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Vascular Inflammation (vascular + inflammation)
Selected AbstractsMarkers of eosinophilic inflammation and risk prediction in patients with coronary artery diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2006C. Falcone Abstract Background, The eotaxin family comprises three distinct peptides (eotaxin, eotaxin-2 and eotaxin-3) which have been implicated in eosinophilic inflammation. In vitro and clinical studies suggest that eotaxins could play a role in vascular inflammation, but no data are available on their prognostic significance in patients with angiographically documented coronary artery disease (CAD). Materials and methods, Baseline plasma samples were obtained from 1014 patients with documented CAD. We tested the predictive effect of markers of eosinophilic inflammation and C-reactive protein (CRP) on death from cardiovascular causes and nonfatal myocardial infarction over a 2·7,4·1-year follow-up period. Results, Unexpectedly, lower eotaxin-3 concentrations were observed in patients with adverse cardiovascular events, whereas both eotaxin and eotaxin-2 showed no association with risk. After adjustment for most potential confounders, patients in the upper-quartile of eotaxin-3 levels had a 0·42 hazard-ratio (95% CI, 0·29,0·61, P < 0·001) for adverse events compared with subjects in the lower-quartile. The highest risk of future cardiovascular events was observed in subjects with combined elevation of CRP and reduction of eotaxin-3; 4·4 hazard-ratio (95% CI, 2·1,9·5, P < 0·001). Importantly, receiver-operating-characteristic curves analysis suggested a superior prognostic value of eotaxin-3 compared with CRP for predicting cardiac events in patients with CAD. Conclusions, Low levels of eotaxin-3 are an independent predictor of future adverse cardiovascular events in patients with CAD and may be useful for risk stratification. [source] Thiazolidinedione derivatives in diabetes and cardiovascular disease: an updateFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2008Pantelis A. Sarafidis Abstract As the incidence and the public health impact of type 2 diabetes are constantly rising, treatment of hyperglycemia, prevention of diabetes-related complications are currently top medical priorities. Within the last decade several new classes of oral hypoglycemic agents were added to our armamentarium against diabetes. Among these new classes, the group of thiazolidinediones, which act through reduction of insulin resistance is perhaps the most widely used. For about 20 years, numerous background and clinical studies have evaluated the beneficial and adverse effects of these compounds. Current knowledge suggests that thiazolidinediones are as effective as metformin or sulfonylurea derivatives in improving glycemic control and exert several other beneficial metabolic and vascular effects, such as improvement in lipid profile, blood pressure lowering, redistribution of body fat away from the central compartment, microalbuminuria regression, reduction in subclinical vascular inflammation and others. On the other hand, currently used thiazolidinediones have well-established side effects, most important of which are fluid retention leading to weight gain and heart failure deterioration. Further, in the expectance of proper outcome studies to clarify the effects of these agents in cardiovascular morbidity and mortality, data from recent meta-analyses suggest that rosiglitazone may increase the risk for some cardiovascular outcomes. This article will discuss all the above issues attempting to provide an updated overview of this expanding field. [source] Metabolic syndrome and mitochondrial function: Molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Garth L. Nicolson Abstract Metabolic syndrome consists of a cluster of metabolic conditions, such as hypertriglyeridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that,in combination with genetic susceptibility and abdominal obesity,are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart disease. One of the defects in metabolic syndrome and its associated diseases is excess cellular oxidative stress (mediated by reactive oxygen and nitrogen species, ROS/RNS) and oxidative damage to mitochondrial components, resulting in reduced efficiency of the electron transport chain. Recent evidence indicates that reduced mitochondrial function caused by ROS/RNS membrane oxidation is related to fatigue, a common complaint of MS patients. Lipid replacement therapy (LRT) administered as a nutritional supplement with antioxidants can prevent excess oxidative membrane damage, restore mitochondrial and other cellular membrane functions and reduce fatigue. Recent clinical trials have shown the benefit of LRT plus antioxidants in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Thus LRT plus antioxidant supplements should be considered for metabolic syndrome patients who suffer to various degrees from fatigue. J. Cell. Biochem. 100: 1352,1369, 2007. © 2007 Wiley-Liss, Inc. [source] Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammationAGING CELL, Issue 3 2009Leocadio Rodríguez-Mańas Summary Vascular endothelial dysfunction occurs during the human aging process, and it is considered as a crucial event in the development of many vasculopathies. We investigated the underlying mechanisms of this process, particularly those related with oxidative stress and inflammation, in the vasculature of subjects aged 18,91 years without cardiovascular disease or risk factors. In isolated mesenteric microvessels from these subjects, an age-dependent impairment of the endothelium-dependent relaxations to bradykinin was observed. Similar results were observed by plethysmography in the forearm blood flow in response to acetylcholine. In microvessels from subjects aged less than 60 years, most of the bradykinin-induced relaxation was due to nitric oxide release while the rest was sensitive to cyclooxygenase (COX) blockade. In microvessels from subjects older than 60 years, this COX-derived vasodilatation was lost but a COX-derived vasoconstriction occurred. Evidence for age-related vascular oxidant and inflammatory environment was observed, which could be related to the development of endothelial dysfunction. Indeed, aged microvessels showed superoxide anions (O2,) and peroxynitrite (ONOO,) formation, enhancement of NADPH oxidase and inducible NO synthase expression. Pharmacological interference of COX, thromboxane A2/prostaglandin H2 receptor, O2,, ONOO,, inducible NO synthase, and NADPH oxidase improved the age-related endothelial dysfunction. In situ vascular nuclear factor-,B activation was enhanced with age, which correlated with endothelial dysfunction. We conclude that the age-dependent endothelial dysfunction in human vessels is due to the combined effect of oxidative stress and vascular wall inflammation. [source] Enhanced monocyte migration and pro-inflammatory cytokine production by Porphyromonas gingivalis infectionJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2010A. Pollreisz Pollreisz A, Huang Y, Roth GA, Cheng B, Kebschull M, Papapanou PN, Schmidt AM, Lalla E. Enhanced monocyte migration and pro-inflammatory cytokine production by Porphyromonas gingivalis infection. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01225.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective:,Porphyromonas gingivalis, a major periodontal pathogen, has been reported to be involved in atherogenesis. In order to further understand this pathogen's link with systemic inflammation and vascular disease, we investigated its influence on murine monocytes and macrophages from three different sources. Material and Methods:, Concanavalin A-elicited peritoneal macrophages, peripheral blood monocyte-derived macrophages and WEHI 274.1 monocytes were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. Results:, Infection with P. gingivalis 381 markedly induced monocyte migration and significantly enhanced production of the pro-inflammatory cytokines, tumor necrosis factor-, and interleukin-6. Consistent with a role for this pathogen's major fimbriae and/or its invasive capacity, infection with DPG3 had a minimal effect on both monocyte attraction and pro-inflammatory cytokine production. Conclusion:, Since monocyte recruitment and activation are important steps in the development of vascular inflammation and atherosclerosis, these results suggest that P. gingivalis infection may be involved in these processes. [source] Postinjury vascular intimal hyperplasia in mice is completely inhibited by CD34+ bone marrow-derived progenitor cells expressing membrane-tethered anticoagulant fusion proteinsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2006D. CHEN Summary.,Background:,Coagulation proteins promote neointimal hyperplasia and vascular remodelling after vessel injury, but the precise mechanisms by which they act in vivo remain undetermined. Objectives:,This study, using an injury model in which the neointima is derived from bone marrow (BM)-derived cells, compared inhibition of tissue factor or thrombin on either BM-derived or existing vascular smooth muscle cells. Methods:,Two transgenic (Tg) mouse strains expressing membrane-tethered tissue factor pathway inhibitor (TFPI) or hirudin (Hir) fusion proteins driven by an , smooth muscle actin (SMA) promoter were generated (, -TFPI-Tg and , -Hir-Tg) and the phenotype after wire-induced endovascular injury was compared with that in wild-type (WT) controls. Results:,WT mice developed progressive neointimal expansion, whereas injury in either Tg was followed by repair back to a preinjured state. This was also seen when WT mice were reconstituted with BM from Tg mice but not when Tgs were reconstituted with WT BM, in which injury was followed by slowly progressive neointimal expansion. Injection of CD34+ cells from Tg mice into injured WT mice resulted in the accumulation of fusion protein-expressing cells from day 3 onwards and an absence of neointimal hyperplasia in those areas. Conclusions:,Neointimal development after wire-induced endovascular injury in mice was completely inhibited when BM-derived cells infiltrating the damaged artery expressed membrane tethered anticoagulant fusion proteins under an , -SMA promoter. These findings enhance our understanding of the pathological role that coagulation proteins play in vascular inflammation. [source] Meta-Analyses Qualify Metzincins and Related Genes as Acute Rejection Markers in Renal Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010S. Rödder Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T-cell,mediated AR are tubulointerstitial and vascular inflammation associated with excessive extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t- and i-scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, -9, TIMP1, -2, thrombospondin2 (THBS2) and fibrillin1. RT-PCR using microdissected glomeruli/tubuli confirmed MMP7, -9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, -9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/-9 represent potential molecular AR markers. [source] The contact/kinin and complement systems in vasculitisAPMIS, Issue 2009DIANA KARPMAN Vasculitides are a group of conditions with marked inflammation in and around vessel walls and vascular leakage. These conditions may involve the presence of auto-antibodies such as ANCA or may be mediated by other autoimmune or pathogenic mechanisms. Regardless of the primary trigger, vasculitides entail activation of the complement system as well as the contact/kinin system. In vivo and in vitro data support the involvement of these systems showing activation of the alternative, classical and lectin complement pathways as well as release of bradykinin at sites of vascular inflammation. This short review will summarize some of the data regarding the participation of these systems and the interplay between the complement and kinin systems as well as their interaction with the endothelium and neutrophils. Although these systems do not play a primary role in induction of vasculitis, the peptides released contribute to inflammation and vascular leakage and may thus be identified as potential therapeutic targets. [source] Th17 and natural Treg cell population dynamics in systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 5 2009Ji Yang Objective To investigate the relative abundance and activities of Th17 cells and natural Treg cells in systemic lupus erythematosus (SLE). Methods Blood samples were collected from 50 adult patients with SLE. Samples were processed to detect Th17 cells and natural Treg cells by flow cytometry, and related gene expression was assessed by real-time reverse transcription,polymerase chain reaction. Skin biopsy specimens were collected for histologic assessment. The function of Th17 cells in relation to human umbilical vein endothelial cells (HUVECs) was studied in vitro. Th17 cells were also examined in lupus-prone MRL/Mp- lpr/lpr (MRL/lpr) mice. Results We demonstrated the presence of Th17 cells among the peripheral blood mononuclear cells (PBMCs) and in the involved organs of patients with active SLE. Both the percentage of circulating Th17 cells and the ability to produce interleukin-17A (IL-17A) were increased in samples derived from patients with active SLE. The number of Th17 cells increased during SLE flare, especially in patients with vasculitis, and decreased following certain treatments. We observed that IL-17A from patients with SLE could induce adhesion molecule messenger RNA expression in HUVECs and adhesion of T cells to HUVECs. An increase in the percentage of Th17 cells was correlated with natural Treg cell depletion during disease flare. Finally, expansion of the Th17 cell population was detected in MRL/lpr mice. Conclusion SLE flare might be linked to the expansion of the Th17 cell population and the depletion of natural Treg cell subpopulations. Expansion of the Th17 cell population might be related to a distinct cytokine environment in active SLE. Th17 cells and microenvironmental IL-17A are involved in vascular inflammation in SLE. Antagonism of Th17 cells by IL-17A,blocking antibodies should be explored as a treatment of SLE. [source] Inflammatory rheumatic disease and smoking are predictors of aortic inflammation: A controlled study of biopsy specimens obtained at coronary artery surgery,ARTHRITIS & RHEUMATISM, Issue 6 2007Ivana Hollan Objective Several inflammatory rheumatic diseases are associated with accelerated atherosclerosis. Atherosclerosis may result from systemic and/or local vascular inflammation. The aim of this study was to evaluate the occurrence of chronic inflammatory infiltrates in the aortas of patients with and those without inflammatory rheumatic disease who had undergone coronary artery bypass graft (CABG) surgery, and to assess the relationship between the infiltrates and other factors thought to play a role in atherosclerosis, such as smoking. Methods Aortic specimens routinely removed during CABG surgery in 66 consecutive patients with inflammatory rheumatic disease and 51 control patients without inflammatory rheumatic disease were examined by light microscopy for the occurrence, location, and severity of chronic inflammatory infiltrates and atherosclerotic lesions. Results Mononuclear cell infiltrates in the inner adventitia (apart from those localized along the epicardium) were more frequent in the group of patients with inflammatory rheumatic disease (47% versus 20%; P = 0.002, odds ratio [OR] OR 3.6, 95% confidence interval [95% CI] 1.6,8.5), and the extent of these infiltrates was greater. Multivariate analyses revealed that the occurrence of mononuclear cell infiltrates was associated with inflammatory rheumatic disease (OR 2.99, P = 0.020) and current smoking (OR 3.93, P = 0.012), and they were observed in 6 of 7 patients with a history of aortic aneurysm. Inflammatory infiltrates in the media were seen only in patients with inflammatory rheumatic disease. The frequency of atherosclerotic lesions, inflammation within the plaques, and epicardial inflammatory infiltrates in the 2 groups was equal. Conclusion Among aortic samples collected during CABG surgery, those obtained from patients with inflammatory rheumatic disease had more pronounced chronic inflammatory infiltration in the media and inner adventitia than those obtained from control patients. Current smoking was an independent predictor of chronic inner adventitial infiltrates. The infiltrates may represent an inflammatory process that promotes atherosclerosis and formation of aneurysms. [source] Takayasu arteritis: Utility and limitations of magnetic resonance imaging in diagnosis and treatmentARTHRITIS & RHEUMATISM, Issue 6 2002Elisa Tso Objective Previous studies have confirmed the poor correlation of symptoms, signs, and levels of acute-phase reactants with disease activity in ,50% of all patients with Takayasu arteritis (TA). Invasive angiographic studies demonstrate vessel lumen anatomy, but do not provide qualitative information about the vessel wall. Moreover, sequential invasive angiographic studies expose patients to high-dose ionizing radiation and catheter/procedure-related morbidity. The aim of the present study was to determine the utility of new developments in vascular magnetic resonance (MR) technology in patients with TA. Methods Electrocardiogram-gated "edema-weighted" MR was used to evaluate the aorta and its primary branches with regard to the vascular lumen, vessel wall anatomy, and vessel wall edema in 24 TA patients (77 studies). Inclusion criteria were age <50 years and features of TA on both clinical examination and invasive angiographic studies. Patients were stratified based on clinical and laboratory indications of having either unequivocally active disease, inactive disease, or uncertain disease status. Results MR revealed vessel wall edema in 94% (17 of 18), 81% (13 of 16), and 56% (24 of 43) of studies obtained during periods of unequivocally active disease, uncertain disease activity, and apparent clinical remission, respectively. Westergren erythrocyte sedimentation rate and C-reactive protein values did not correlate with either the clinical assessment of disease activity or MR evidence of vascular edema. The frequency of presumed vascular inflammation (edema), as assessed by MR, in patients who appeared to be in remission was similar to the reported frequency of new angiographic lesions and histopathologic evidence of active disease in surgical specimens from patients thought to be in remission. However, the presence of edema within vessel walls did not consistently correlate with the occurrence of new anatomic changes found on subsequent studies. Conclusion Inconsistencies in the presence or absence of vessel edema and subsequent anatomic changes have cast doubt on the utility of edema-weighted MR imaging as a sole guide to disease activity and treatment in TA. In this study, the greatest utility of MR was in providing a safe, noninvasive means of assessing changes in vascular anatomy. [source] Homocysteine is positively associated with cytokine IL-18 plasma levels in coronary artery bypass surgery patientsBIOFACTORS, Issue 2 2005Craig Steven Mclachlan Abstract Homocysteine, cytokines (IL-18, IL-6, IL-8) are involved in vascular inflammation and coronary artery disease. Homocysteine influences endothelial IL-6 and IL-8 cytokine expression and release, however, an association between homocysteine and IL-18 has not been previously investigated in endothelial/smooth muscle cells and or in coronary artery disease. We report in 9 coronary artery bypass surgery (CABG) patients a positive correlation r=0.86 between homocysteine and IL-18 plasma levels (p<0.05). Plasma IL-18 levels are significantly higher in those patients with elevated homocysteine compared to those with normal levels (p<0.02; 153 ± 19 pg/ml versus 116 ± 14 pg/ml respectively). Our in vitro cell culture studies suggest that the source of IL-18 in CABG patients with elevated homocysteine is not from vascular smooth muscle or endothelial cells. [source] Chitosan Oligosaccharides Inhibit the Expression of Interleukin-6 in Lipopolysaccharide-induced Human Umbilical Vein Endothelial Cells Through p38 and ERK1/2 Protein KinasesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2010Hong-Tao Liu However, the potential roles of COS in the treatment of vascular inflammations remain unknown. In the present study, we examined the effects of COS on interleukin-6 (IL-6) production in human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS). Induction of HUVECs with LPS (100 ng/ml) increased the mRNA expression and protein secretion of IL-6 (versus the vehicle-treated group, p < 0.01), which were significantly reverted by the pre-treatment with COS (50,200 ,g/ml) for 24 hr before LPS exposure (versus the LPS-treated group, p < 0.05 or 0.01). Signal transduction studies showed that the pre-treatment of HUVECs with COS (50,200 ,g/ml) for 24 hr markedly inhibited the LPS-induced over-expression of phosphorylated p38 mitogen-activated protein kinase (MAPK), phosphorylated ERK1/2 and nuclear factor ,B (NF-,B). Moreover, the LPS-induced NF-,B activation was suppressed by the specific ERK1/2 inhibitor PD98059 (30 ,M) (versus the LPS-treated group, p < 0.01), but not by the specific p38 MAPK inhibitor SB203580 (25 ,M). Additionally, both MAPK inhibitors markedly suppressed LPS-induced IL-6 mRNA expression in HUVECs (versus the LPS-treated group, p < 0.01). In conclusion, our results suggest that COS inhibit LPS-induced up-regulation of IL-6 in HUVECs, and this can be regulated by at least two parallel signalling pathways: one via p38 MAPK pathway independent of NF-,B activation and one via ERK1/2 pathway dependent on NF-,B activation. [source] | |||||||||||||