolic and diastolic blood pressure, fasting plasma glucose levels and serum levels of insulin, triglycerides, high-density lipoprotein cholesterol, leptin, adiponectin and interleukin-6 and plasma levels of plasminogen activator inhibitor-1 were not significantly different between the two groups. Serum levels of insulin-like growth factor-1 (IGF-1) were significantly lower in VaD patients than in controls. Plasma 5-HT levels, serum levels of hepatocyte growth factor (HGF), low-density lipoprotein (LDL) cholesterol and high-sensitive C-reactive protein (hs-CRP), max IMT and plaque frequency were significantly greater in VaD patients than in controls. There was a significant positive correlation of max IMT with 5-HT or HGF levels. Multiple logistic regression analysis revealed that increased plasma levels of 5-HT and carotid plaque prevalence had significantly independent association with VaD as compared with serum levels of IGF-1, HGF, LDL cholesterol and hs-CRP. These results suggest that increased plasma levels of 5-HT and carotid atherosclerotic plaques may be involved in the pathogenesis and progression of VaD.
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PMID:Impact of increased plasma serotonin levels and carotid atherosclerosis on vascular dementia. 1704 33

Angiotensin II (A-II), the major effector peptide of the renin angiotensin system potently accelerates progression of atherosclerosis. To investigate its effects on vascular inflammatory mechanisms, we elucidated vascular cytokine expression during early lesion development in A-II-infused atherosclerosis-prone LDLR-/- mice. Male LDLR-/- mice were placed on a "Western" high-fat diet for 4 weeks, followed by sham or A-II infusion for 7 weeks. Equal blood pressures and elevations in serum lipids were seen in both groups. Mice were sacrificed when significant A-II-induced plaque development was first detectable, aortae were explanted and culture media assayed for secreted cytokines. Nine cytokines were significantly induced with interleukin-6 (IL-6) being the most highly secreted. Local IL-6 production was confirmed by in situ mRNA hybridization and immunostaining, where the most abundant IL-6 was found in the aortic adventitia, with lesser production by the medial and intimal layers. Immunofluorescence colocalization showed IL-6 expression by fibroblasts and activated macrophages. Activation of downstream IL-6 signaling mediated by the Jak-STAT3 pathway was demonstrated by inducible phospho-Tyr705-STAT3 formation in the adventitia and endothelium (of IL-6+/+ mice only). These findings define cytokine profiles in the A-II infusion model and demonstrate that IL-6, produced by activated macrophages and fibroblasts in the adventitia, induces the Jak-STAT3 pathway during early A-II-induced atherosclerosis.
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PMID:Angiotensin II induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice. 1710 63

Atherosclerosis is one of the most common causes of death in developed countries. Atherosclerosis is an inflammatory process that results in the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction and stroke. Although certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers of plaque vulnerability (C-reactive protein, interleukin-6, -10 and -18, CD-40L) have been identified, a highly sensitive and specific biomarker or protein profile, which could provide information on the stability/vulnerability of atherosclerotic lesions, remains to be identified. Recently, we have described a novel strategy consisting in the proteomic analysis of proteins released by normal and atherosclerotic arterial walls in culture. This method enables harvesting of proteins that are only secreted by pathological or normal arterial walls. By focusing only on the secreted proteins found in the tissue culture media, there is an intended bias toward those molecules that would have a higher probability of later being found in plasma. Using this approach, we have shown that carotid atherosclerotic plaques cultured in vitro are able to secrete proteins, and also that a differential pattern of protein secretion of normal arteries vs pathological ones has been observed. In this chapter, the proteomic analysis of the human atheroma plaque secretome is described.
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PMID:Characterization of the human atheroma plaque secretome by proteomic analysis. 1717 85

Stroke is the second cause of mortality in industrialized countries. Atherosclerotic plaque rupture with atheromatous debris distal embolization is the pathogenetic mechanism responsible for cerebrovascular events due to atherosclerotic carotid disease. Plaque composition rather than lesion burden seems to be the determinant factor producing rupture and subsequent thrombosis. Histologic features of vulnerability are : a large lipid core, a thin fibrous cap, and an inflammatory infiltrate rich of monocytes and macrophages. In the clinical practice, it is difficult to predict the risk of experiencing a major cerebrovascular events especially in asymptomatic patients. New invasive techniques such as intravascular ultrasound with termography, optical coherence tomography, fotons spectroscopy and elastography have been developed to detect atherosclerotic lesion tissue composition. However, such techniques are difficult to apply on a large scale basis in primary prevention. On the contrary, new serologic biomarkers such as Pregnancy Associated Plasma Protein-A, Lp-PLA2, Interleukin-6, Interleukin-12, metalloproteinases, lipoprotein-(a), and plaque oxidative products have been recently proposed for screening general and high risk population. The present paper will briefly review the current histologic characteristics of vulnerable plaque and the new imaging tools proposed for its detection, focusing on the most recent serologic biomarkers evaluated in the clinical practice to increase our accuracy in predicting not only the plaque but moreover the patient at risk for an acute cerebrovascular event.
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PMID:From carotid plaque biology to serologic markers of vulnerability to predict the risk of cerebrovascular events. 1751 60

Plasminogen activator inhibitor-1 (PAI-1) plays a pivotal role in the regulation of the fibrinolytic system and in the modulation of extracellular proteolysis. Increased PAI-1 was found in atherosclerotic lesions, and high PAI-1 plasma levels were associated with coronary heart disease. Smooth muscle cells (SMC) are a major source of PAI-1 within the vascular wall, and PAI-1 was implicated in SMC migration, proliferation, and apoptosis. We treated human coronary artery SMC (HCASMC) and human aortic SMC (HASMC) with the glycoprotein 130 (gp130) ligands cardiotrophin-1, interleukin-6 (IL-6), leukemia inhibitory factor (LIF), or oncostatin M (OSM). Only OSM increased PAI-1 antigen and activity production significantly in these cells up to 20-fold. OSM upregulated mRNA specific for PAI-1 up to 4.5-fold in these cells. HCASMC and HASMC express gp130, OSM receptor, IL-6 receptor, and LIF receptor. OSM induced extracellular signal-regulated kinase (ERK) 1/2 and Akt phosphorylations in HASMC. A phosphatidylinositol 3-kinase inhibitor and a mitogen-activated protein/extracellular signal-regulated kinase inhibitor reduced Akt and ERK1/2 phosphorylation, respectively, and abolished OSM-induced PAI-1 upregulation. A janus kinase/signal transducer and activator of transcription inhibitor, a p38 mitogen-activated protein kinase inhibitor, or c-Jun NH(2)-terminal kinase inhibitor I did not inhibit the OSM-dependent PAI-1 induction. OSM enhanced proliferation of both HCASMC and HASMC by 77 and 90%, respectively. We hypothesize that, if the effect of OSM on PAI-1 expression in smooth muscle cells is operative in vivo, it could, via modulation of fibrinolysis and extracellular proteolysis, be involved in the development of vascular pathologies such as plaque progression, destabilization and subsequent thrombus formation, and restenosis and neointima formation.
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PMID:The inflammatory cytokine oncostatin M induces PAI-1 in human vascular smooth muscle cells in vitro via PI 3-kinase and ERK1/2-dependent pathways. 1760 27


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