Home About us Contact
|
Home About us Contact | ||
|
|
||
Plaque Instability (plaque + instability)
Selected AbstractsProcoagulant and inflammatory response of virus-infected monocytesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2002J. J. M. Bouwman Abstract Background Monocytes play a prominent role in inflammation, coagulation and atherosclerosis by their ability to produce tissue factor (TF) and cytokines. The aim of the present study was to establish whether virus-infected monocytes initiate coagulation. In addition, the production of cytokines by monocytes may accelerate the chronic process of atherosclerosis and may contribute to coronary syndromes by eliciting plaque instability. Materials and methods Monocytes were isolated by Vacutainer®, BD Biosciences, Alphen aan den Rijn, Netherlands and subsequent magnetic cell sorting (MACS®, Milteny Biotec, Bergish Gladbach, Germany). Coagulation times in normal pooled plasma and Factor VII-deficient plasma were measured after infection with cytomegalovirus (CMV), Chlamydia pneumoniae (Cp) and influenza A\H1N1. Anti-TF antibodies were added to neutralize TF expressed on monocytes. Interleukins (IL) 6, 8 and 10 were measured in the supernatants. Results Chlamydia pneumoniae- and CMV-infected monocytes decreased the clotting time by 60%, and influenza-infected monocytes by 19%, as compared to uninfected monocytes. Procoagulant activity was absent when Factor VII-deficient plasma or anti-TF antibodies were used. Monocytes produced both IL-6 and IL-8 after infection with CMV (317 pg mL,1 and 250 pg mL,1) or Cp (733 pg mL,1 and 268 pg mL,1). Similar results were obtained for influenza virus-infected monocytes, but the levels of both cytokines were 3,5-fold higher (1797 pg mL,1 and 725 pg mL,1). Interleukin-10 was not produced by infected monocytes. Conclusion The procoagulant activity of virus-infected monocytes is TF-dependent. Although influenza infection did not generate a significant reduction in clotting time, the pronounced expression of IL-6 and IL-8 may induce local and/or systemic inflammatory reactions, which may be associated with plaque rupture and atherosclerosis. The lack of production of the anti-inflammatory cytokine IL-10 may even accelerate these processes. [source] Variation in the human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) gene is associated with plasma soluble LOX-1 levelsEXPERIMENTAL PHYSIOLOGY, Issue 9 2008Tina E. Brinkley The lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) expressed on vascular cells plays a major role in atherogenesis by internalizing and degrading oxidized low-density lipoprotein. LOX-1 can be cleaved from the cell surface and released as soluble LOX-1 (sLOX-1), and elevated sLOX-1 levels may be indicative of atherosclerotic plaque instability. We examined associations between the LOX-1 gene 3,UTR-C/T and G501C polymorphisms and plasma sLOX-1 levels in 97 healthy older men and women. The frequencies for the 3,UTR-T and 501C alleles were 46 and 10%, respectively. Plasma sLOX-1 levels were significantly higher in the 3,UTR CC genotype group compared with both the CT (P= 0.02) and TT genotype groups (P= 0.002). Plasma sLOX-1 levels were also significantly higher in the 501GC genotype group compared with the GG genotype group (P= 0.004). In univariate analyses, sLOX-1 levels were significantly associated with both the 3,UTR-C/T and G501C polymorphisms. These associations remained significant after adjusting for age, sex, race and body mass index. In conclusion, variation in the LOX-1 gene is associated with plasma sLOX-1 levels in older men and women. [source] Human plasminogen kringle 1,5 reduces atherosclerosis and neointima formation in mice by suppressing the inflammatory signaling pathwayJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2010P. C. CHANG Summary.,Background:,Activation of vascular endothelial cells plays an important role in atherogenesis and plaque instability. Recent research has demonstrated that late-stage inhibition of plaque angiogenesis by angiostatin (kringle 1,4) reduces macrophage accumulation and slows the progression of advanced atherosclerosis. Kringle 1,5 (K1,5) is a variant of angiostatin that contains the first five kringle domains of plasminogen. Objective: To investigate whether K1,5 has an inhibitory effect on early-stage atherosclerosis, using the apolipoprotein E (ApoE)-deficient mouse model and a carotid artery ligation model. Methods: ApoE-deficient mice received K1,5 treatment for 4 weeks, and the severity of aortic atherosclerosis was measured. In the ligation model, the left common carotid arteries of C57BL/6 mice were ligated near the carotid bifurcation, and the mice received K1,5 for 4 weeks. Human umbilical vein endothelial cells were pretreated with K1,5 before tumor necrosis factor-, (TNF-,) treatment to explore the anti-inflammatory effect of K1,5. Results: The areas of the lesion in the aortas of ApoE-deficient mice that received K1,5 treatment were notably decreased, and the formation of carotid neointima in the C57BL/6 mice was decreased by treatment with K1,5. Expression of TNF-,-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 was inhibited by K1,5 treatment, possibly via downregulation of translocation of nuclear factor-,B and expression of reactive oxygen species. Conclusions: K1,5 reduced atherosclerosis and neointima formation in mice, possibly through inhibition of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in endothelial cells. [source] Chronic arthritis aggravates vascular lesions in rabbits with atherosclerosis: A novel model of atherosclerosis associated with chronic inflammationARTHRITIS & RHEUMATISM, Issue 9 2008Raquel Largo Objective To determine whether systemic inflammation induced by chronic antigen-induced arthritis (AIA) accelerates vascular lesions in rabbits with atherosclerosis. Methods Two models of atherosclerosis and chronic AIA were combined. Atherosclerosis was induced by coupling a hyperlipemic diet with an endothelial lesion at the femoral arteries, while chronic AIA was induced by ovalbumin injection. Markers in sera and peripheral blood mononuclear cells (PBMCs) as well as vessels and synovial membranes from the rabbits with the double phenotype (both chronic AIA and atherosclerosis) were compared with those from rabbits with each disease alone. Results Serum levels of interleukin-6, C-reactive protein, and prostaglandin E2 increased in rabbits with both chronic AIA and atherosclerosis as compared with healthy animals or animals with either chronic AIA alone or atherosclerosis alone. NF-,B binding and CCL2 and cyclooxygenase 2 (COX-2) expression were higher in PBMCs from rabbits with both chronic AIA and atherosclerosis than in PBMCs from healthy rabbits. The intima-media thickness ratio of femoral arteries was equally increased in rabbits with atherosclerosis alone and in rabbits with both chronic AIA and atherosclerosis, but the latter group showed a higher level of macrophage infiltration. Femoral CCL2 and COX-2 expression was increased in rabbits with both chronic AIA and atherosclerosis as compared with rabbits with atherosclerosis alone. In the aortas, vascular lesions were found in 27% of rabbits with atherosclerosis alone and in 60% of rabbits with both chronic AIA and atherosclerosis. Rabbits with both chronic AIA and atherosclerosis exhibited more severe synovitis and higher synovial expression of CCL2 than did rabbits with chronic AIA alone. Conclusion The onset of chronic AIA in animals with atherosclerosis resulted in the local and systemic up-regulation of mediators of tissue inflammation and plaque instability associated with a higher incidence of aortic lesions. This model could represent a novel approach to the study of inflammation-associated atherosclerosis. [source] Vascular endothelial growth factor is associated with histological instability of carotid plaques,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2008D. A. Russell Background: Vascular endothelial growth factor (VEGF) promotes events favouring carotid plaque instability: inflammatory chemoattraction, thrombogenesis, and upregulation of matrix metalloproteinases and cell adhesion molecules. The aim of this study was to assess neovascularization, VEGF and its receptors in high-grade stable and unstable carotid plaques. Methods: Immunohistochemical staining for CD34, VEGF, VEGF receptor (VEGFR) 1 and VEGFR2 was performed in 34 intact carotid endarterectomy specimens, and compared in sections demonstrating maximal histological instability (cap rupture/thinning) or, if stable, maximal stenosis. Results: VEGF staining was increased in 12 unstable compared with 22 stable plaques (median (interquartile range, i.q.r.) plaque score 4·0 (4·0,4·0) versus 3·0 (2·0,3·0); P = 0·002) with upregulation of VEGFR1 (plaque score 4·0 (2·0,4·0) versus 2·0 (1·0,3·0); P = 0·016). In unstable plaques this was associated with increased microvessel density in the cap (median (i.q.r.) 12·1 (4·0,30·0) versus 1·1 (0·0,7·3) microvessels/mm2; P = 0·017) and shoulder regions (7·7 (3·4,21·4) versus 3·1 (0·4,10·8) microvessels/mm2; P = 0·176). Conclusion: Increased VEGF and receptor staining were seen in histologically unstable carotid plaques. Although these differences could reflect cytokine-driven inflammatory events accompanying plaque instability, VEGF and VEGFR1 could be key mediators. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Association between plaque instability, angiogenesis and symptomatic carotid occlusive disease,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2001R. Mofidi Background: Angiogenesis is a recognized feature of the atherosclerotic process and has been described in the context of unstable coronary atherosclerotic lesions. The aim of this study was to assess the association between angiogenesis in atherosclerotic carotid plaques and microscopic features of plaque instability, in particular intraplaque haemorrhage. Methods: Consecutive patients undergoing carotid endarterectomy were included. Endarterectomy specimens were divided into their constituent atherosclerotic lesions. Histological sections were prepared and stained with haematoxylin and eosin, and immunohistochemically with an endothelial cell marker (CD34). The quantity of intraplaque haemorrhage was measured in transverse histological sections using computerized image analysis. Microvessel counts were performed in CD34-stained sections and were verified through computerized image analysis. Results: Some 239 atherosclerotic lesions from 73 patients were available for analysis; 73 were early lesions, 74 were raised fibroatheromas and 92 were unstable atherosclerotic plaques. One hundred and fifty lesions were not haemorrhagic; 89 exhibited intraplaque haemorrhage, of which 28 involved less than 50 per cent of the plaque sectional area. There were higher microvessel counts in plaques containing over 50 per cent haemorrhage (P < 0·0001), unstable atherosclerotic lesions (P < 0·0001) and atherosclerotic lesions obtained from symptomatic patients (P < 0·001). Conclusion: There are strong associations between plaque vascularity, quantity of intraplaque haemorrhage and presence of symptomatic carotid occlusive disease. © 2001 British Journal of Surgery Society Ltd [source] 2,3,4,,5-TETRAHYDROXYSTILBENE-2- O -,- d -GLUCOSIDE SUPPRESSES MATRIX METALLOPROTEINASE EXPRESSION AND INFLAMMATION IN ATHEROSCLEROTIC RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2008Wei Zhang SUMMARY 1In coronary artery disease, the typical atheromatous plaque consists of a lipid core containing various inflammatory cells and a fibrous cap composed mostly of extracellular matrix. Both matrix metalloproteinases (MMPs) and inflammation are involved in the initiation of atherosclerotic plaques and plaque instability. 22,3,4¢,5-Tetrahydroxystilbene-2- O -b- d -glucoside (TSG) reduces the blood lipid content and prevents the atherosclerotic process, but the mechanism of action of TSG is unclear. The purpose of the present study was to test whether TSG can suppress MMP activation and inflammation in atherosclerotic rats. 3Sixty male Sprague-Dawley rats were randomly divided into six groups. Atherosclerosis was induced by feeding rats a hyperlipidaemic diet; TSG (120, 60 or 30 mg/kg per day) was administered by oral gavage. After 12 weeks of treatment, rats were killed (ethyl carbamate 1200 mg/kg) and serum lipids, C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-a were measured. Haematoxylin,eosin (H&E) staining was used to examine histopathological changes in the aorta. The mRNA and protein expression of MMPs were assayed by reverse transcription,polymerase chain reaction, immunohistochemistry and western blotting. Simvastatin (2 mg/kg per day) was administered as a positive control, whereas the vehicle (0.9% NaCl) group served as the untreated control. 4In the present study, TSG significantly and dose-dependently attenuated the hyperlipidaemic diet-induced alterations in serum lipid profile and increases in CRP, IL-6 and TNF-a levels. In addition, TSG normalized the structure of the aortic wall and suppressed the expression of MMP-2 and MMP-9 at both the mRNA and protein level in the rat aortic wall. 5In summary, TSG suppresses the expression of MMP-2 and MMP-9 and inhibits inflammation in the diet-induced atherosclerotic rats. [source] | ||||||||||