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)

In the present study, we tested the protective effect of 3,4,5,6-tetrahydroxyxanthone, a synthetic xanthone derivative, on myocardial ischemia-reperfusion injury in rats. Ischemia-reperfusion injury was induced by 30 min of global ischemia and 30 min of reperfusion in isolated rat hearts or 30 min coronary artery occlusion and 120 min reperfusion in vivo, respectively. Heart rate, coronary flow (CF), left ventricular pressure (LVP), and its first derivative (+/- dp/dt (max)) were recorded, and the activity of creatine kinase in coronary effluent and tumor necrosis factor-alpha (TNF-alpha) content in myocardial tissues were measured in vitro. The activity of serum creatine kinase, the level of TNF-alpha and interleukin-6 (IL-6), and myocardial infarct size were measured in vivo. 3,4,5,6-tetrahydroxyxanthone (30, 100 or 300 microM) caused a significant improvement of cardiac function (LVP and +/- dp/dt (max)) and a decrease in the release of creatine kinase in coronary effluent as well as the level of TNF-alpha in myocardial tissues in vitro. 3,4,5,6-tetrahydroxyxanthone (0.5 or 1.0 mg/kg, i.v.) also markedly decreased infarct size and the release of creatine kinase and TNF-alpha, and increased serum IL-6 level in vivo. These results suggest that 3,4,5,6-tetrahydroxyxanthone possesses a protective effect on myocardial ischemia-reperfusion injury, and that the protective effects of 3,4,5,6-tetrahydroxyxanthone may be related to inhibition of TNF-alpha production and stimulation of IL-6 generation by inhibition of ROS production.
Cardiovasc Drugs Ther 2004 Jul
PMID:3,4,5,6-Tetrahydroxyxanthone protects against myocardial ischemia-reperfusion injury in rats. 1536 25

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.
Curr Control Trials Cardiovasc Med 2005 Mar 24
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

The objective of this study was to investigate the effect of a specific endothelin-A receptor antagonist on mRNA expression of genes encoding vasoactive mediators and proinflammatory cytokines following complete vascular exclusion of the porcine liver. Fourteen adult German Landrace pigs were subjected to 120 minutes of warm hepatic ischemia by total vascular exclusion. The animals were divided into two groups: the control group received saline solution and the therapy group was given the selective endothelin-A receptor antagonist BSF 208075. Liver tissue samples were collected 1 hour after reperfusion and mRNA expression for preproendothelin-1, prointerleukin-1beta, prointerleukin- 6, pro-tumor necrosis factor-alpha and endothelial nitric oxide synthase was analyzed quantitatively using the TaqMan system. Additionally, immunohistochemical analysis using a semiquantitative score for endothelin-1 and endothelin-A receptor was performed. One hour after reperfusion, quantitative reverse transcriptase-polymerase chain reaction revealed significantly lower expression of preproendothelin-1, pro-tumor necrosis factor-alpha, and prointerleukin-6 in the therapy group compared to controls. Immunohistochemical analysis demonstrated significantly reduced endothelin-1 immunostaining after therapy. Treatment with the selective endothelin-A receptor antagonist exerts a protective effect on the microcirculation after liver ischemia and reperfusion. We were able to show that the endothelin-A receptor antagonist not only has effects on the expression of vasoactive genes, it also decreases gene expression of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6.
J Cardiovasc Pharmacol 2004 Nov
PMID:Changes of vasoregulatory gene expression following hepatic ischemia/reperfusion and treatment with endothelin-A receptor blockade. 1583 52

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.
Expert Rev Cardiovasc Ther 2005 Mar
PMID:Lifestyle modification and endothelial function in obese subjects. 1585 97

Chronic inflammation is common in hypertension and acts as an independent determinant of arterial blood pressure. Hypertensive patients are reported to have high circulating levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP). Recently, angiotensin II receptor blockers (ARBs) have been shown to possess benefits in addition to their ability to lower blood pressure, including anti-inflammatory and antioxidative properties within the vasculature. We evaluated the effects of the angiotensin II receptor blocker, valsartan, on these inflammatory cytokines. Thirty-nine patients with essential hypertension participated. These subjects received valsartan, 40 to 80 mg/day. Serum TNF-alpha, IL-6, CRP, and serum amyloid A (SAA) were measured before and after 3 months of treatment with valsartan. Valsartan significantly decreased systolic and diastolic blood pressure (160 +/- 16/92 +/- 11 mm Hg to 147 +/- 21/84 +/- 11 mm Hg, P = 0.001/P = 0.001, respectively). Serum TNF-alpha (9.1 +/- 8.6 pg/mL to 6.1 +/- 1.0 pg/mL, P = 0.006) and IL-6 (9.3 +/- 1.7 pg/mL to 8.9 +/- 1.4 pg/mL, P = 0.005) were significantly reduced after treatment with valsartan. However, C-reactive protein and serum amyloid A did not change. The angiotensin II receptor blocker, valsartan, may inhibit the development of atherosclerosis by lowering serum pro-inflammatory cytokines.
J Cardiovasc Pharmacol 2005 Dec
PMID:Effects of angiotensin II receptor blockade with valsartan on pro-inflammatory cytokines in patients with essential hypertension. 1630 95

The aim of the study was to investigate the influence of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on nonlipid effects of statins and fibrates in hypercholesterolemic subjects. C-reactive protein, homocysteine, adhesion molecules, CD40 ligand, interleukin-6 and monocyte chemoattractant protein-1 were measured prior to and following 30 days of simvastatin or fenofibrate therapy. Decreases in all the variables except for adhesion molecules and homocysteine were observed in both treatment groups, without genotype-related differences. Interestingly, fenofibrate treatment led to a significant increase in homocysteine levels (p = 0.03) only in carriers of the I allele. In conclusion, ACE genotype might help identify patients prone to this effect of fibrates.
Cardiovasc Drugs Ther 2006 Jun
PMID:The I allele of the angiotensin-converting enzyme gene polymorphism may determine an increase in homocysteine levels in fibrate-treated subjects. 1677 34

The present study examined the association of myocardial perfusion reserve index (MPRI) in cardiovascular magnetic resonance (CMR) with coronary microvascular dysfunction (CMD) and serum levels of markers of inflammation or endothelial activation. Twelve patients with typical angina pectoris without coronary artery disease were enrolled in this study, and CMR perfusion was analyzed using a steady-state-free-precession sequence with 3 short axis slices per heartbeat during first pass of 0.025 mmol Gadolinium-DTPA/kg body weight. The upslope of myocardial signal intensity curves was used to calculate MPRI. CMD was assessed by intracoronary Doppler flow measurement and biplane angiography. Both MPRI and CMD were assessed during endothelium-independent stimulation with intravenous adenosine and during endothelium-dependent stimulation with intracoronary infusion of acetylcholine. Serum values of soluble CD40 ligand (sCD40L), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), and C-reactive protein (CRP) were measured. Impaired MPRI correlated significantly with a decrease in coronary blood flow reserve after both endothelium-dependent (p = 0.033) and endothelium-independent (p = 0.022) stimulation. Serum levels above the median of all normal ranged biomarkers sCD40L, TNF-alpha, IL-6, sICAM-1 and CRP were associated with an impaired MPRI for stimulation with adenosine as well as acetylcholine. In multivariable analyses, sCD40L (p < 0.001) and TNF-alpha (p = 0.011) were significantly associated with a decrease in MPRI on adenosine, as were TNF-alpha (p = 0.016) and sICAM-1 (p = 0.022) for a decrease in MPRI on acetylcholine. MPRI on adenosine significantly correlated with MPRI on acetylcholine (p < 0.001). Therefore, the present study demonstrates safety and feasibility of an intracoronary infusion of acetylcholine during CMR perfusion analysis, thus allowing direct assessment of endothelial dependent vasomotor function at the myocardial level by CMR. Furthermore, we show that an impaired myocardial perfusion reserved in CMR is associated with established biomarkers of early atherosclerosis and significantly correlated with CMD. CMR combined with adenosine could be proposed as a non-invasive tool to evaluate CMD.
J Cardiovasc Magn Reson 2006
PMID:Myocardial perfusion reserve in cardiovascular magnetic resonance: Correlation to coronary microvascular dysfunction. 1706 99

Angiotensin II and glucose share components of their intracellular redox signaling pathways in endothelial and inflammatory cells. We hypothesized that valsartan, an angiotensin II blocker, attenuates hyperglycemia-induced endothelial dysfunction and downregulates release of proinflammatory cytokines from leukocytes. A sustained hyperglycemic clamp (12 mmol/L) to induce endothelial dysfunction was performed in healthy volunteers before and after 4 weeks of treatment with 160 mg of valsartan. Brachial artery flow-mediated vasodilation (FMD), lipopolysaccharide-induced release of interleukin-6 and TNF-alpha from peripheral blood leukocytes ex vivo, and circulating proinflammatory cytokines were determined before and during the clamp. The hyperglycemic clamp induced a decrease in FMD from 9.2 +/- 0.8 (t = 0 hr) to 4.4+/- 0.5 (t = 2 hr), 3.8 +/- 0.5 (t = 4 hr), and 4.8 +/- 0.5% (t = 22 hr) during the clamp. Valsartan attenuated endothelial dysfunction [FMD 7.0 +/- 0.7 (t = 2 hr), 6.1 +/- 0.7 (t = 4 hr), 6.2 +/- 0.6% (t = 22 hr); P < 0.005] and decreased the release of interleukin-6 and TNF-alpha from leukocytes both before and during the clamp (P < 0.05). Valsartan improves hyperglycemia-induced endothelial dysfunction and reduces the cytokine response to an inflammatory stimulus. A pathophysiological link between the effects of hyperglycemia and the renin-angiotensin system on endothelium and peripheral blood leukocytes may underlie the beneficial effects of inhibitors of the renin-angiotensin system on cardiovascular outcome in patients with diabetes mellitus.
J Cardiovasc Pharmacol 2007 Jan
PMID:Angiotensin II type 1 receptor blockade improves hyperglycemia-induced endothelial dysfunction and reduces proinflammatory cytokine release from leukocytes. 1726 57

Antiinflammatory properties of losartan are currently unclear. This study tested the hypothesis that losartan itself has an antiinflammatory effect comparable to that of simvastatin. Human umbilical vein endothelial cells (HUVECs) were (1) incubated with culture medium alone, (2) incubated with added C-reactive protein (CRP) (25, 50, 75, and 100 microg/mL) for stimulation, and (3) pretreated with losartan (stepwise increased dose: 100, 300, 500, and 750 micromol/L) and simvastatin (stepwise increased dose: 25, 50, 75, and 100 micromol/L) for 4 hours before adding CRP for stimulation. Surface expression of vascular cell adhesion molecule-1 (VCAM-1) was determined by flow cytometry. Supernatant levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) were measured by ELISA. Experimental results showed that the effect of CRP on VCAM-1 expression and supernatant levels of MCP-1 and IL-6 increases stepwise as CRP concentrations increase from 25 to 50 to 75 to 100 microg/mL (all P < 0.001). The effect of CRP on VCAM-1 expression in HUVECs and supernatant levels of MCP-1 and IL-6 were significantly suppressed by 25 micromol/L simvastatin with stepwise increased suppression as simvastatin dose increased to 50, 75, and 100 micromol/L (all P < 0.0001). However, losartan did not significantly suppress CRP's effect on VCAM-1 expression in HUVECs (P > 0.5). Moreover, losartan did not suppress CRP's effect on MCP-1 and IL-6 secretion unless a high dose (> or =500 micromol/L) of losartan was used. Compared with simvastatin, losartan had less effect on suppression of CRP-mediated inflammation.
J Cardiovasc Pharmacol 2007 Jan
PMID:Impact of simvastatin and losartan on antiinflammatory effect: in vitro study. 1726 59

Previous studies showed that cardiopulmonary bypass (CPB) was directly associated with a global activation of the inflammatory response, production of oxygen free radicals, and signs of myocardial injury. We therefore evaluated, in the weakest patients, the biological and clinical benefits of a therapeutic optimization of CPB through the combination of several antiinflammatory procedures. High-risk patients undergoing cardiac surgery under CPB were included in this prospective randomized study. Control patients (n = 14) underwent conventional CPB, and treated patients (n = 13) underwent a CPB with Baxter Duraflo II heparin-coated circuits, high doses of aprotinin, and pre-CPB hemofiltration. Usual clinical hemodynamic and biological criteria, inflammation, and oxidative stress markers were measured before, during, and to the second postoperative day. Free radicals were quantified using electronic spin resonance spectroscopy with a spin trap. Significantly lower concentrations of C-reactive protein, interleukin-6, creatine kinase-MB, I-troponin, lactic acid, and systemic free radicals were observed in the plasma of treated patients. These patients had a reduction of postoperative complications and of the length of stay in the intensive care unit. Therefore, pre-CPB therapeutic optimization can reduce the inflammatory response, lower the level of oxidative stress, and help to ameliorate clinical outcome in high-risk patients.
J Cardiovasc Pharmacol 2007 Jan
PMID:In high-risk patients, combination of antiinflammatory procedures during cardiopulmonary bypass can reduce incidences of inflammation and oxidative stress. 1726 62


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