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)

Atrial fibrillation (AF) is a major cause of morbidity and mortality from stroke due to thromboembolism from the fibrillating left atrium, including its appendage. We hypothesized that indexes of inflammation (as indicated by C-reactive protein and interleukin-6) and indexes of the prothrombotic state in AF that represent platelet activation (soluble P-selectin levels), endothelial damage or dysfunction (von Willebrand factor), coagulation (tissue factor and fibrinogen), and hemorrheology (plasma viscosity and hematocrit) would be related to the presence of thromboembolic predictors on transesophageal echocardiography in patients with long-term AF. To test this hypothesis, we recruited 37 patients with long-term AF who were receiving warfarin therapy with an international normalized ratio of > or =2.0 for > or =3 weeks before transesophageal echocardiography. Twenty-two patients had dense spontaneous echo contrast (SEC) visible in the left atrium or left atrial appendage, 10 had complex atheromatous plaque in the descending aorta, 11 had peak left atrial appendage velocities < or =0.2 m/s, and 3 had thrombus visible in the left atrial appendage. Twenty-eight patients had > or =1 transesophageal echocardiographic (TEE) risk factor for thromboembolism. Plasma levels of C-reactive protein (p = 0.03) and soluble P-selectin (p = 0.04) and hematocrit (p = 0.004) were higher among patients with AF with dense SEC than among those without. No significant associations were found for other TEE risk factors. Hematocrit was the only variable significantly associated with the presence of > or =1 TEE risk factor among patients with AF (p = 0.007) and the only independent associate of dense SEC after multivariate analysis (relative risk 1.4, 95% confidence interval 1.1 to 1.6) per 1% increase in hematocrit (p = 0.003, r(2) = 0.22). Although hematocrit was the only independent associate of dense SEC and > or =1 TEE risk factor, significant associations between dense SEC and the 2 indexes, C-reactive protein and soluble P-selectin, may indicate that mechanisms other than stasis are present with dense SEC. These observations support an "inflammatory hypothesis" in the pathogenesis of SEC that may have implications for thrombogenesis in AF.
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PMID:Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation. 1516 16

Several evidences, ranging from in vitro experiments, pathologic analysis and epidemiologic studies, show that atherosclerosis is intrinsically an inflammatory disease. The plasma concentrations of interleukin-6 (IL-6) and its hepatic by-product, C-Reactive Protein (CRP), appear to reflect the intensity of occult plaque inflammation and by inference may determine the vulnerability of plaque rupture. The monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in initiating coronary artery disease by recruiting monocytes/macrophages to the vessel wall. This leads to the formation of atherosclerotic lesions and also increases the vulnerability of the plaque. Indeed, circulating IL-6 and MCP-1 levels are elevated in patients with acute myocardial infarction, and also in patients with unstable angina, but not in those with stable angina. The plasma IL-6 and MCP-1 concentrations are also increased after percutaneous coronary intervention (PCI), and late restenosis is correlated with an increase in IL-6 or MCP-1 concentrations after the procedure. This finding suggests that the expression of IL-6 and MCP-1 may not only be related to the instability of atheromatous plaques, but also to the formation of restenotic lesions after PCI. The development of drugs specifically targeted against IL-6 and MCP-1 may be useful in the prevention of plaque formation, myocardial infarction and restenosis.
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PMID:Inflammation and coronary artery disease. 1532 Aug 54

Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis and mediate the stages of atheroma development from initial leukocyte recruitment to eventual rupture of the unstable atherosclerotic plaque. Recent investigations demonstrated that several inflammatory markers are considered as new predictable risk factors for atherosclerosis and cardiac events. Among these markers, C-reactive protein (CRP) has been most widely studied. CRP is produced in the liver in response to interleukin-6 (IL-6), it is an acute phase reactant and used as a general inflammatory marker. High-sensitivity-CRP (hs-CRP) which could detect a small amount of CRP was recently developed, and numerous large-scale, prospective studies have found that elevated baseline levels of hs-CRP are independent predictor of cardiovascular events. Inflammatory cytokines such as IL-6 and tumor necrosis factor-alpha (TNF-alpha) have also been evaluated as potential tools for prediction of the cardiovascular events. In this review, we focused on the recent reports and potential use of the inflammatory markers and cytokines as a predictable tool for the cardiovascular events.
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PMID:[Inflammatory markers and cytokines in cardiovascular disease]. 1547 24

Inflammation within coronary plaques may cause an acute coronary syndrome by promoting rupture and erosion. It was the aim of this study to examine whether markers of inflammation derive from a cardiac or extracardiac source and how their levels develop over time. Blood samples were taken from patients with acute coronary syndromes (ACS) with proven atherosclerotic lesion(s) of the left coronary artery (n=13) and from control patients without coronary artery disease (n=13). Blood was taken from the femoral vein and the coronary sinus vein before and after coronary angioplasty (day 0) and on days 1 and 120. Levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1-receptor antagonist (IL-1 ra) and soluble CD40 ligand (sCD40L) were higher in ACS patients as compared to controls and remained elevated up to day 120. In the long-term time course these markers of inflammation and plaque remodeling slightly decreased in ACS patients. There were no statistically significant differences detectable in the levels of TNF-alpha, IL-6, IL-1 beta, IL-10, IL-1 ra, sCD40L and monocyte chemoattractant protein-1 (MCP-1) in the blood of ACS patients taken from a cardiac source as compared to an extracardiac source (coronary sinus vs. femoral vein). This study demonstrates the importance of a systemic inflammatory condition in patients with ACS, in whom markers of inflammation are increased as compared to controls. During long-term follow-up the pro-inflammatory activity remains elevated in ACS patients, supporting the concept of a systemic rather than a local vascular inflammation contributing to the development of atherosclerosis.
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PMID:Time course of systemic markers of inflammation in patients presenting with acute coronary syndromes. 1555 72

The principles of Virchov's triad appear to be operational in atherothrombosis or arterial thrombosis: local flow changes and particularly vacular wall damage are the main pathophysiological elements. Furthermore, alterations in arterial blood composition are also involved although the specific role and importance of blood coagulation is an ongoing matter of debate. In this review we provide support for the hypothesis that activated blood coagulation is an essential determinant of the risk of atherothrombotic complications. We distinguish two phases in atherosclerosis: In the first phase, atherosclerosis develops under influence of "classical" risk factors, i.e. both genetic and acquired forces. While fibrinogen/fibrin molecules participate in early plaque lesions, increased activity of systemic coagulation is of no major influence on the risk of arterial thrombosis, except in rare cases where a number of specific procoagulant forces collide. Despite the presence of tissue factor - factor VII complex it is unlikely that all fibrin in the atherosclerotic plaque is the direct result from local clotting activity. The dominant effect of coagulation in this phase is anticoagulant, i.e. thrombin enhances protein C activation through its binding to endothelial thrombomodulin.The second phase is characterized by advancing atherosclerosis, with greater impact of inflammation as indicated by an elevated level of plasma C-reactive protein, the result of increased production influenced by interleukin-6. Inflammation overwhelms protective anticoagulant forces, which in itself may have become less efficient due to down regulation of thrombomodulin and endothelial cell protein C receptor (EPCR) expression. In this phase, the inflammatory drive leads to recurrent induction of tissue factor and assembly of catalytic complexes on aggregated cells and on microparticles, maintaining a certain level of thrombin production and fibrin formation. In advanced atherosclerosis systemic and vascular wall driven coagulation becomes more important and elevated levels of D-dimer fragments should be interpreted as markers of this hypercoagulability.
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PMID:Blood coagulation and the risk of atherothrombosis: a complex relationship. 1557 98

Inflammation plays a pivotal role in atherosclerosis and coronary heart disease. Inflammatory processes of the coronary arterial wall are involved in plaque formation, progression and, finally, plaque instability consecutively leading to the clinical manifestations of stable coronary artery disease or acute coronary syndromes (unstable angina, non-ST elevation and ST elevation myocardial infarction). Acute coronary syndromes result from plaque rupture or erosion leading to local thrombus formation with consecutive necrosis of myocytes due to ischemia, which is associated with widespread and diffuse pancoronary and panmyocardial inflammation. Accordingly, markers of myocardial necrosis (e. g., cardiac troponins) do have crucial diagnostic and prognostic value. In case of troponin-negative acute coronary syndromes, however, markers of inflammation emerged as potentially useful tools for risk stratification. C-reactive protein has been shown to serve as a powerful predictor of future cardiovascular events following acute coronary syndromes, even if troponins are not (yet) positive. Moreover, a variety of pro- (soluble CD40 ligand, placental growth factor, interleukin-6, pregnancy-associated plasma protein A, myeloperoxidase, monocyte chemoattractant protein-1) and anti-inflammatory markers (interleukin-10, activin A) have been suggested to provide relevant prognostic information in patients with acute coronary syndrome. However, the clinical utility of these novel markers has not been established so far.
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PMID:[Acute coronary syndrome and inflammation. Biomarkers for diagnostics and risk stratification]. 1559 73

Environmental factors, including cigarette smoke components, can cross the placental barrier and accumulate in amniotic fluid and fetal tissue, and, therefore, interfere with the normal course of ontogenesis. Although cigarette smoke contains numerous compounds, the most adverse effects on mammalian tissues have been associated with nicotine. The aim of this study was to investigate the effect of intrauterine exposure to nicotine on hematopoiesis during fetal development and postpartum. Intrauterine exposure of mice to nicotine resulted in a more than two-fold reduction of the delayed- type hypersensitivity (DTH) response and a 2.5-fold decrease in the number of plaque forming cell (PFC) in offspring after 1 month of postnatal life, and correlated with low counts of mature lymphocytes and lymphoid progenitors in hematopoietic tissues. Neonates exposed to nicotine during gestation showed a significant decrease in the number of bone marrow hematopoietic progenitors, as measured by colony-forming unit (CFU) and long-term culture initiating cell (LTC-IC) assays, and decreased concentration of interleukin-6 (IL-6) in their serum. Analysis of the fetal bone marrow (E15) obtained from nicotine-exposed fetuses demonstrated a lower number of hematopoietic progenitors, whereas their number in the fetal liver was not significantly changed. Our data provide evidence that by targeting the nicotinic acetylcholine receptor (nAChR) nicotine interferes with the fetal development of the hematopoietic system. Inferior colonization of the fetal bone marrow by hematopoietic stem/progenitor cells (HSPC) subsequently results in an imbalance of mature blood and immune cell production after birth.
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PMID:Exposure to nicotine during gestation interferes with the colonization of fetal bone marrow by hematopoietic stem/progenitor cells. 1572 47

CEP-1347 is a potent inhibitor of the mixed lineage kinases (MLKs), a distinct family of mitogen-activated protein kinase kinase kinases (MAPKKK). It blocks the activation of the c-Jun/JNK apoptotic pathway in neurons exposed to various stressors and attenuates neurodegeneration in animal models of Parkinson's disease (PD). Microglial activation may involve kinase pathways controlled by MLKs and might contribute to the pathology of neurodegenerative diseases. Therefore, the possibility that CEP-1347 modulates the microglial inflammatory response [tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1)] was explored. Indeed, the MLK inhibitor CEP-1347 reduced cytokine production in primary cultures of human and murine microglia, and in monocyte/macrophage-derived cell lines, stimulated with various endotoxins or the plaque forming peptide Abeta1-40. Moreover, CEP-1347 inhibited brain TNF production induced by intracerebroventricular injection of lipopolysaccharide in mice. As expected from a MLK inhibitor, CEP-1347 acted upstream of p38 and c-Jun activation in microglia by dampening the activity of both pathways. These data imply MLKs as important, yet unrecognized, modulators of microglial inflammation, and demonstrate a novel anti-inflammatory potential of CEP-1347.
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PMID:Inhibition of microglial inflammation by the MLK inhibitor CEP-1347. 1574 62

BACKGROUND: Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS. METHODS: The FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest. CONCLUSION: The primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins.
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PMID:Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696]. 1579 Apr 13

Tumor embolism occurs in 30 to 50% of all cases of cardiac myxoma, but the causes are still uncertain. Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the extracellular matrix (ECM) and play a crucial role in plaque instability and aortic aneurysm development, in addition to cancer and heart failure. To determine whether MMP activity contributes to tumor embolism, we examined 27 left atrium-sided myxomas, 10 of which showed clinical signs of peripheral embolism. Immunohistochemistry (in all cases) and Western blotting, and in situ and in-gel zymography (in four embolic and six nonembolic consecutive tumors) demonstrated higher expression and activity of MT1-MMP, pro-MMP-2, and pro-MMP-9 in embolic myxomas, whereas pro-MMP-1, MMP-3, and TIMP-1 levels were similar to those of nonembolic tumors. Reverse transcriptase-polymerase chain reaction demonstrated that increased MMP activity was due, at least in part, to increased transcription and that TIMP-2 transcripts increased in embolic myxomas. In vitro, embolic tumor cells retained higher MT1-MMP and pro-MMP-2 levels in basal conditions and after stimulation with interleukin-1beta and interleukin-6. Increased MMP synthesis and release correlated with enhanced ECM degradation products containing glycosaminoglycan chains in embolic myxoma tissue. Our results strongly suggest that MMP overexpression may contribute to an excessive degradation of tumor ECM and increase the risk of embolism in cardiac myxomas.
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PMID:Increased expression and activity of matrix metalloproteinases characterize embolic cardiac myxomas. 1592 Jan 47

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