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

The development and progression of atherosclerosis comprises various processes, such as endothelial dysfunction, chronic inflammation, thrombus formation, and lipid profile modification. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that have pleiotropic effects in addition to cholesterol-lowering properties. However, the mechanisms of these effects are not completely understood. Here, we investigated whether atorvastatin affects the levels of malondialdehyde-modified low-density lipoprotein (MDALDL), an oxidized LDL, the proinflammatory cytokine interleukin-6 (IL-6), or platelet P-selectin, a marker of platelet activation, relative to that of LDL cholesterol (LDL-C). Forty-eight patients with coronary artery disease and hyperlipidemia were separated into two groups that were administered with (atorvastatin group) or without (control group) atorvastatin. The baseline MDA-LDL level in all participants significantly correlated with LDL-C (r = 0.71, P < 0.01) and apolipoprotein B levels (r = 0.66, P < 0.01). Atorvastatin (10 mg/day) significantly reduced the LDL-C level within 4 weeks and persisted for a further 8 weeks of administration. Atorvastatin also reduced the MDA-LDL level within 4 weeks and further reduced it over the next 8 weeks. Platelet P-selectin expression did not change until 4 weeks of administration and then significantly decreased at 12 weeks, whereas the IL-6 level was gradually, but not significantly, reduced at 12 weeks. In contrast, none of these parameters significantly changed in the control group within these time frames. The reduction (%) in IL-6 between 4 and 12 weeks after atorvastatin administration significantly correlated with that of MDALDL and of platelet P-selectin (r = 0.65, P < 0.05 and r = 0.70, P < 0.05, respectively). These results suggested that the positive effects of atorvastatin on the LDL-C oxidation, platelet activation and inflammation that are involved in atherosclerotic processes are exerted in concert after lowering LDL-C.
 ...
PMID:Atorvastatin induces associated reductions in platelet P-selectin, oxidized low-density lipoprotein, and interleukin-6 in patients with coronary artery diseases. 1864 55

We investigated the effect of atorvastatin monotherapy and combined treatment with atorvastatin and pioglitazone on intima-media thickness, vascular function and the cardiovascular risk profile. In all, 148 patients (76 male, 72 female; aged 61.4+/-6.5 years; body mass index [BMI] 29.2+/-4.1 kg/m2; mean +/- SD) with increased cardiovascular (CV) risk factors were randomised. Intima-media thickness (IMT), the augmentation index (Aix@75), the microvascular response to acetylcholine (LDF), lipid status, and plasma levels of intact proinsulin, adiponectin, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), sCD40L, P-selectin, tissue plasminogen activator (t-PA) and blood lipids were monitored over six months. Atorvastatin treatment, alone and in combination with pioglitazone, revealed a significant regression in IMT (0.923+/-0.013 to 0.874+/-0.012 mm and 0.921+/-0.015 to 0.882+/-0.015 mm; mean +/- SEM; p<0.05 respectively) and Aix@75 (27.3+/-1.2 to 25.9+/-1.4; and 25.6+/-1.4 to 24.8+/-1.7%; p<0.05). The endothelial response to acetylcholine as measured by laser Doppler fluximetry (LDF) improved during combined treatment (373+/-57 to 576+/-153 AU; p<0.05). Addition of pioglitazone to atorva-statin resulted in significant further effects on high-sensitivity C-reactive protein (hsCRP), t-PA, P-selectin, adiponectin, triglycerides and high-density lipoprotein (HDL) cholesterol (p<0.05 respectively). Atorvastatin significantly improved IMT and vascular elasticity. Co-administration of pioglitazone provided additional effects on endothelial function, lipid profile and laboratory markers of inflammation.
 ...
PMID:Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk. 1895 40

The predisposition to thrombogenesis is increased in essential hypertension, and hypertensive patients are prone to develop more vulnerable atherosclerotic plaques. To evaluate the possible influence of family history of hypertension on some indicators of early atherosclerosis, we studied eighty-five healthy normotensive individuals with (FH+) or without (FH-) family history of essential hypertension by measuring metabolic profile and concentrations of P-selectin, interleukin 6 and matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1. In a subset of individuals, MMP-9 activity was assessed in monocytes by zymography, and TIMP-1 expression by western blot. As compared with FH- individuals, FH+ individuals had significantly higher P-selectin but similar interleukin-6 levels. Although no difference was observed in MMP-2 levels between the two groups, MMP-9 and TIMP-1 were higher in FH+ individuals, who also had higher intracellular MMP-9 levels and TIMP-1 protein expression. P-selectin (r=-0.32; P<0.01), MMP-9 (r=-0.37; P<0.001) and TIMP-1 (r=-0.23; P<0.05) levels were inversely related to high density lipoprotein (HDL) cholesterol. P-selectin was also directly related to serum triglycerides (r=0.30; P<0.01). We conclude that a positive family history of hypertension is associated with an initial increase in markers of inflammation and plaque instability in otherwise healthy young normotensive individuals, likely conveying a predisposition to develop early atherothrombosis.
 ...
PMID:Family history of hypertension, anthropometric parameters and markers of early atherosclerosis in young healthy individuals. 1933 95

Continuous exposure to nitroglycerin (GTN) results in development of tolerance and is associated with increased free radical production and abnormal endothelial function. Elevated plasma biomarkers of inflammation have been shown to be associated with endothelial dysfunction in most cardiovascular conditions. It remains unclear whether exposure to GTN is also associated with increased biomarkers of endothelial and vascular injury or vascular inflammation. In an investigator-blind study, a total of 28 healthy volunteers were randomized to continuous therapy with GTN (0.6 mg/h 24 h/day for 7 days) or no therapy. Venous blood was collected on day 0 and day 7. Plasma levels of markers such as asymmetric dimethyl-arginine (ADMA), human soluble P-selectin, interleukin-6, tumor necrosis factor-alpha, intercellular adhesion molecule-1, and oxidized low-density lipoproteins were measured. The levels of blood markers on day 0 were similar in the control and GTN-treated groups. After 7 days of GTN exposure, there were no significant changes in the different markers of vascular inflammation and injury either in the GTN or control group (all p > 0.5). The present study documents that prolonged continuous therapy with transdermal GTN therapy is not associated with changes in markers of vascular inflammation and injury.
 ...
PMID:Continuous therapy with transdermal nitroglycerin does not affect biomarkers of vascular inflammation and injury in healthy volunteers. 1952 40

Basic and clinical studies have suggested that inflammation predisposes to atrial fibrillation (AF). We assessed the association of 12 circulating inflammatory biomarkers (i.e., C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II) with incident AF in 2863 Framingham Offspring Study participants (mean age 60.7 years, SD = 9.4, 55% women). During follow-up (median 6 years), 148 participants (43% women) developed incident AF. In the multivariable proportional hazards models, the inflammatory biomarker panel was associated with incident AF (p = 0.03). With stepwise selection (p <0.01 for entry and retention), log-transformed osteoprotegerin was associated with incident AF (hazard ratio per SD 1.30, 95% confidence interval 1.08 to 1.56, p = 0.006). Adjusting for interim myocardial infarction or heart failure attenuated the association between osteoprotegerin and incident AF (hazard ratio 1.18, 95% confidence interval 0.98 to 1.43, p = 0.09). In conclusion, circulating osteoprotegerin concentration was significantly associated with incident AF in our community-based sample, possibly mediated by interim cardiovascular events.
 ...
PMID:Relation of multiple inflammatory biomarkers to incident atrial fibrillation. 1957 26

Although current H5N1 highly pathogenic avian influenza viruses (HPAIV) are inefficiently transmitted to humans, infected individuals can suffer from severe disease, often progressing rapidly to acute respiratory distress syndrome and multiorgan failure. This is in contrast with the situation with human influenza viruses, which in immunocompetent individuals usually cause only a respiratory disease which is less aggressive than that observed with avian H5N1 viruses. While the biological basis of inefficient transmission is well documented, the mechanisms by which the H5N1 viruses cause fatal disease remain unclear. In the present study, we demonstrate that human pulmonary microvascular endothelial cells (hPMEC) had a clearly higher susceptibility to infection by H5N1 HPAIV than to infection by human influenza viruses. This was measurable by de novo intracellular nucleoprotein production and virus replication. It was also related to a relatively higher binding capacity to cellular receptors. After infection of hPMEC, cell activation markers E-selectin and P-selectin were upregulated, and the proinflammatory cytokines interleukin-6 and beta interferon were secreted. H5N1 virus infection was also associated with an elevated rate of cell death. Reverse genetics analyses demonstrated a major role for the viral hemagglutinin in this cell tropism. Overall, avian H5N1 viruses have a particular receptor specificity targeting endothelial cells that is different from human influenza viruses, and this H5N1 receptor specificity could contribute to disease pathogenesis.
 ...
PMID:Hemagglutinin-dependent tropism of H5N1 avian influenza virus for human endothelial cells. 1981 46

The objective of this study was to determine whether systemic inflammatory and oxidative stress marker concentrations correlate with pericardial and intrathoracic fat volumes. Participants of the Framingham Offspring Study (n = 1,175, 53% women, mean age 59 +/- 9 years) had pericardial and intrathoracic fat volumes assessed by multidetector computed tomography (MDCT) scans, and provided fasting blood and urine samples to measure concentrations of 14 inflammatory markers: C-reactive protein (CRP), interleukin-6, monocyte chemoattractant protein-1 (MCP-1), CD40 ligand, fibrinogen, intracellular adhesion molecule-1, lipoprotein-associated phospholipase A(2) activity and mass, myeloperoxidase, osteoprotegerin, P-selectin, tumor necrosis factor-alpha, tumor necrosis factor receptor-2, and urinary isoprostanes. Multivariable linear regression models were used to determine the association of log-transformed inflammatory marker concentrations with fat volumes, using fat volume as the dependent variable. Due to smaller sample sizes, models were rerun after adding urinary isoprostanes (n = 961) and tumor necrosis factor-alpha (n = 813) to the marker panel. Upon backward elimination, four of the biomarkers correlated positively with each fat depot: CRP (P < 0.0001 for each fat depot), interleukin-6 (P < 0.05 for each fat depot), MCP-1 (P < 0.01 for each fat depot), and urinary isoprostanes (P < 0.01 for pericardial fat; P < 0.001 for intrathoracic fat). Even after adjusting for BMI, waist circumference (WC), and abdominal visceral fat, CRP (P = 0.0001) and urinary isoprostanes (P = 0.02) demonstrated significant positive associations with intrathoracic fat, but not with pericardial fat. Multiple markers of inflammation and oxidative stress correlated with pericardial and intrathoracic fat volumes, extending the known association between regional adiposity and inflammation and oxidative stress.
 ...
PMID:Pericardial fat volume correlates with inflammatory markers: the Framingham Heart Study. 1987 99

Vascular intervention-induced neointimal formation is a major drawback for managing atherosclerotic cardiovascular diseases using invasive vascular procedures. Our previous studies demonstrated that hirulog-like peptide (HLP) reduced balloon catheter dilation-induced neointimal formation or restenosis in carotid arteries of rats or atherosclerotic rabbits with less interruption in coagulation or bleeding than heparin or hirulog-1. The present study examined the effect of HLP on balloon catheter injury-induced neointimal formation in femoral arteries of minipigs. Intravenous infusion of HLP (1.6 mg/kg/h for 4 h started 0.5 h before the intervention) or unfractured heparin (50 U/kg/h for 4 h) significantly reduced neointimal formation in femoral arteries 4 weeks after intervention compared with the vehicle. Heparin, but not HLP, significantly prolonged activated partial thromboplastin time. HLP or heparin significantly reduced vascular intervention-induced increases in C-reactive protein, P-selectin and interleukin-6 in serum. HLP, but not heparin, normalized vascular injury-induced increase in P-selectin in platelets. The results of the present study suggest that HLP is an effective agent for preventing balloon catheter injury-induced neointimal formation in femoral arteries of minipigs. The beneficial effects of HLP on vascular injury-induced neointimal formation may partially result from its inhibition on inflammatory mediators.
 ...
PMID:Effect of hirulog-like peptide on balloon catheter injury-induced neointimal formation in femoral arteries of minipigs and relationship with inflammatory mediators. 1990 88

This study investigated the relationship between hyperuricemia (HUC) and the components of the metabolic syndrome (MS) among elderly institutionalized men. In addition, this study explored the relationship between HUC and serum inflammatory markers. A total of 333 participants from Chang-Hua Veterans Care Home were enrolled. The MS was defined using a modified ATP III definition issued in 2004 by the Bureau of Health Promotion, Department of Health, ROC (Taiwan). The participants' mean age was 78.6+/-3.9 years, and their mean serum uric acid level was 6.9+/-1.7 mg/dl. The prevalence of HUC was 46.2% (n = 154). The prevalence of the MS was 38.4% (n = 128). HUC was correlated with components of the MS, including waist circumference (WC), triglyceride (TG), and high density lipoprotein cholesterol (HDL-C) but it was not related to blood pressure (BP) and fasting plasma glucose (FPG). Moreover, increased serum creatinine, albumin, prealbumin, and body fat were also associated with HUC. The plasma activator inhibitor-1 (PAI-1) levels were significantly elevated in the HUC group, but serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), serum intercellular cell adhesion molecule-1 (sICAM-1), serum levels of vascular cell adhesion molecule-1 (sVCAM-1), and P-selectin were not related to HUC. HUC in elderly men may represent poorer renal function, better nutritional status, and increased body fat.
 ...
PMID:Relationship between hyperuricemia (HUC) and metabolic syndrome (MS) in institutionalized elderly men. 2000 27

Platelets have been shown to be important in inflammation, but their role in the cutaneous Arthus reaction remains unclear. To assess the role of platelets in this pathogenetic process, the cutaneous Arthus reaction was examined in wild-type mice and mice lacking E-selectin, P-selectin, or P-selectin glycoprotein ligand-1 (PSGL-1) with or without platelet depletion by busulfan, a bone marrow precursor cell-specific toxin. Edema and hemorrhage induced by immune complex challenge significantly decreased in busulfan-treated wild-type mice compared with untreated mice. Busulfan treatment did not affect edema and hemorrhage in P-selectin- or PSGL-1-deficient mice, suggesting that the effect by busulfan is dependent on P-selectin and PSGL-1 expression. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells and reduced levels of circulating platelets. Increased cutaneous production of interleukin-6, tumor necrosis factor-alpha, and platelet-derived chemokines during Arthus reaction was inhibited in busulfan-treated wild-type mice relative to untreated mice, which paralleled the reduction in cutaneous inflammation. Flow cytometric analysis showed that immune complex challenge generated blood platelet-leukocyte aggregates that decreased by busulfan treatment. In thrombocytopenic mice, the cutaneous inflammation after immune complex challenge was restored by platelet infusion. These results suggest that platelets induce leukocyte recruitment into skin by forming platelet-leukocyte aggregates and secreting chemokines at inflamed sites, mainly through the interaction of P-selectin on platelets with PSGL-1 on leukocytes.
 ...
PMID:Platelets control leukocyte recruitment in a murine model of cutaneous arthus reaction. 2000 31


<< Previous 1 2 3 4 5 6 7 8 9 Next >>