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Sample records for atherosclerotic lesion formation

  1. Dietary carnosine prevents early atherosclerotic lesion formation in apolipoprotein E-null mice.

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    Barski, Oleg A; Xie, Zhengzhi; Baba, Shahid P; Sithu, Srinivas D; Agarwal, Abhinav; Cai, Jian; Bhatnagar, Aruni; Srivastava, Sanjay

    2013-06-01

    Atherosclerotic lesions are associated with the accumulation of reactive aldehydes derived from oxidized lipids. Although inhibition of aldehyde metabolism has been shown to exacerbate atherosclerosis and enhance the accumulation of aldehyde-modified proteins in atherosclerotic plaques, no therapeutic interventions have been devised to prevent aldehyde accumulation in atherosclerotic lesions. We examined the efficacy of carnosine, a naturally occurring β-alanyl-histidine dipeptide, in preventing aldehyde toxicity and atherogenesis in apolipoprotein E-null mice. In vitro, carnosine reacted rapidly with lipid peroxidation-derived unsaturated aldehydes. Gas chromatography mass-spectrometry analysis showed that carnosine inhibits the formation of free aldehydes 4-hydroxynonenal and malonaldialdehyde in Cu(2+)-oxidized low-density lipoprotein. Preloading bone marrow-derived macrophages with cell-permeable carnosine analogs reduced 4-hydroxynonenal-induced apoptosis. Oral supplementation with octyl-D-carnosine decreased atherosclerotic lesion formation in aortic valves of apolipoprotein E-null mice and attenuated the accumulation of protein-acrolein, protein-4-hydroxyhexenal, and protein-4-hydroxynonenal adducts in atherosclerotic lesions, whereas urinary excretion of aldehydes as carnosine conjugates was increased. The results of this study suggest that carnosine inhibits atherogenesis by facilitating aldehyde removal from atherosclerotic lesions. Endogenous levels of carnosine may be important determinants of atherosclerotic lesion formation, and treatment with carnosine or related peptides could be a useful therapy for the prevention or the treatment of atherosclerosis.

  2. Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice.

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    Srivastava, Sanjay; Vladykovskaya, Elena N; Haberzettl, Petra; Sithu, Srinivas D; D'Souza, Stanley E; States, J Christopher

    2009-11-15

    Exposure to arsenic-contaminated water has been shown to be associated with cardiovascular disease, especially atherosclerosis. We examined the effect of arsenic exposure on atherosclerotic lesion formation, lesion composition and nature in ApoE-/- mice. Early post-natal exposure (3-week-old mice exposed to 49 ppm arsenic as NaAsO(2) in drinking water for 7 weeks) increased the atherosclerotic lesion formation by 3- to 5-fold in the aortic valve and the aortic arch, without affecting plasma cholesterol. Exposure to arsenic for 13 weeks (3-week-old mice exposed to 1, 4.9 and 49 ppm arsenic as NaAsO(2) in drinking water) increased the lesion formation and macrophage accumulation in a dose-dependent manner. Temporal studies showed that continuous arsenic exposure significantly exacerbated the lesion formation throughout the aortic tree at 16 and 36 weeks of age. Withdrawal of arsenic for 12 weeks after an initial exposure for 21 weeks (to 3-week-old mice) significantly decreased lesion formation as compared with mice continuously exposed to arsenic. Similarly, adult exposure to 49 ppm arsenic for 24 weeks, starting at 12 weeks of age increased lesion formation by 2- to 3.6-fold in the aortic valve, the aortic arch and the abdominal aorta. Lesions of arsenic-exposed mice displayed a 1.8-fold increase in macrophage accumulation whereas smooth muscle cell and T-lymphocyte contents were not changed. Expression of pro-inflammatory chemokine MCP-1 and cytokine IL-6 and markers of oxidative stress, protein-HNE and protein-MDA adducts were markedly increased in lesions of arsenic-exposed mice. Plasma concentrations of MCP-1, IL-6 and MDA were also significantly elevated in arsenic-exposed mice. These data suggest that arsenic exposure increases oxidative stress, inflammation and atherosclerotic lesion formation.

  3. Flaxseed reverses atherosclerotic lesion formation and lowers lipoprotein(a) in ovarian hormone deficiency.

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    Campbell, Sara C; Bakhshalian, Neema; Sadaat, Raz L; Lerner, Megan R; Lightfoot, Stanley A; Brackett, Daniel; Arjmandi, Bahram H

    2013-11-01

    The incidence of cardiovascular disease dramatically increases during menopause, and postmenopausal women seek natural alternatives to hormone therapy. Flaxseed can slow the progression of atherosclerotic lesion formation; however, it is not known whether it can reverse formation that has already occurred. Seventy-two female Golden Syrian hamsters were randomly divided into six groups (n = 12), sham-operated (sham) or ovariectomized (ovx), and kept on the same diet for 120 days to allow for atherosclerotic lesion development. After this 120-day period, whole flaxseed was introduced to the diets of hamsters in three of the groups: group 1 (sham + casein); group 2 (ovx + casein); group 3 (ovx + 7.5% flaxseed); group 4 (ovx + 15% flaxseed); group 5 (ovx + 22.5% flaxseed); and group 6 (ovx + 17β-estradiol). This diet was maintained for an additional 120 days. Lesion regression was examined histologically, and serum was analyzed for total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, Apo A, Apo B, and lipoprotein(a). Results showed that 15% and 22.5% flaxseed, compared with ovx animals, significantly reduced lipoprotein(a) (4.4 mg/dL [ovx] vs 2.15 mg/dL [15% flaxseed] and 0.3 mg/dL [22.5% flaxseed]; P < 0.05) and Apo B (2.8 mg/dL [ovx] vs 2.4 mg/dL [15% flaxseed] and 2.5 mg/dL [22.5% flaxseed]). Flax reduced by 67% the number of animals with aortic arch lesions. All three doses of flax reduce the severity of lesion formation compared with ovx controls. These results support the efficacy of flaxseed in reducing cardiovascular disease risk.

  4. Network analysis reveals a causal role of mitochondrial gene activity in atherosclerotic lesion formation.

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    Vilne, Baiba; Skogsberg, Josefin; Foroughi Asl, Hassan; Talukdar, Husain Ahammad; Kessler, Thorsten; Björkegren, Johan L M; Schunkert, Heribert

    2017-12-01

    Mitochondrial damage and augmented production of reactive oxygen species (ROS) may represent an intermediate step by which hypercholesterolemia exacerbates atherosclerotic lesion formation. To test this hypothesis, in mice with severe but genetically reversible hypercholesterolemia (i.e. the so called Reversa mouse model), we performed time-resolved analyses of mitochondrial transcriptome in the aortic arch employing a systems-level network approach. During hypercholesterolemia, we observed a massive down-regulation (>28%) of mitochondrial genes, specifically at the time of rapid atherosclerotic lesion expansion and foam cell formation, i.e. between 30 and 40 weeks of age. Both phenomena - down-regulation of mitochondrial genes and lesion expansion - were largely reversible by genetically lowering plasma cholesterol (by >80%, from 427 to 54 ± 31 mg/L) at 30 weeks. Co-expression network analysis revealed that both mitochondrial signature genes were highly connected in two modules, negatively correlating with lesion size and supported as causal for coronary artery disease (CAD) in humans, as expression-associated single nucleotide polymorphisms (eSNPs) representing their genes overlapped markedly with established disease risk loci. Within these modules, we identified the transcription factor estrogen related receptor (ERR)-α and its co-factors PGC1-α and -β, i.e. two members of the peroxisome proliferator-activated receptor γ co-activator 1 family of transcription regulators, as key regulatory genes. Together, these factors are known as major orchestrators of mitochondrial biogenesis and antioxidant responses. Using a network approach, we demonstrate how hypercholesterolemia could hamper mitochondrial activity during atherosclerosis progression and pinpoint potential therapeutic targets to counteract these processes. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Biology of atherosclerotic plaque formation: possible role of growth factors in lesion development and the potential impact of soy.

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    Raines, E W; Ross, R

    1995-03-01

    The advanced lesions of atherosclerosis occlude the affected artery by increasing the thickness of the intima. The focal thickening of the intima is due to a large increase in smooth muscle cells, formation of new connective tissue matrix by these smooth muscle cells and, in hyperlipidemic individuals, the accumulation of intracellular and extracellular lipid. Additionally, monocytes and T lymphocytes infiltrate the artery wall. Various forms of "injury" may lead to cellular infiltration and proliferation. Localized cellular infiltration of monocytes and T cells may be due to changes in adhesive properties of the endothelial surface, involving the expression of specific adhesion molecules. The directed cell migration and proliferation may represent the cells' response to polypeptide growth factors, acting singly or in concert. These peptide growth factors also modulate matrix synthesis and degradation, angiogenesis, cell-cell adhesion and cellular metabolism, including lipid uptake. In atherosclerosis, growth factors may be delivered by infiltrating cells or by activation of cells within the artery wall. Normally, growth factors and their cell-surface receptors are expressed at low or undetectable levels. Their up-regulation in early and developing atherosclerotic lesions suggests a pathogenic role for these molecules. Increased levels of isoflavonoids, in particular genistein, which are associated with consumption of soy-based diets, inhibit cell adhesion, alter growth factor activity and inhibit cell proliferation involved in lesion formation.

  6. Omentin attenuates atherosclerotic lesion formation in apolipoprotein E-deficient mice.

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    Hiramatsu-Ito, Mizuho; Shibata, Rei; Ohashi, Koji; Uemura, Yusuke; Kanemura, Noriyoshi; Kambara, Takahiro; Enomoto, Takashi; Yuasa, Daisuke; Matsuo, Kazuhiro; Ito, Masanori; Hayakawa, Satoko; Ogawa, Hayato; Otaka, Naoya; Kihara, Shinji; Murohara, Toyoaki; Ouchi, Noriyuki

    2016-05-01

    Obesity is associated with the development of atherosclerosis. We previously demonstrated that omentin is a circulating adipokine that is downregulated in association with atherosclerotic diseases. Here, we examined the impact of omentin on the development of atherosclerosis with gain-of-function genetic manipulations and dissected its potential mechanism. Apolipoprotein E-deficient (apoE-KO) mice were crossed with transgenic mice expressing the human omentin gene (OMT-Tg) mice in fat tissue to generate apoE-KO/OMT-Tg mice. ApoE-KO/OMT-Tg mice exhibited a significant reduction of the atherosclerotic areas in aortic sinus, compared with apoE-KO mice despite similar lipid levels. ApoE-KO/OMT-Tg mice also displayed significant decreases in macrophage accumulation and mRNA expression of proinflammatory mediators including tumour necrosis factor-α, interleukin-6, and monocyte chemotactic protein-1 in aorta when compared with apoE-KO mice. Treatment of human monocyte-derived macrophages with a physiological concentration of human omentin protein led to reduction of lipid droplets and cholesteryl ester content. Treatment with human omentin protein also reduced lipopolysaccharide-induced expression of proinflammatory genes in human macrophages. Treatment of human macrophages with omentin promoted the phosphorylation of Akt. Inhibition of Akt signalling abolished the anti-inflammatory actions of omentin in macrophages. These data document for the first time that omentin reduces the development of atherosclerosis by reducing inflammatory response of macrophages through the Akt-dependent mechanisms. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  7. CAROTID ATHEROSCLEROTIC LESION IN YOUNG PATIENTS

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    N. V. Pizova

    2014-01-01

    Full Text Available Objective: to determine the incidence of atherosclerotic lesions in the carotid and vertebral arteries of young patients from Doppler ultrasound data and to compare the quantitatively assessed traditional risk factors of coronary heart disease (CHD with severe extracranial artery atherosclerotic lesion.Subjects and methods. Doppler ultrasound was carried out evaluating structural changes in the aortic arch branches in 1563 railway transport workers less than 45 years of age. A separate sample consisted of 68 young people with carotid atherosclerotic changes, in whom traditional risk factors for CHD were studied, so were in a control group of individuals without atherosclerotic changes (n = 38.Results. Among the examinees, carotid atherosclerotic lesion was detected in 112 (7.1 % cases, the increase in the rate of atherosclerotic plaques in patients aged 35–45 years being 9.08 %; that in the rate of local intima-media thickness in those aged 31–40 years being 5.1 %. Smoking (particularly that along with hypercholesterolemia and a family history of cardiovascular diseases, obesity (along with low activity, and emotional overstrain were defined as important risk factors in the young patients. Moreover, factor analysis has shown that smoking,hypertension, and early cardiovascular pathology in the next of kin makes the greatest contribution to the development of carotid atherosclerotic lesion.Conclusion. Among the patients less than 45 years of age, carotid and vertebral artery atherosclerotic changes were found in 112 (7.1 % cases, which were more pronounced in male patients. Smoking, particularly along with hypercholesterolemia and genetic predisposition to cardiovascular diseases, was a risk factor that had the highest impact on the degree of atherosclerotic lesion in the aortic arch branches of the young patients.

  8. Maintenance of Macrophage Redox Status by ChREBP Limits Inflammation and Apoptosis and Protects against Advanced Atherosclerotic Lesion Formation

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    Vincent Sarrazy

    2015-10-01

    Full Text Available Enhanced glucose utilization can be visualized in atherosclerotic lesions and may reflect a high glycolytic rate in lesional macrophages, but its causative role in plaque progression remains unclear. We observe that the activity of the carbohydrate-responsive element binding protein ChREBP is rapidly downregulated upon TLR4 activation in macrophages. ChREBP inactivation refocuses cellular metabolism to a high redox state favoring enhanced inflammatory responses after TLR4 activation and increased cell death after TLR4 activation or oxidized LDL loading. Targeted deletion of ChREBP in bone marrow cells resulted in accelerated atherosclerosis progression in Ldlr−/− mice with increased monocytosis, lesional macrophage accumulation, and plaque necrosis. Thus, ChREBP-dependent macrophage metabolic reprogramming hinders plaque progression and establishes a causative role for leukocyte glucose metabolism in atherosclerosis.

  9. The influence of chronic L-carnitine supplementation on the formation of preneoplastic and atherosclerotic lesions in the colon and aorta of male F344 rats.

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    Empl, Michael T; Kammeyer, Patricia; Ulrich, Reiner; Joseph, Jan F; Parr, Maria K; Willenberg, Ina; Schebb, Nils H; Baumgärtner, Wolfgang; Röhrdanz, Elke; Steffen, Christian; Steinberg, Pablo

    2015-11-01

    L-Carnitine, a key component of fatty acid oxidation, is nowadays being extensively used as a nutritional supplement with allegedly "fat burning" and performance-enhancing properties, although to date there are no conclusive data supporting these claims. Furthermore, there is an inverse relationship between exogenous supplementation and bioavailability, i.e., fairly high oral doses are not fully absorbed and thus a significant amount of carnitine remains in the gut. Human and rat enterobacteria can degrade unabsorbed L-carnitine to trimethylamine or trimethylamine-N-oxide, which, under certain conditions, may be transformed to the known carcinogen N-nitrosodimethylamine. Recent findings indicate that trimethylamine-N-oxide might also be involved in the development of atherosclerotic lesions. We therefore investigated whether a 1-year administration of different L-carnitine concentrations (0, 1, 2 and 5 g/l) via drinking water leads to an increased incidence of preneoplastic lesions (so-called aberrant crypt foci) in the colon of Fischer 344 rats as well as to the appearance of atherosclerotic lesions in the aorta of these animals. No significant difference between the test groups regarding the formation of lesions in the colon and aorta of the rats was observed, suggesting that, under the given experimental conditions, L-carnitine up to a concentration of 5 g/l in the drinking water does not have adverse effects on the gastrointestinal and vascular system of Fischer 344 rats.

  10. DETECTION OF MODIFIED LIPOPROTEINS IN ATHEROSCLEROTIC LESIONS OF HUMAN AORTA

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    P. V. Pigarevsky

    2006-01-01

    Full Text Available Abstract. Specific autoantibodies against acetylated, maleylated and malonic dialdehyde-(MDA-modified lipoproteins are detectable in human plasma. Immunization of rabbits with autologous, correspondingly modified low-density lipoproteins (LDLs did induce autoantibodies against acetylated, maleylated and MDA-modified lipoproteins. In atherosclerotic lesions from hyman aorta, the epitopes have been detected that were recognized by the antibodies to acetylated, maleylated, and MDA-modified LDLs. Such antigens were detected at all atherogenesis stages, beginning with the earliest lesions (lipid spots, and their deposition pattern was quite variable.Rabbit and human autoantibodies against acetylated, maleylated and MDA-modified lipoproteins recognized antigens in human atherosclerotic aorta. Modified proteins were localized both intra- and extracellular in tectum, superficial and deep layers of the atherosclerotic lesions. The most typical mode of depositions for all modified proteins si represented by extracellular deposits in the cap of lipid streaks and fibrous plaques, especially in transitional “shoulder” area.The intimal deposits of modified proteins shared similar features with distribution of apo-B-containing lipoproteins, like as of lipids detectable by Oil Red staining. The areas where modified proteins and apo-B-containing lipoproteins were revealed did often coincide with foci of IgG deposits. Modified proteins were not detectable in the non-affected segments of aortic intima.

  11. Surgical Treatment of Atherosclerotic Lesions of the Subclavian Artery

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    Cohn, Lawrence H.; Fogarty, Thomas J.; Daily, Pat O.; Silverman, James F.; Shumway, Norman E.

    1972-01-01

    Of eight patients with atherosclerotic lesions (seven occlusive, one aneurysmal) of the subclavian artery, five were operated upon because of the subclavian steal and three for severe ischemia of the hand and fingers. Removal or bypass of these lesions was uniformly successful in relieving symptoms. In most cases transcervical carotid-subclavian saphenous vein bypass graft is the treatment of choice, provided no carotid obstruction exists or, if there is obstruction, it can be dealt with at operation. ImagesFigure 1.Figure 2.Figure 3. PMID:4639853

  12. SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice.

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    Zheng, Lingyun; Wu, Teng; Zeng, Cuiling; Li, Xiangli; Li, Xiaoqiang; Wen, Dingwen; Ji, Tianxing; Lan, Tian; Xing, Liying; Li, Jiangchao; He, Xiaodong; Wang, Lijing

    2016-01-01

    Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression. we generated apoE(-/-); SAP(-/-) (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development. SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE(-/-) mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE(-/-) mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages. SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE(-/-) mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Neovascularization of the atherosclerotic plaque: interplay between atherosclerotic lesion, adventitia-derived microvessels and perivascular fat

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    van Hinsbergh, Victor W. M.; Eringa, Etto C.; Daemen, Mat J. A. P.

    2015-01-01

    Neovascularization is a prominent feature in advanced human atherosclerotic plaques. This review surveys recent evidence for and remaining uncertainties regarding a role of neovascularization in atherosclerotic plaque progression. Specific emphasis is given to hypoxia, angiogenesis inhibition, and

  14. Temporal and Quantitative Analysis of Atherosclerotic Lesions in Diet-Induced Hypercholesterolemic Rabbits

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    Qi Yu

    2012-01-01

    Full Text Available The diet-induced atherosclerotic rabbit is an ideal model for atherosclerosis study, but temporal changes in atherosclerotic development in hypercholesterolemic rabbits are poorly understood. Japanese white rabbits were fed a high-cholesterol diet to induce sustained hypercholesterolemia, and each group of 10–12 animals was then sacrificed at 6, 12, 16, or 28 weeks. The rabbit aortas were harvested, and the sizes of the gross and intima atherosclerotic lesions were quantified. The cellular component of macrophages (Mφs and smooth muscle cells (SMCs in aortic intimal lesions was also quantified by immunohistochemical staining, and the correlation between plasma cholesterol levels and the progress of atherosclerotic lesions was studied. The ultrastructure of the atherosclerotic lesions was observed by transmission electron microscopy (TEM. Widely variable atherosclerotic plaques were found from 6 weeks to 28 weeks, and the lesional progress was closely correlated with cholesterol exposure. Interestingly, a relatively reduced accumulation of Mφ, an increased numbers of SMCs, and a damaged endothelial layer were presented in advanced lesions. Moreover, SMCs were closely correlated with cholesterol exposure and lesional progress for the whole period. Cholesterol exposure directly determines atherosclerotic progress in a rabbit model, and the changes in the cellular component of advanced lesions may affect plaque stability in an atherosclerotic rabbit model.

  15. Lack of Atherosclerotic Lesion Progression on Severe Hyperlipidemic Rabbits

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    DIMAS ANDRIANTO

    2009-06-01

    Full Text Available In human, coronary heart disease causes by severe pathological atherosclerosis. In this study, we established animal model to study atherosclerosis caused by hyperlipidemia. This study therefore was undertaken to define the effect of increasing atherosclerosis risk factor, include body weight as well as age, cholesterol concentration and dietary fat in rabbit chow, and time of treatment. Male New Zealand White rabbits were divided into 4 groups; Group I and III were consisted of 2 months rabbit were fed with standard rabbit chow. To introduce atherosclerosis, the chow for Group II was contained 0.25% cholesterol and 5% palm oil; whereas the chow for group IV was contained 0.5% cholesterol and 5% coconut oil to induce higher atherosclerotic lesion. Results showed that group II and IV developed hyperlipidemia. However, aortic cholesterol concentration in those groups did not different significantly (P > 0.05. We suggest that low carbohydrate composition in diet, 50% lower compared to the previous researches, was able to increase high-density lipoprotein (HDL concentration. This study demonstrated the complex interactions between low carbohydrate diet and cholesterol metabolism and the dramatic effects of reducing atherosclerosis risk factor; however, even though hyperlipidemic condition was achieved, total plasma cholesterol HDL ratio was maintained low.

  16. Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions.

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    Onno J de Boer

    Full Text Available BACKGROUND: T cell mediated inflammation contributes to atherogenesis and the onset of acute cardiovascular disease. Effector T cell functions are under a tight control of a specialized T cell subset, regulatory T cells (Treg. At present, nothing is known about the in situ presence of Treg in human atherosclerotic tissue. In the present study we investigated the frequency of naturally occurring Treg cells in all developmental stages of human atherosclerotic lesions including complicated thrombosed plaques. METHODOLOGY: Normal arteries, early lesions (American Heart Association classification types I, II, and III, fibrosclerotic plaques (types Vb and Vc and 'high risk' plaques (types IV, Va and VI were obtained at surgery and autopsy. Serial sections were immunostained for markers specific for regulatory T cells (FOXP3 and GITR and the frequency of these cells was expressed as a percentage of the total numbers of CD3+ T cells. Results were compared with Treg counts in biopsies of normal and inflammatory skin lesions (psoriasis, spongiotic dermatitis and lichen planus. PRINCIPLE FINDINGS: In normal vessel fragments T cells were virtually absent. Treg were present in the intima during all stages of plaque development (0.5-5%. Also in the adventitia of atherosclerotic vessels Treg were encountered, in similar low amounts. High risk lesions contained significantly increased numbers of Treg compared to early lesions (mean: 3.9 and 1.2%, respectively. The frequency of FOXP3+ cells in high risk lesions was also higher compared to stable lesions (1.7%, but this difference was not significant. The mean numbers of intimal FOXP3 positive cells in atherosclerotic lesions (2.4% was much lower than those in normal (24.3% or inflammatory skin lesions (28%. CONCLUSION: Low frequencies of Treg in all developmental stages of human plaque formation could explain the smoldering chronic inflammatory process that takes place throughout the longstanding course of

  17. The collagen cross-linking enzyme lysyl oxidase is associated with the healing of human atherosclerotic lesions.

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    Ovchinnikova, O A; Folkersen, L; Persson, J; Lindeman, J H N; Ueland, T; Aukrust, P; Gavrisheva, N; Shlyakhto, E; Paulsson-Berne, G; Hedin, U; Olofsson, P S; Hansson, G K

    2014-11-01

    Acute clinical complications of atherosclerosis such as myocardial infarction (MI) and ischaemic stroke are usually caused by thrombus formation on the ruptured plaque surface. Collagen, the main structural protein of the fibrous cap, provides mechanical strength to the atherosclerotic plaque. The integrity of the fibrous cap depends on collagen fibre cross-linking, a process controlled by the enzyme lysyl oxidase (LOX). We studied atherosclerotic plaques from human carotid endarterectomies. LOX was strongly expressed in atherosclerotic lesions and detected in the regions with ongoing fibrogenesis. Higher LOX levels were associated with a more stable phenotype of the plaque. In the studied population, LOX mRNA levels in carotid plaques predicted the risk for future MI. Within the lesion, LOX mRNA levels correlated positively with levels of osteoprotegerin (OPG) and negatively with markers of immune activation. The amount of LOX-mediated collagen cross-links in plaques correlated positively also with serum levels of OPG. Lysyl oxidase may contribute to the healing of atherosclerotic lesions and to the prevention of its lethal complications. Mediators of inflammation may control LOX expression in plaques and hence plaque stability. © 2014 The Association for the Publication of the Journal of Internal Medicine.

  18. BCG lowers plasma cholesterol levels and delays atherosclerotic lesion progression in mice.

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    van Dam, Andrea D; Bekkering, Siroon; Crasborn, Malou; van Beek, Lianne; van den Berg, Susan M; Vrieling, Frank; Joosten, Simone A; van Harmelen, Vanessa; de Winther, Menno P J; Lütjohann, Dieter; Lutgens, Esther; Boon, Mariëtte R; Riksen, Niels P; Rensen, Patrick C N; Berbée, Jimmy F P

    2016-08-01

    Bacille-Calmette-Guérin (BCG), prepared from attenuated live Mycobacterium bovis, modulates atherosclerosis development as currently explained by immunomodulatory mechanisms. However, whether BCG is pro- or anti-atherogenic remains inconclusive as the effect of BCG on cholesterol metabolism, the main driver of atherosclerosis development, has remained underexposed in previous studies. Therefore, we aimed to elucidate the effect of BCG on cholesterol metabolism in addition to inflammation and atherosclerosis development in APOE*3-Leiden.CETP mice, a well-established model of human-like lipoprotein metabolism. Hyperlipidemic APOE*3-Leiden.CETP mice were fed a Western-type diet containing 0.1% cholesterol and were terminated 6 weeks after a single intravenous injection with BCG (0.75 mg; 5 × 10(6) CFU). BCG-treated mice exhibited hepatic mycobacterial infection and hepatomegaly. The enlarged liver (+53%, p = 0.001) coincided with severe immune cell infiltration and a higher cholesterol content (+31%, p = 0.03). Moreover, BCG reduced plasma total cholesterol levels (-34%, p = 0.003), which was confined to reduced nonHDL-cholesterol levels (-36%, p = 0.002). This was due to accelerated plasma clearance of cholesterol from intravenously injected [(14)C]cholesteryl oleate-labelled VLDL-like particles (t½ -41%, p = 0.002) as a result of elevated hepatic uptake (+25%, p = 0.05) as well as reduced intestinal cholestanol and plant sterol absorption (up to -37%, p = 0.003). Ultimately, BCG decreased foam cell formation of peritoneal macrophages (-18%, p = 0.02) and delayed atherosclerotic lesion progression in the aortic root of the heart. BCG tended to decrease atherosclerotic lesion area (-59%, p = 0.08) and reduced lesion severity. BCG reduces plasma nonHDL-cholesterol levels and delays atherosclerotic lesion formation in hyperlipidemic mice. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles

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    Current approaches to the diagnosis and therapy of atherosclerosis cannot target to lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing in...

  20. Bone Like Arterial Calcification in Femoral Atherosclerotic Lesions: Prevalence and Role of Osteoprotegerin and Pericytes.

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    Davaine, J-M; Quillard, T; Chatelais, M; Guilbaud, F; Brion, R; Guyomarch, B; Brennan, M Á; Heymann, D; Heymann, M-F; Gouëffic, Y

    2016-02-01

    Arterial calcification, a process that mimics bone formation, is an independent risk factor of cardiovascular morbidity and mortality, and has a significant impact on surgical and endovascular procedures and outcomes. Research efforts have focused mainly on the coronary arteries, while data regarding the femoral territory remain scarce. Femoral endarterectomy specimens, clinical data, and plasma from a cohort of patients were collected prospectively. Histological analysis was performed to characterize the cellular populations present in the atherosclerotic lesions, and that were potentially involved in the formation of bone like arterial calcification known as osteoid metaplasia (OM). Enzyme linked immunosorbent assays and cell culture assays were conducted in order to understand the cellular and molecular mechanisms underlying the formation of OM in the lesions. Twenty-eight of the 43 femoral plaques (65%) displayed OM. OM included osteoblast and osteoclast like cells, but very few of the latter exhibited the functional ability to resorb mineral tissue. As in bone, osteoprotegerin (OPG) was significantly associated with the presence of OM (p = .04). Likewise, a high plasma OPG/receptor activator for the nuclear factor kappa B ligand (RANKL) ratio was significantly associated with the presence of OM (p = .03). At the cellular level, there was a greater presence of pericytes in OM+ compared with OM- lesions (5.59 ± 1.09 vs. 2.42 ± 0.58, percentage of area staining [region of interest]; p = .04); in vitro, pericytes were able to inhibit the osteoblastic differentiation of human mesenchymal stem cells, suggesting that they are involved in regulating arterial calcification. These results suggest that bone like arterial calcification (OM) is highly prevalent at femoral level. Pericyte cells and the OPG/RANK/RANKL triad seem to be critical to the formation of this ectopic osteoid tissue and represent interesting potential therapeutic targets to reduce the clinical

  1. Protective effect of policosanol on atherosclerotic lesions in rabbits with exogenous hypercholesterolemia

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    Arruzazabala M.L.

    2000-01-01

    Full Text Available Policosanol is a mixture of higher aliphatic alcohols purified from sugar cane wax, with cholesterol-lowering effects demonstrable in experimental models and in patients with type II hypercholesterolemia. The protective effects of policosanol on atherosclerotic lesions experimentally induced by lipofundin in rabbits and rats and spontaneously developed in stumptail monkeys have been described. The present study was conducted to determine whether policosanol administered orally to rabbits with exogenous hypercholesterolemia also protects against the development of atherosclerotic lesions. Male New Zealand rabbits weighing 1.5 to 2 kg were randomly divided into three experimental groups which received 25 or 200 mg/kg policosanol (N = 7 orally for 60 days with acacia gum as vehicle or acacia gum alone (control group, N = 9. All animals received a cholesterol-rich diet (0.5% during the entire period. Control animals developed marked hypercholesterolemia, macroscopic lesions and arterial intimal thickening. Intima thickness was significantly less (32.5 ± 7 and 25.4 ± 4 µm in hypercholesterolemic rabbits treated with policosanol than in controls (57.6 ± 9 µm. In most policosanol-treated animals, atherosclerotic lesions were not present, and in others, thickness of fatty streaks had less foam cell layers than in controls. We conclude that policosanol has a protective effect on the atherosclerotic lesions occurring in this experimental model.

  2. Activation of calpain-1 in human carotid artery atherosclerotic lesions

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    Pedro Luis M

    2009-06-01

    Full Text Available Abstract Background In a previous study, we observed that oxidized low-density lipoprotein-induced death of endothelial cells was calpain-1-dependent. The purpose of the present paper was to study the possible activation of calpain in human carotid plaques, and to compare calpain activity in the plaques from symptomatic patients with those obtained from patients without symptoms. Methods Human atherosclerotic carotid plaques (n = 29, 12 associated with symptoms were removed by endarterectomy. Calpain activity and apoptosis were detected by performing immunohistochemical analysis and TUNEL assay on human carotid plaque sections. An antibody specific for calpain-proteolyzed α-fodrin was used on western blots. Results We found that calpain was activated in all the plaques and calpain activity colocalized with apoptotic cell death. Our observation of autoproteolytic cleavage of the 80 kDa subunit of calpain-1 provided further evidence for enzyme activity in the plaque samples. When calpain activity was quantified, we found that plaques from symptomatic patients displayed significantly lower calpain activity compared with asymptomatic plaques. Conclusion These novel results suggest that calpain-1 is commonly active in carotid artery atherosclerotic plaques, and that calpain activity is colocalized with cell death and inversely associated with symptoms.

  3. Endothelial lipase is highly expressed in macrophages in advanced human atherosclerotic lesions

    DEFF Research Database (Denmark)

    Bartels, Emil D; Nielsen, John E; Lindegaard, Marie Louise Skakkebæk

    2007-01-01

    Endothelial lipase (EL) is expressed in endothelial cells, and affects plasma lipoprotein metabolism by hydrolyzing phospholipids in HDL. To determine the cellular expression of EL mRNA and protein in human atherosclerotic lesions, we performed in situ hybridization and immunohistochemical studies...

  4. Simulated characterization of atherosclerotic lesions in the coronary arteries by measurement of bioimpedance.

    Science.gov (United States)

    Stiles, David K; Oakley, Barbara

    2003-07-01

    FEM software was used to determine the feasibility of characterizing various types of atherosclerotic lesions in vivo. This was accomplished by simulating two electrodes as being attached to an angioplasty balloon in the coronary artery. The electrodes on the "balloon" touched and measured the simulated complex impedance of type III, IV, and Va and Vb lesions, as defined by the American Heart Association (AHA). Additionally, the effect of changes in morphology on the complex impedance was determined for type Va and Vb lesions. The simulations showed that the layer closest to the electrodes had the most significant effect on the measured complex impedance. As a consequence of these simulations, it appears plausible that electrodes could be placed in vivo to determine the characteristics and type of a given atherosclerotic lesion.

  5. Prediction of Coronary Atherosclerotic Ostial Lesion with a Damping of the Pressure Tracing during Diagnostic Coronary Angiography.

    Science.gov (United States)

    Her, Ae Young; Ann, Soe Hee; Singh, Gillian Balbir; Kim, Yong Hoon; Koo, Bon Kwon; Shin, Eun Seok

    2016-01-01

    When performing coronary angiography (CAG), diagnostic catheter intubation to the ostium can cause damping of the pressure tracing. The aim of this study was to determine the predictors of atherosclerotic ostial stenosis in patients showing pressure damping during CAG. In total, 2926 patients who underwent diagnostic CAG were screened in this study. Pressure damping was defined as an abrupt decline of the coronary blood pressure with a blunted pulse pressure after engagement of the diagnostic catheter. According to CAG and intravascular ultrasound (IVUS), we divided damped ostia into two groups: atherosclerotic ostial lesion group (true lesion group) and non-atherosclerotic ostium group (false lesion group). Clinical and angiographic characteristics were compared between the two groups. The overall incidence of pressure damping was 2.3% (68 patients and 76 ostia). Among the pressure damped ostia, 40.8% (31 of 76 ostia) were true atherosclerotic ostial lesions (true lesion group). The true lesion group had more frequent left main ostial damping and more percutaneous coronary interventions (PCIs) performed on non-ostial lesions, compared to the false lesion group. On multivariate logistic regression analysis, left main ostial damping [hazard ratio (HR) 4.11, 95% confidence interval (CI) 1.24-13.67, p=0.021] and PCI on non-ostial lesion (HR 5.34, 95% CI 1.34-21.27, p=0.018) emerged as independent predictors for true atherosclerotic ostial lesions in patients with pressure damping. Left main ostial damping and the presence of a non-ostial atherosclerotic lesion may suggest a significant true atherosclerotic lesion in the coronary ostium.

  6. Human Alternative Macrophages Populate Calcified Areas of Atherosclerotic Lesions and Display Impaired RANKL-Induced Osteoclastic Bone Resorption Activity.

    Science.gov (United States)

    Chinetti-Gbaguidi, Giulia; Daoudi, Mehdi; Rosa, Mickael; Vinod, Manjula; Louvet, Loïc; Copin, Corinne; Fanchon, Mélanie; Vanhoutte, Jonathan; Derudas, Bruno; Belloy, Loic; Haulon, Stephan; Zawadzki, Christophe; Susen, Sophie; Massy, Ziad A; Eeckhoute, Jérôme; Staels, Bart

    2017-06-23

    Vascular calcification is a process similar to bone formation leading to an inappropriate deposition of calcium phosphate minerals in advanced atherosclerotic plaques. Monocyte-derived macrophages, located in atherosclerotic lesions and presenting heterogeneous phenotypes, from classical proinflammatory M1 to alternative anti-inflammatory M2 macrophages, could potentially display osteoclast-like functions. To characterize the phenotype of macrophages located in areas surrounding the calcium deposits in human atherosclerotic plaques. Macrophages near calcium deposits display an alternative phenotype being both CD68 and mannose receptor-positive, expressing carbonic anhydrase type II, but relatively low levels of cathepsin K. In vitro interleukin-4-polarization of human primary monocytes into macrophages results in lower expression and activity of cathepsin K compared with resting unpolarized macrophages. Moreover, interleukin-4 polarization lowers expression levels of the osteoclast transcriptional activator nuclear factor of activated T cells type c-1, associated with increased gene promoter levels of the transcriptional repression mark H3K27me3 (histone 3 lysine 27 trimethylation). Despite higher expression of the receptor activator of nuclear factor κB receptor, receptor activator of nuclear factor κB ligand/macrophage colony-stimulating factor induction of nuclear factor of activated T cells type c-1 and cathepsin K expression is defective in these macrophages because of reduced Erk/c-fos-mediated downstream signaling resulting in impaired bone resorption capacity. These results indicate that macrophages surrounding calcium deposits in human atherosclerotic plaques are phenotypically defective being unable to resorb calcification. © 2017 American Heart Association, Inc.

  7. Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins.

    Science.gov (United States)

    Zhang, Wenli; He, Hongliang; Liu, Jianping; Wang, Ji; Zhang, Suyang; Zhang, Shuangshuang; Wu, Zimei

    2013-01-01

    High density lipoproteins (HDL) have been successfully reconstructed to deliver a large number of lipophilic drugs. Here, discoidal and spherical recombinant HDL loaded with cardiovascular drug tanshinone IIA (TA) were constructed (TA-d-rHDL and TA-s-rHDL), respectively. And next their in vitro physiochemical and biomimetic properties were characterized. Furthermore, pharmacokinetics, atherosclerotic lesions targeting effects and antiatherogenic efficacies were elaborately performed and compared in atherosclerotic New Zealand White (NZW) rabbits. In vitro characterizations results showed that both TA-d-rHDL and TA-s-rHDL had nano-size diameter, high entrapment efficiency (EE) and drug-loading capacity (DL). Additionally, similar to their native counterparts, TA-d-rHDL maintained remodeling behaviors induced by lecithin cholesterol acyltransferase (LCAT), and TA leaked during remodeling behaviors. Pharmacokinetic studies manifested that both TA-d-rHDL and TA-s-rHDL markedly improved pharmacokinetic behaviors of TA in vivo. Ex vivo imaging demonstrated that both d-rHDL and s-rHDL bound more avidly to atherosclerotic lesions than to normal vessel walls, and s-rHDL had better targeting effect than d-rHDL. Pharmacodynamic tests illustrated that both TA-d-rHDL and TA-s-rHDL had much stronger antiatherogenic efficacies than conventional TA nanostructured lipid carriers (TA-NLC), TA liposomes (TA-L) and commercially available preparation Sulfotanshinone Sodium Injection (SSI). Moreover, TA-s-rHDL had more potent antiatherogenic efficacies than TA-d-rHDL. Collectively our studies indicated that rHDL could be exploited as potential delivery vehicles of TA targeting atherosclerotic lesions as well as synergistically improving efficacies, especially for s-rHDL. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

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    Rosa Sessa

    2013-07-01

    Full Text Available Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development.

  9. Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

    Science.gov (United States)

    Di Pietro, Marisa; Filardo, Simone; De Santis, Fiorenzo; Sessa, Rosa

    2013-01-01

    Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development. PMID:23877837

  10. P2Y6 receptor potentiates pro-inflammatory responses in macrophages and exhibits differential roles in atherosclerotic lesion development.

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    Ricardo A Garcia

    Full Text Available BACKGROUND: P2Y(6, a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y(6 deficiency on atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Cell-based studies in 1321N1 astrocytoma cells, which lack functional P2Y(6 receptors, showed that exogenous expression of P2Y(6 induces a robust, receptor- and agonist-dependent secretion of inflammatory mediators IL-8, IL-6, MCP-1 and GRO1. P2Y(6-mediated inflammatory responses were also observed, albeit to a lesser extent, in macrophages endogenously expressing P2Y(6 and in acute peritonitis models of inflammation. To evaluate the role of P2Y(6 in atherosclerotic lesion development, we used P2Y(6-deficient mice in three mouse models of atherosclerosis. A 43% reduction in aortic arch plaque was observed in high fat-fed LDLR knockout mice lacking P2Y(6 receptors in bone marrow-derived cells. In contrast, no effect on lesion development was observed in fat-fed whole body P2Y(6xLDLR double knockout mice. Interestingly, in a model of enhanced vascular inflammation using angiotensin II, P2Y(6 deficiency enhanced formation of aneurysms and exhibited a trend towards increased atherosclerosis in the aorta of LDLR knockout mice. CONCLUSIONS: P2Y(6 receptor augments pro-inflammatory responses in macrophages and exhibits a pro-atherogenic role in hematopoietic cells. However, the overall impact of whole body P2Y(6 deficiency on atherosclerosis appears to be modest and could reflect additional roles of P2Y(6 in vascular disease pathophysiologies, such as aneurysm formation.

  11. Myocardial perfusion scintigraphy fi ndings in patients with mild coronary atherosclerotic lesions on coronary angiography

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    Zeki Dostbil

    2010-09-01

    Full Text Available Objectives: Myocardial perfusion scintigraphy (MPS iswidely used in functional assessment of myocardial per-fusion. But, some study results are in contradiction withseverity of coronary artery disease detected by coronaryangiography (CA. It is frequently encountered case thatCA is completely normal whereas MPS describes isch-emia. In this study, we aimed to investigate whether mildatherosclerotic lesions cause ischemia.Materials and methods: MPS with 99mTc-MIBI was per-formed in 52 patients who applied to cardiology clinics forhistory of chest pain and underwent diagnostic CA within3 months.Results: In 22 of 52 patients with mild atherosclerotic le-sions, ischemia in various degrees was detected on MPS.In statistical analysis, any signifi cant relationship was notfound between ischemia and gender, hypertension, DM,dyslipidemia, smoking, mitral valve insuffi ciency, left ven-tricular hypertrophy, exercise testing result and affectedcoronary artery.Conclusion: Our study fi ndings have shown that mild ath-erosclerotic lesions even at very early stage may causemyocardial ischemia

  12. Expression of ACAT-1 protein in human atherosclerotic lesions and cultured human monocytes-macrophages.

    Science.gov (United States)

    Miyazaki, A; Sakashita, N; Lee, O; Takahashi, K; Horiuchi, S; Hakamata, H; Morganelli, P M; Chang, C C; Chang, T Y

    1998-10-01

    The acyl coenzyme A:cholesterol acyltransferase (ACAT) gene was first cloned in 1993 (Chang et al, J Biol Chem. 1993;268:20747-20755; designated ACAT-1). Using affinity-purified antibodies raised against the N-terminal portion of human ACAT-1 protein, we performed immunohistochemical localization studies and showed that the ACAT-1 protein was highly expressed in atherosclerotic lesions of the human aorta. We also performed cell-specific localization studies using double immunostaining and showed that ACAT-1 was predominantly expressed in macrophages but not in smooth muscle cells. We then used a cell culture system in vitro to monitor the ACAT-1 expression in differentiating monocytes-macrophages. The ACAT-1 protein content increased by up to 10-fold when monocytes spontaneously differentiated into macrophages. This increase occurred within the first 2 days of culturing the monocytes and reached a plateau level within 4 days of culturing, indicating that the increase in ACAT-1 protein content is an early event during the monocyte differentiation process. The ACAT-1 protein expressed in the differentiating monocytes-macrophages was shown to be active by enzyme assay in vitro. The high levels of ACAT-1 present in macrophages maintained in culture can explain the high ACAT-1 contents found in atherosclerotic lesions. Our results thus support the idea that ACAT-1 plays an important role in differentiating monocytes and in forming macrophage foam cells during the development of human atherosclerosis.

  13. Cholesteryl ester transfer protein expression prevents diet-induced atherosclerotic lesions in male db/db mice.

    Science.gov (United States)

    MacLean, Paul S; Bower, Joseph F; Vadlamudi, Satyaprasad; Osborne, Jody N; Bradfield, John F; Burden, Hubert W; Bensch, William H; Kauffman, Raymond F; Barakat, Hisham A

    2003-08-01

    Accompanying more atherogenic lipoprotein profiles and an increased incidence of atherosclerosis, plasma cholesteryl ester transfer protein (CETP) is depressed in diabetic obese patients compared with nondiabetic obese counterparts. The depressed levels of CETP in the plasma of diabetic obese individuals may contribute to the development of an atherogenic lipoprotein profile and atherogenesis. We have examined the effect of CETP expression on vascular health in the db/db model of diabetic obesity. Transgenic mice expressing the human CETP minigene were crossed with db/db strain, and 3 groups of offspring (CETP, db, and db/CETP) were placed on an atherogenic diet for 16 weeks. The proximal aorta was then excised and examined for the presence of atherosclerotic plaques. In db mice, 9 of 11 had intimal lesions with a mean area of 26 098+/-7486 microm2. No lesions greater than 1000 microm2 were observed in db/CETP or CETP mice. CETP-expressing mice had lower circulating cholesterol concentrations than db mice. Fractionating plasma lipids by FPLC indicated that the difference in total cholesterol was primarily attributable to differences in VLDL and LDL. The expression of human CETP in db/db mice prevented the formation of diet-induced lesions, suggesting an antiatherogenic effect of CETP in the context of diabetic obesity.

  14. A new murine model of stress-induced complex atherosclerotic lesions

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    Amir H. Najafi

    2013-03-01

    The primary purpose of this investigation was to determine whether ApoE−/− mice, when subjected to chronic stress, exhibit lesions characteristic of human vulnerable plaque and, if so, to determine the time course of such changes. We found that the lesions were remarkably similar to human vulnerable plaque, and that the time course of lesion progression raised interesting insights into the process of plaque development. Lard-fed mixed-background ApoE−/− mice exposed to chronic stress develop lesions with large necrotic core, thin fibrous cap and a high degree of inflammation. Neovascularization and intraplaque hemorrhage are observed in over 80% of stressed animals at 20 weeks of age. Previously described models report a prevalence of only 13% for neovascularization observed at a much later time point, between 36 and 60 weeks of age. Thus, our new stress-induced model of advanced atherosclerotic plaque provides an improvement over what is currently available. This model offers a tool to further investigate progression of plaque phenotype to a more vulnerable phenotype in humans. Our findings also suggest a possible use of this stress-induced model to determine whether therapeutic interventions have effects not only on plaque burden, but also, and importantly, on plaque vulnerability.

  15. Neoatherosclerosis: Coronary stents seal atherosclerotic lesions but result in making a new problem of atherosclerosis.

    Science.gov (United States)

    Komiyama, Hidenori; Takano, Masamichi; Hata, Noritake; Seino, Yoshihiko; Shimizu, Wataru; Mizuno, Kyoichi

    2015-11-26

    Chronic inflammation of the native vessel wall with infiltration of lipid-laden foamy macrophages through impaired endothelium results in atherosclerosis. Percutaneous coronary intervention, including metallic stent implantation, is now widely utilized for the treatment of atherosclerotic lesions of the coronary artery. Bare-metal stents and the subsequently developed drug-eluting stents seal the atherosclerosis and resolve lumen stenosis or obstruction of the epicardial coronary artery and myocardial ischemia. After stent implantation, neointima proliferates within the stented segment. Chronic inflammation caused by a foreign body reaction to the implanted stent and subsequent neovascularization, which is characterized by the continuous recruitment of macrophages into the vessel, result in the transformation of the usual neointima into an atheromatous neointima. Neointima with an atherosclerotic appearance, such as that caused by thin-cap fibroatheromas, is now recognized as neoatherosclerosis, which can sometimes cause in-stent restenosis and acute thrombotic occlusion originating from the stent segment following disruption of the atheroma. Neoatherosclerosis is emerging as a new coronary stent-associated problem that has not yet been resolved. In this review article, we will discuss possible mechanisms, clinical challenges, and the future outlook of neoatherosclerosis.

  16. Dotted collar placed around carotid artery induces asymmetric neointimal lesion formation in rabbits without intravascular manipulations

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    Kivelä Antti

    2012-10-01

    Full Text Available Abstract Background Neointimal formation in atherosclerosis has been subject for intense research. However, good animal models mimicking asymmetrical lesion formation in human subjects have been difficult to establish. The aim of this study was to develop a model which would lead to the formation of eccentric lesions under macroscopically intact non-denuded endothelium. Methods We have developed a new collar model where we placed two cushions or dots inside the collar. Arterial lesions were characterized using histology and ultrasound methods. Results When this dotted collar was placed around carotid and femoral arteries it produced asymmetrical pressure on adventitia and a mild flow disturbance, and hence a change in shear stress. Our hypothesis was that this simple procedure would reproducibly produce asymmetrical lesions without any intraluminal manipulations. Intima/media ratio increased towards the distal end of the collar with the direction of blood flow under macroscopically intact endothelium. Macrophages preferentially accumulated in areas of the thickest neointima thus resembling early steps in human atherosclerotic plaque formation. Proliferating cells in these lesions and underlying media were scarce at eight weeks time point. Conclusion The improved dotted collar model produces asymmetrical human-like atherosclerotic lesions in rabbits. This model should be useful in studies regarding the pathogenesis and formation of eccentric atherosclerotic lesions.

  17. Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban

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    Qianxing Zhou

    2011-01-01

    Full Text Available Aim. Thrombin not only plays a central role in thrombus formation and platelet activation, but also in induction of inflammatory processes. Activated factor X (FXa is traditionally known as an important player in the coagulation cascade responsible for thrombin generation. We assessed the hypothesis that rivaroxaban, a direct FXa inhibitor, attenuates plaque progression and promotes stability of advanced atherosclerotic lesions in an in vivo model. Methods and Results. Rivaroxaban (1 or 5 mg/kg body weight/day or standard chow diet was administered for 26 weeks to apolipoprotein E-deficient mice (n=20 per group with already established atherosclerotic lesions. There was a nonsignificant reduction of lesion progression in the high-concentration group, compared to control mice. FXa inhibition with 5 mg Rivaroxaban/kg/day resulted in increased thickness of the protective fibrous caps (12.3±3.8 μm versus 10.1±2.7 μm; P<.05, as well as in fewer medial erosions and fewer lateral xanthomas, indicating plaque stabilizing properties. Real time-PCR from thoracic aortas revealed that rivaroxaban (5 mg/kg/day treatment reduced mRNA expression of inflammatory mediators, such of IL-6, TNF-α, MCP-1, and Egr-1 (P<.05. Conclusions. Chronic administration of rivaroxaban does not affect lesion progression but downregulates expression of inflammatory mediators and promotes lesion stability in apolipoprotein E-deficient mice.

  18. Effects of Mutated Pregnancy-Associated Plasma Protein-A on Atherosclerotic Lesion Development in Mice

    Science.gov (United States)

    Boldt, Henning B.; Bale, Laurie K.; Resch, Zachary T.; Oxvig, Claus; Overgaard, Michael T.

    2013-01-01

    Pregnancy-associated plasma protein-A (PAPP-A) is a large multidomain metalloprotease involved in cleavage of IGF binding protein (IGFBP)-4 and -5 thereby causing release of bioactive IGF. Individual domains of PAPP-A have been characterized in vitro, including the metzincin proteolytic domain important for IGFBP proteolytic activity, short consensus repeats critical for cell surface association, and Lin-12/Notch repeat module demonstrated to determine IGFBP substrate specificity. To test the hypothesis that specific cleavage of IGFBP-4 by PAPP-A in close proximity to the cell surface is required for development of lesions in a murine model of atherosclerosis, the following PAPP-A transgenic (Tg) mice were generated: TgE483A, which lacks all PAPP-A proteolytic activity; TgD1499A, which selectively lacks proteolytic activity against IGFBP-4; and TgK1296A/K1316A, in which cell surface binding is compromised. Following cross-breeding with apolipoprotein E (ApoE) knockout (KO) mice, ApoE KO/Tg mice were fed a high-fat diet to promote aortic lesion development. Lesion area was increased 2-fold in aortas from ApoE KO/Tg wild-type compared with ApoE KO mice (P PAPP-A proteolytic activity is required for the lesion-promoting effect of PAPP-A and that its specificity must be directed against IGFBP-4. Furthermore, our data demonstrate that cleavage of IGFBP-4 at a distance from the cell surface, and hence from the IGF receptor, is not effective in promoting the development of the atherosclerotic lesions. Thus, PAPP-A exerts its effect while bound to the cell surface in vivo. PMID:23161866

  19. The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II-induced atherosclerosis in mice

    DEFF Research Database (Denmark)

    Wintmo, P.; Johansen, Søren Høyer; Hansen, P. B L

    2017-01-01

    Aim: The water channel aquaporin 1 (AQP1) promotes endothelial cell migration. It was hypothesized that AQP1 promotes neovascularization and growth of atherosclerotic plaques. Methods: AQP1 immunoreactivity and protein abundance was examined in human and murine atherosclerotic lesions and aortic...

  20. Combined treatment with olmesartan medoxomil and amlodipine besylate attenuates atherosclerotic lesion progression in a model of advanced atherosclerosis

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    Sievers P

    2015-07-01

    Full Text Available Philipp Sievers,1 Lorenz Uhlmann,2 Sevil Korkmaz-Icöz,3 Christian Fastner,1 Florian Bea,1 Erwin Blessing,1 Hugo A Katus,1 Michael R Preusch11Department of Internal Medicine III, 2Institute of Medical Biometry and Informatics, 3Department of Cardiac Surgery, University of Heidelberg, Heidelberg, GermanyIntroduction: Besides their blood pressure-lowering effects, olmesartan medoxomil and amlodipine besylate exhibit additional anti-inflammatory mechanisms in atherosclerosic disease. Most of the studies investigating the effects of atherosclerosis focused on early atherosclerotic lesions, whereas lesions in human disease, at the time when medical treatment is started, are already well established. Therefore, we set up a model of advanced atherosclerosis and investigated the effects of olmesartan medoxomil, amlodipine besylate, and the combination of both on atherosclerotic lesion size and lesion composition.Materials and methods: Olmesartan medoxomil (1 mg/kg/day, amlodipine besylate (1.5 mg/kg/day, and the combination of both was added to chow and was fed to apolipoprotein E-deficient (ApoE-/- mice at 25 weeks of age. Mice were sacrificed after 25 weeks of drug administration and perfused with formalin. Innominate arteries were dissected out and paraffin embedded. Serial sections were generated, and lesion sizes and their composition – such as minimal thickness of the fibrous cap, size of the necrotic core, and presence of calcification – were analyzed. Electrophoretic mobility shift assays were used to detect DNA-binding activity of the transcription factor nuclear factor-kappa B (NF-κB in aortic tissue.Results: Treatment with the combination of olmesartan medoxomil and amlodipine besylate led to a significant reduction in atherosclerotic lesion size in ApoE-/- mice (olmesartan medoxomil/amlodipine besylate: 122,277±6,795 µm2, number [n]=14; versus control: 177,502±10,814 µm2, n=9; P<0.001. Treatment with amlodipine besylate (n=5 alone

  1. Identification of 92-kD gelatinase in human coronary atherosclerotic lesions. Association of active enzyme synthesis with unstable angina.

    Science.gov (United States)

    Brown, D L; Hibbs, M S; Kearney, M; Loushin, C; Isner, J M

    1995-04-15

    Acute coronary ischemia is usually initiated by rupture of atherosclerotic plaque, leading to intracoronary thrombosis and clinical sequelae. The proximate cause of plaque rupture is unknown. Accordingly, we investigated the potential role of the 92-kD gelatinase member of the matrix metalloproteinase family in acute coronary ischemia. Coronary atherectomy specimens from patients with atherosclerosis and an acute ischemic syndrome consistent with recent plaque rupture (unstable angina) (n = 12) were immunostained for the presence of 92-kD gelatinase; the results were compared with those obtained by identical study of atherectomy specimens from patients with atherosclerosis and angina but without acute ischemia (stable angina) (n = 12). Positive immunostaining for 92-kD gelatinase was present in 83% of specimens from both unstable and stable angina patients. However, intracellular localization of enzyme (indicating active synthesis) was documented in 10 of 10 positively stained specimens from patients with unstable angina compared with 3 of 10 positively stained specimens from patients with stable angina. Macrophages and smooth muscle cells were the major sources of 92-kD gelatinase in all specimens examined by immunostaining of adjacent sections. 92-kD gelatinase is commonly expressed in coronary arterial atherosclerotic lesions. Active synthesis of 92-kD gelatinase by macrophages and smooth muscle cells in atherosclerotic lesions may play a pathogenic role in the development of acute coronary ischemia.

  2. Salidroside Decreases Atherosclerotic Plaque Formation in Low-Density Lipoprotein Receptor-Deficient Mice

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    Bu-Chun Zhang

    2012-01-01

    Full Text Available Salidroside is isolated from Rhodiola rosea and is one of the main active components in Rhodiola species. The present study was designed to evaluate the effects of Salidroside on atherosclerotic plaque formation in high-fat diet-(HFD- fed female LDL receptor knockout (LDLr-/- mice. LDLr-/- mice fed an atherogenic HFD for 12 weeks were divided into two groups. One group was administered Salidroside (50 mg/kg/oral gavage daily for 8 weeks, while the control group was administered saline. Salidroside treatment reduced serum lipids levels and the plaque area through the arch to the abdominal aorta. Furthermore, Salidroside improved macrophage content and enhanced collagen and smooth muscle cells contents in the aortic sinus. These changes were associated with reduced MCP-1, VCAM-1, and VCAM-1 protein expression in atherosclerotic aortas. All these results suggest that Salidroside decreases atherosclerotic plaques formation via effects on lipid lowering and anti-inflammation in HFD-fed LDLr−/− mice.

  3. Endovascular treatment of isolated atherosclerotic lesions of the infrarenal aorta is technically feasible with acceptable long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Laxdal, E. [Department of Vascular Surgery, Haukeland University Hospital, Bergen (Norway) and Department of Surgical Sciences, University of Bergen, Bergen (Norway)]. E-mail: elin.laxdal@helse-bergen.no; Wirsching, J. [Department of Radiology, Haukeland University Hospital, Bergen (Norway); Jenssen, G.L. [Department of Radiology, Haukeland University Hospital, Bergen (Norway); Pedersen, G. [Department of Vascular Surgery, Haukeland University Hospital, Bergen (Norway); Department of Surgical Sciences, University of Bergen, Bergen (Norway); Aune, S. [Department of Vascular Surgery, Haukeland University Hospital, Bergen (Norway); Daryapeyma, A. [Department of Vascular Surgery, Haukeland University Hospital, Bergen (Norway)

    2007-03-15

    Objectives: To investigate the results of endovascular treatment of symptomatic, atherosclerotic lesions of the infrarenal aorta. Patients and method: This is a retrospective study including 30 procedures performed on 25 patients in the period from 1990 through 2003. There were 16 women (64%) and 9 men, with a mean age of 55 years (range 35-81 years). The indication was disabling intermittent claudication in all cases. Preoperative assessment was done with ankle-arm pressure measurement and angiography. The mean length of the lesions was 2.5 cm (range 1-6 cm). One lesion was a short occlusion and nine were >90% stenoses. The remaining 20 lesions were significant (>70%) stenoses. The procedure was done with PTA alone in 13 cases, and with additional stenting in 17. Results: The procedures were technically successful in 28 cases and clinically successful in all 30. In two cases, a >50% residual stenosis was not dilated further because of stretch pain. The mean observation time was 40 months (range 0-135 months). The primary 2 and 5 year patency rates calculated on basis of intention to treat were 90 and 77%. The primary assisted patency rate was 90% at 2 years and 83% at 5 years. Eight patients developed significant restenosis, of which five were treated with a new endovascular procedure. Two failures were treated conservatively and one with surgical thrombendarterectomy. Conclusion: Endovascular treatment of isolated atherosclerotic lesions of the infrarenal aorta is feasible in patients with suitable anatomy. Clinical success rates are high and long-term patency is good. Complications are few and minor. The majority of failures are amenable to new endovascular treatment.

  4. Polymorphisms in NOS3, MTHFR, APOB and TNF-α Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients

    Science.gov (United States)

    Heidari, Mohammad Mehdi; Khatami, Mehri; Hadadzadeh, Mehdi; Kazemi, Mahbobeh; Mahamed, Sahar; Malekzadeh, Pegah; Mirjalili, Massomeh

    2015-01-01

    Background: Atherosclerosis is a complex multifocal arterial disease involving interactions between multiple genetic and environmental factors. Objectives: In the present study, we investigated the possible association between NOS3 (rs1799983), MTHFR (rs1801133), APOB (rs5742904) and TNF-α (rs361525) polymorphisms and the risk of coronary atherosclerotic lesions in Iranian patients. Patients and Methods: In the case-control study, 108 patients with coronary atherosclerosis disease and 95 control subjects with no family history of cardiovascular disease were enrolled. Genotypes for NOS3, MTHFR, APOB and TNF-α polymorphisms were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Results: We specifically detected the NOS3 TT genotype in 12 patients (11.11%) and did not find the same genotype in any of the controls. The frequencies of T allele in patients and the controls were 24% and 17.8%, respectively. The prevalence of the MTHFR TT genotype was 16.7% in patients and 2.2% in control groups. The prevalence of the APOB-100 (R3500Q) mutation in this patient population was 0%. The frequency of the A allele in the TNF-α gene was 11.1% and 11% in patients and controls, respectively, and the AA genotype was undetected. Conclusions: Our results show a significant association of NOS3 and MTHFR gene polymorphisms with coronary atherosclerotic lesions. Therefore, these variants might influence the risk of coronary artery disease, specifically in the Iranian population. PMID:26878010

  5. Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice after cola beverages drinking.

    Science.gov (United States)

    Otero-Losada, Matilde E; Mc Loughlin, Santiago; Rodríguez-Granillo, Gastón; Müller, Angélica; Ottaviano, Graciela; Moriondo, Marisa; Cutrin, Juan C; Milei, José

    2013-04-01

    (56%, p<0.04). TREATMENT- and age-effects on plaque enlargement were additive. Cola beverages caused atherosclerotic lesions' enlargement with metabolic (C) or non metabolic disturbances (L). ApoE-/- mice were particularly sensitive to L treatment. These findings may likely relate to caramel colorant and non-nutritive sweeteners in cola drinks and have potential implications in particularly sensitive individuals.

  6. miR-143 is involved in endothelial cell dysfunction through suppression of glycolysis and correlated with atherosclerotic plaques formation.

    Science.gov (United States)

    Xu, R-H; Liu, B; Wu, J-D; Yan, Y-Y; Wang, J-N

    2016-10-01

    Atherosclerosis is recognized as a chronic inflammatory disease leading to hardening of the vessel wall and narrowing of arteries. Endothelial cells (ECs) exhibit highly active glycolysis, the dysfunction of which leads to accumulation of lipids in the arterial wall and formation of atherosclerotic plaque. qRT-PCR was performed to compare the deregulated miR-143 between atherosclerotic plaque and normal vessel tissues. The direct target of miR-143 was verified by Western blot and luciferase assay. The metabolic enzymes in atherosclerotic plaque and normal vessel tissues were measured. HUVECs were transfected with miR-143 precursor or control microRNAs, and glucose uptake, lactate production, intracellular ATP, and oxygen consumption were measured. In this study, we report a correlation between up-regulated miR-143, EC dysfunction, and atherosclerotic plaque formation. The glycolysis rate was significantly elevated in ECs, which show relatively low levels of miR-143. Importantly, miR-143 was upregulated in clinical atherosclerotic plaque samples compared with healthy arteries, suggesting that miR-143 might play important roles in the atherosclerotic plaque formation. Moreover, mRNA levels of key enzymes of glycolysis, such as HK2, LDHA, and PKM2 are significantly down-regulated in the atherosclerotic plaque samples. Overexpression of miR-143 in HUVECs suppresses glycolysis through direct targeting of HK2, leading to EC dysfunction. Restoration of HK2 expression rescues glycolysis in miR-143-overexpressing HUVECs. This study provides further insight into the metabolic mechanisms involved in atherosclerotic plaque formation due to microRNAs.

  7. Dietary lutein and fish oil interact to alter atherosclerotic lesions in a Japanese quail model of atherosclerosis.

    Science.gov (United States)

    Shanmugasundaram, R; Selvaraj, R K

    2011-12-01

    Interactions between concentration of dietary lutein and fish oil in diets on atherosclerosis incidences were studied in a cholesterol-induced-atherosclerosis (CIA) model. CIA Japanese quail were fed a basal diet with three amounts of lutein (0, 25 and 50 mg/kg diet) and two amounts of fish oil (3% and 6%) in a 3 × 2 factorial in five replications. Samples were collected at 24 and 27 weeks of age. Atherosclerosis lesions in the dorsal aorta were measured by histochemistry sectioning. At 27 weeks of age, increasing dietary fish oil content to 6% decreased (p < 0.01) the atherosclerotic lesions only in the 0 mg lutein supplemented groups. At 27 weeks of age, increasing dietary fish oil content to 6% increased the atherosclerotic lesion score when lutein was supplemented at either 25 or 50 mg/kg feed. Aorta and liver lutein content increased (p < 0.01) with increasing dietary lutein content at 27 weeks of age. Increasing dietary fish oil content to 6% increased (p < 0.01) the aorta fat content by twofold and decreased (p < 0.01) the liver fat by 26% at 27 weeks of age. Increasing the dietary fish oil content to 6% increased (p = 0.01) the total PUFA and decreased (p = 0.03) the total mono unsaturated fatty acids content of the aorta at 27 weeks of age. At 27 weeks of age, increasing dietary fish oil content to 6% decreased the amount of TBARS (p = 0.01) and IL-1 mRNA (p < 0.01) only in the 0 mg lutein supplemented groups. Increasing dietary fish oil content to 6% increased the amount of TBARS and IL-1 mRNA of the aorta when lutein was supplemented at either 25 or 50 mg/kg diet. Dietary lutein supplementation decreased atherosclerosis lesions only at low levels of dietary polyunsaturated fatty acids. © 2010 Blackwell Verlag GmbH.

  8. Targeting of matrix metalloproteinase activation for noninvasive detection of vulnerable atherosclerotic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hartung, Dagmar [University of California, School of Medicine, Irvine, CA (United States); School of Medicine, Department of Radiology, Hannover (Germany); Schaefers, Michael; Kopka, Klaus [University of Muenster, Department of Nuclear Medicine, Muenster (Germany); Fujimoto, Shinichiro; Narula, Navneet; Petrov, Artiom; Narula, Jagat [University of California, School of Medicine, Irvine, CA (United States); Levkau, Bodo [University of Duisburg-Essen, Institute of Pathophysiology, Duisburg (Germany); Virmani, Renu; Kolodgie, Frank D. [Cardiovascular Pathology, Gaithersburg, MD (United States); Reutelingsperger, Chris; Hofstra, Leo [Cardiovascular Research Institute, Maastricht (Netherlands)

    2007-06-15

    Inflammation plays an important role in vulnerability of atherosclerotic plaques to rupture and hence acute coronary events. The monocyte-macrophage infiltration in plaques leads to upregulation of cytokines and metalloproteinase enzymes. Matrix metalloproteinases result in matrix dissolution and consequently expansive remodeling of the vessel. They also contribute to attenuation of fibrous cap and hence susceptibility to rupture. Assessment of metalloproteinase expression and activity should provide information about plaque instability. (orig.)

  9. Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

    Energy Technology Data Exchange (ETDEWEB)

    Son, Dong Ju [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Kim, Soo Yeon [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Han, Seong Su [University of Iowa Carver College of Medicine, Department of Pathology, Iowa City, IA (United States); Kim, Chan Woo [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Kumar, Sandeep [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Park, Byeoung Soo [Nanotoxtech Co., Ansan (Korea, Republic of); Lee, Sung Eun [Division of Applied Biology and Chemistry, Kyungpook National University, Daegu (Korea, Republic of); Yun, Yeo Pyo [College of Pharmacy, Chungbuk National University, Cheongju (Korea, Republic of); Jo, Hanjoong, E-mail: hjo@emory.edu [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Park, Young Hyun, E-mail: pyh012@sch.ac.kr [Department of Food Science and Nutrition, College of Natural Sciences, Soonchunhyang University, Asan (Korea, Republic of)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

  10. Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jing-Hsien [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Chi-Ping [Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Hui-Hsuan, E-mail: linhh@csmu.edu.tw [Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China)

    2013-10-15

    Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of > 50 μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu{sup 2+}-induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foam cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent. - Highlights: • The anti-atherosclerotic effect of gossypetin in vitro was examined. • Gossypetin inhibited LDL oxidation. • Gossypetin showed potential in reducing on the formation of foam cells. • Gossypetin functions against ox-LDL through PPARa activation and PPARγ depression.

  11. Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits

    Directory of Open Access Journals (Sweden)

    Shoucui Gao

    2017-01-01

    Full Text Available High levels of plasma high-density lipoprotein-cholesterol (HDL-C are inversely associated with the risk of atherosclerosis and other cardiovascular diseases; thus, pharmacological inhibition of cholesteryl ester transfer protein (CETP is considered to be a therapeutic method of raising HDL-C levels. However, many CETP inhibitors have failed to achieve a clinical benefit despite raising HDL-C. In the study, we generated transgenic (Tg rabbits that overexpressed the human CETP gene to examine the influence of CETP on the development of atherosclerosis. Both Tg rabbits and their non-Tg littermates were fed a high cholesterol diet for 16 weeks. Plasma lipids and body weight were measured every 4 weeks. Gross lesion areas of the aortic atherosclerosis along with lesional cellular components were quantitatively analyzed. Overexpression of human CETP did not significantly alter the gross atherosclerotic lesion area, but the number of macrophages in lesions was significantly increased. Overexpression of human CETP did not change the plasma levels of total cholesterol or low-density lipoprotein cholesterol but lowered plasma HDL-C and increased triglycerides. These data revealed that human CETP may play an important role in the development of atherosclerosis mainly by decreasing HDL-C levels and increasing the accumulation of macrophage-derived foam cells.

  12. Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Verschuren, L.; Kleemann, R.; Offerman, E.H.; Szalai, A.J.; Emeis, S.J.; Princen, H.M.G.; Kooistra, T.

    2005-01-01

    Objective - To evaluate whether low-dose atorvastatin suppresses atherosclerotic lesion progression and inflammation in apolipoprotein E*3 (apoE*3)-Leiden mice beyond its cholesterol-lowering effect. Methods and Results - ApoE*3-Leiden mice were fed a high-cholesterol (HC) diet until mild

  13. QUALITY OF LIFE IN PATIENTS WITH HYPERTENSION, CORONARY HEART DISEASE, AND ATHEROSCLEROTIC LESION OF LOWER EXTREMITY ARTERIES IN THE SECONDARY PREVENTION OF COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    A. A. Karlov

    2014-07-01

    Full Text Available Atherosclerotic lesion of lower extremity arteries frequently complicates the long-term course of hypertension and it is generally associated with coronary heart disease. Our study has attempted to evaluate the impact of combination antihypertensive therapy involving amlodipine, bisoprolol, and lisinopril on quality of life in this category of patients.

  14. Transgenic overexpression of pregnancy-associated plasma protein-A in murine arterial smooth muscle accelerates atherosclerotic lesion development

    DEFF Research Database (Denmark)

    Conover, Cheryl A; Mason, Megan A; Bale, Laurie K

    2010-01-01

    Pregnancy-associated plasma protein-A (PAPP-A) increases local IGF-I bioavailability through cleavage of inhibitory IGF binding protein (IGFBP)-4 in a variety of systems, including the cardiovascular system. To test the hypothesis that expression of PAPP-A promotes the development...... of atherosclerotic lesions, we generated transgenic mice that express human PAPP-A in arterial smooth muscle. Four founder lines were characterized for transgenic human PAPP-A mRNA and protein expression, IGFBP-4 protease activity, and tissue specificity. In study I, apolipoprotein E knockout (ApoE KO) mice, a well......-characterized mouse model of atherosclerosis, and ApoE KO mice expressing the human PAPP-A transgene at relatively high levels (ApoE KO/Tg) were fed a high-fat diet. At harvest, aortas were dissected and opened longitudinally for en face staining of lipid-rich lesions. Lesion area was increased 3.5-fold in aortas...

  15. Neither antioxidants nor genistein inhibit the progression of established atherosclerotic lesions in older apoE deficient mice.

    Science.gov (United States)

    Averill, Michelle M; Bennett, Brian J; Rattazzi, Marcello; Rodmyre, Rebecca M; Kirk, Elizabeth A; Schwartz, Stephen M; Rosenfeld, Michael E

    2009-03-01

    Supplements and diets enriched in antioxidants and soy isoflavones are purported to reduce cardiovascular disease risk. Many experimental studies have demonstrated inhibitory effects of antioxidants and soy isoflavones on the development of fatty streaks in animal models. However, it is still unknown whether antioxidants and isoflavones have comparable inhibitory effects on the progression of advanced stages of atherosclerosis. This is an important question because clinical trials in humans have not supported a cardio-protective role for antioxidants or isoflavones. Thus, we examined the effects of antioxidants and genistein on the progression and composition of established, advanced atherosclerotic lesions in the innominate arteries (IA) of older apolipoprotein E-deficient (apoE(-/-)) mice. Thirty-week-old male apoE(-/-) mice were fed chow with or without genistein (0.27%, w/w) for 6, 12 and 24 weeks. Twenty-week-old male apoE(-/-) mice were fed chow with or without a cocktail of antioxidants (vitamin E 0.2%, w/w; vitamin C 0.05%, w/w; and beta carotene 0.5%, w/w) for 10, 16, and 22 weeks. There were no significant differences in total plasma cholesterol, body weight, average lesion or medial area, or changes in lesion composition with either treatment in comparison to control mice.

  16. Dietary Antioxidants and Genistein Do Not Inhibit the Progression of Established Atherosclerotic Lesions in Older Apo E Deficient Mice

    Science.gov (United States)

    Averill, Michelle M.; Bennett, Brian J.; Rattazzi, Marcello; Rodmyre, Rebecca M.; Kirk, Elizabeth A.; Schwartz, Stephen M.; Rosenfeld, Michael E.

    2009-01-01

    Antioxidants and soy isoflavones inhibit the development of fatty streaks in various animal models. However, clinical trials in humans have not entirely supported a cardio-protective role for antioxidants or isoflavones. Thus, we examined the effects of antioxidants and genistein on the progression and composition of established, advanced atherosclerotic lesions in the innominate arteries (IA) of older apolipoprotein E-deficient (apoE-/-) mice. Thirty week old male apoE-/- mice were fed chow with or without genistein (0.27% w/w) for 6, 12 and 24 weeks. Twenty week old male apoE-/- mice were fed chow with or without a cocktail of antioxidants (vitamin E 0.2% w/w, vitamin C 0.05% w/w, and beta carotene 0.5% w/w) for 10, 16, and 22 weeks. There were no significant differences in total plasma cholesterol, body weight, average area of the lesion or media, or changes in lesion composition with either treatment in comparison to chow-fed control mice. This data may help explain why there have not been consistent protective effects of antioxidants and isoflavones on cardiovascular disease in human clinical trials. PMID:18667203

  17. [Atorvastatin inhibits the atherosclerotic lesion induced by tumor necrosis factor-like weak inducer of apoptosis in apolipoprotein E deficient mice].

    Science.gov (United States)

    Fernández-Laso, Valvanera; Sastre, Cristina; Egido, Jesús; Martín-Ventura, Jose L; Blanco-Colio, Luis M

    2015-01-01

    Interaction of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) with its receptor Fn14 accelerates atherosclerotic plaque development in ApoE deficient mice (ApoE KO). In this work, an analysis has been made on the effect of an HMG-CoA reductase inhibitor, atorvastatin, on atherosclerotic plaque development accelerated by TWEAK in ApoE KO mice. Eight week-old ApoE KO mice were fed with a high cholesterol diet for 4 weeks. The animals were then randomized into 3 groups: mice injected i.p. with saline, recombinant TWEAK (10 μg/kg/twice a week), or recombinant TWEAK plus atorvastatin (1 mg/kg/day) for 4 weeks. The lesion size, cellular composition, lipid and collagen content were analyzed, as well as inflammatory response in atherosclerotic plaques present in aortic root of mice. TWEAK treated mice showed an increase in atherosclerotic plaque size, as well as in collagen/lipid ratio compared with control mice. In addition, macrophage content, MCP-1 and RANTES expression, and NF-κB activation were augmented in atherosclerotic plaques present in aortic root of TWEAK treated mice compared with control mice. Treatment with atorvastatin prevented all these changes induced by TWEAK in atherosclerotic lesions. Atorvastatin treatment also decreased Fn14 expression in the atherosclerotic plaques of ApoE KO mice. Atorvastatin prevents the pro-atherogenic effects induced by TWEAK in ApoE KO mice, which could be related to the inhibition of Fn14 expression. The results of this study provide new information on the beneficial effects of statin treatment in cardiovascular diseases. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  18. Enhanced Impact of Cholesterol Absorption Marker on New Atherosclerotic Lesion Progression After Coronary Intervention During Statin Therapy.

    Science.gov (United States)

    Mori, Kenta; Ishida, Tatsuro; Tsuda, Shigeyasu; Oshita, Toshihiko; Shinohara, Masakazu; Hara, Tetsuya; Irino, Yasuhiro; Toh, Ryuji; Hirata, Ken-Ichi

    2017-02-01

    Clinical trials suggest that residual risks remain for coronary artery disease (CAD) during low-density lipoprotein cholesterol (LDL-C) lowering therapy. We aimed to investigate the role of exogenous lipids in the prognosis of CAD after percutaneous coronary intervention (PCI). A total of 145 patients with CAD, who underwent elective PCI, and 82 non-CAD (control) patients were enrolled in this study. CAD patients underwent follow-up coronary angiography 6-9 months after PCI, and were classified into three groups: 1) patients who showed in-stent restenosis (ISR) in the original stented segment, 2) patients with other non-target coronary atherosclerotic lesions (de novo), and 3) patients with neither ISR nor a de novo lesion. Biochemical analyses were performed on fasting serum samples at the time of follow-up coronary angiography. Despite the controlled serum LDL-C levels, CAD patients with statin showed elevated cholesterol absorption marker campesterol/total cholesterol (TC), synthesis marker lathosterol/TC, campesterol/lathosterol ratio, and apolipoprotein B48 (apoB48) concentration compared with non-CAD patients. The high campesterol/TC, campesterol/lathosterol ratio, and apoB48 concentration were associated with de novo lesion progression after PCI. In stepwise multivariate logistic regression analysis, campesterol/TC and apoB48 concentrations were independent risk factors for de novo lesion progression in statin-treated CAD patients after PCI. The increase of cholesterol absorption marker and apoB48 concentration may lead to the progression of de novo lesions, and these markers may represent a residual risk during statin treatment after PCI.

  19. ACAT inhibition reduces the progression of preexisting, advanced atherosclerotic mouse lesions without plaque or systemic toxicity.

    Science.gov (United States)

    Rong, James X; Blachford, Courtney; Feig, Jonathan E; Bander, Ilda; Mayne, Jeffrey; Kusunoki, Jun; Miller, Christine; Davis, Matthew; Wilson, Martha; Dehn, Shirley; Thorp, Edward; Tabas, Ira; Taubman, Mark B; Rudel, Lawrence L; Fisher, Edward A

    2013-01-01

    Acyl-CoA:cholesterol acyltransferase (ACAT) converts cholesterol to cholesteryl esters in plaque foam cells. Complete deficiency of macrophage ACAT has been shown to increase atherosclerosis in hypercholesterolemic mice because of cytotoxicity from free cholesterol accumulation, whereas we previously showed that partial ACAT inhibition by Fujirebio compound F1394 decreased early atherosclerosis development. In this report, we tested F1394 effects on preestablished, advanced lesions of apolipoprotein-E-deficient mice. Apolipoprotein-E-deficient mice on Western diet for 14 weeks developed advanced plaques, and were either euthanized (Baseline), or continued on Western diet with or without F1394 and euthanized after 14 more weeks. F1394 was not associated with systemic toxicity. Compared with the baseline group, lesion size progressed in both groups; however, F1394 significantly retarded plaque progression and reduced plaque macrophage, free and esterified cholesterol, and tissue factor contents compared with the untreated group. Apoptosis of plaque cells was not increased, consistent with the decrease in lesional free cholesterol. There was no increase in plaque necrosis and unimpaired efferocytosis (phagocytic clearance of apoptotic cells). The effects of F1394 were independent of changes in plasma cholesterol levels. Partial ACAT inhibition by F1394 lowered plaque cholesterol content and had other antiatherogenic effects in advanced lesions in apolipoprotein-E-deficient mice without overt systemic or plaque toxicity, suggesting the continued potential of ACAT inhibition for the clinical treatment of atherosclerosis, in spite of recent trial data.

  20. APOE -491 T allele may reduce the risk of atherosclerotic lesions among middle-aged women.

    Science.gov (United States)

    Bañares, Virginia G; Bardach, Ariel; Peterson, Graciela; Tavella, Marcelo J; Schreier, Laura E

    2012-03-01

    Genetic variability of the APOE gene confers susceptibility to coronary artery disease (CAD). Beyond variability on the coding region, polymorphisms in the regulatory region of the APOE gene have been associated with variation on plasma cholesterol levels. It has also been demonstrated a complex and multifactorial association between, APOE gene polymorphisms, gender, plasma lipids levels and risk of CAD. In the present case-control study, we examined polymorphisms -427 T/C and -491 A/T in the promoter region of APOE in relation to lipid profile and the coronary atherosclerosis, in a sample of Argentinean adults with (cases) and without (controls) atherosclerotic injuries regarding gender and age. In females below 60 years APOE -491 T allele was less prevalent in cases than in controls (OR 0.12, 95% CI 0.04-0.76). Among females cases the T allele was more frequent with increasing age (OR 0.49, 95% CI 0.27-0.90). Female up to 45 years who were carriers of the T allele showed lower levels of total (P = 0.01) and LDL cholesterol (P = 0.02) compared with non-carriers. Levels of total and LDL cholesterol increased with the age only in female carriers (P < 0.01 and P < 0.01). No differences were observed for HDL and TG levels. Allele C of polymorphism APOE -427 was associated with higher levels of triglycerides (P < 0.01). We conclude that, in middle-aged women, APOE -491 T allele contributes keeping lower levels of LDL cholesterol in the population studied, and would have a putative protective effect for the development of CAD.

  1. α4β7 Integrin (LPAM-1 is Upregulated at Atherosclerotic Lesions and is Involved in Atherosclerosis Progression

    Directory of Open Access Journals (Sweden)

    Kangkang Zhi

    2014-06-01

    Full Text Available Background/Aims: Integrin activation and lymphocyte migration to the vascular intima is a key event in early atherosclerosis. α4β7 integrin (LPAM-1 and its ligand, mucosal addressin cell adhesion molecule (MAdCAM-1 are known to play an important role in homing of activated lymphocytes to gut-associated lymphoid tissues. However, it is unclear whether α4β7 integrin is involved in the pathogenesis of atherosclerosis. Methods: The expressions of α4β7 integrin and its ligands in atherosclerosis plaques from 12 week high fat diet (HFD fed ApoE-/- and C57BL/6 mice were examined using immunofluorescent and immunohistochemical assays, respectively. We also generated ApoE/β7 double deficient mice and compared atherosclerotic lesion development in β7+/+ApoE-/- and β7-/-ApoE-/- mice that were fed with HFD for 12 weeks. Results: We found an upregulation of α4β7 integrin and its ligands VCAM-1 and MAdCAM-1 at atherosclerosis plaques in Apolipoprotein E deficient (ApoE-/- mice fed with HFD for 12 weeks. Over the 12 week HFD period, peripheral blood lymphocyte (PBL expression of α4β7 integrin increased in parallel with aortic lesion size. A removal of α4β7 integrin by genetic deletion of the β7 chain in the ApoE-/- mouse resulted in a markedly decreased 12 week-HFD atherosclerotic plaque area. β7-/- ApoE-/- macrophages showed reduced acetylated and native LDL uptake and phagocytic activity, revealing possible roles for α4β7 at two distinct stages of macrophage dysfunction during atherogenesis. Finally, a reduced activity of integrin downstream signalling components focal adhesion kinase (FAK and MAPK/ERK1/2 in macrophage indicates their possible engagement during α4β7 integrin signalling in atherosclerosis. Conclusions: Together our results reveal a critical role of α4β7 in diet-induced atherosclerosis in mouse.

  2. SCM-198 attenuates early atherosclerotic lesions in hypercholesterolemic rabbits via modulation of the inflammatory and oxidative stress pathways.

    Science.gov (United States)

    Zhang, Yanfei; Guo, Wei; Wen, Yadan; Xiong, Qinghui; Liu, Hongrui; Wu, Jian; Zou, Yunzeng; Zhu, Yizhun

    2012-09-01

    GPx in the aorta. In a rabbit atherosclerotic model, SCM-198 dose-dependently ameliorated the progression of atherosclerotic lesions and vascular dysfunction accompanied by the suppression of inflammatory factors and oxidative stress. These findings suggested that SCM-198 might be a potential agent for the treatment of atherosclerosis. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Protonated nanostructured aluminosilicate (NSAS reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

    Directory of Open Access Journals (Sweden)

    Constantinides Panayiotis P

    2009-07-01

    Full Text Available Abstract The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w, untreated control and 2% (w/w stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w and stigmastanol at 2% (w/w treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w NSAS and 2% (w/w stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model.

  4. Gadolinium-Functionalized Peptide Amphiphile Micelles for Multimodal Imaging of Atherosclerotic Lesions.

    Science.gov (United States)

    Yoo, Sang Pil; Pineda, Federico; Barrett, John C; Poon, Christopher; Tirrell, Matthew; Chung, Eun Ji

    2016-11-30

    The leading causes of morbidity and mortality globally are cardiovascular diseases, and nanomedicine can provide many improvements including disease-specific targeting, early detection, and local delivery of diagnostic agents. To this end, we designed fibrin-binding, peptide amphiphile micelles (PAMs), achieved by incorporating the targeting peptide cysteine-arginine-glutamic acid-lysine-alanine (CREKA), with two types of amphiphilic molecules containing the gadoliniuim (Gd) chelator diethylenetriaminepentaacetic acid (DTPA), DTPA-bis(stearylamide)(Gd), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(poly(ethylene glycol) (PEG))-2000]-DTPA(Gd) (DSPE-PEG2000-DTPA(Gd)). The material characteristics of the resulting nanoparticle diagnostic probes, clot-binding properties in vitro, and contrast enhancement and safety for dual, optical imaging-magnetic resonance imaging (MRI) were evaluated in the atherosclerotic mouse model. Transmission electron micrographs showed a homogenous population of spherical micelles for formulations containing DSPE-PEG2000-DTPA(Gd), whereas both spherical and cylindrical micelles were formed upon mixing DTPA-BSA(Gd) and CREKA amphiphiles. Clot-binding assays confirmed DSPE-PEG2000-DTPA(Gd)-based CREKA micelles targeted clots over 8-fold higher than nontargeting (NT) counterpart micelles, whereas no difference was found between CREKA and NT, DTPA-BSA(Gd) micelles. However, in vivo MRI and optical imaging studies of the aortas and hearts showed fibrin specificity was conferred by the peptide ligand without much difference between the nanoparticle formulations or shapes. Biodistribution studies confirmed that all micelles were cleared through both the reticuloendothelial system and renal clearance, and histology showed no signs of necrosis. In summary, these studies demonstrate the successful synthesis, and the molecular imaging capabilities of two types of CREKA-Gd PAMs for atherosclerosis. Moreover, we demonstrate the differences in

  5. Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development.

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    Amanda C Foks

    Full Text Available OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. METHODS AND RESULTS: TIGIT was upregulated on CD4(+ T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/- mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. CONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells.

  6. Noninvasive detection of matrix metalloproteinase-9 in atherosclerotic lesions using technetium-99m-labeled single-photon emission computed tomography in vivo.

    Science.gov (United States)

    Wang, Zhongjuan; Deng, Gang; Zhang, Zhuiyang; Huang, Hongbo; Zhao, Yanjun

    2017-04-01

    Previous studies have suggested that matrix metalloproteinase (MMP) inhibitor uptake may offer a precise estimation of MMP activity in atherosclerotic lesions. In this study, we explored the feasibility of noninvasive detection of MMP-9 activity using technetium-99m-labeled matrix metalloproteinase-9 antibody (Tc-McAb) in vivo. ApoE-deficient (ApoE) atherosclerosis mice models (n=10) were induced through a high-cholesterol diet following ligation of their left common carotid artery. After 4 weeks, the models were verified through proton density-weighted and T2-weighted images obtained by MRI. C57BL/6 sham mice (n=8) were used as controls. In addition, normal mice (n=20) were used to characterize blood clearance. After radiolabeled McAb administration, single-photon emission computed tomography (SPECT) was performed. Subsequently, left common carotid arteries were harvested for ex-vivo autoradiograph imaging. Then, morphology and activity assays of MMP-9 were histologically and immunohistochemically examined. MRI showed higher signal intensities in the left common carotid arteries with irregular stenoses in the lumen of blood vessels in atherosclerosis mice models in vivo. Atherosclerotic lesions on left common carotid artery specimens were also clearly visualized using SPECT 2 h after Tc-McAb administration in vivo. Note that the radiochemistry purity of the Tc-McAb used was 85-95%. Biodistribution studies have shown that the clearance of Tc-McAb from blood was rapid. In addition, atherosclerotic lesions were clearly visualized on radioautography film shadows ex vivo. MMP-9 activities within the atherosclerotic lesions were noninvasively detected using Tc-labeled SPECT in vivo.

  7. Darbepoetin alpha reduces oxidative stress and chronic inflammation in atherosclerotic lesions of apo E deficient mice in experimental renal failure.

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    Nicole Arend

    Full Text Available BACKGROUND: Cardiovascular morbidity and mortality is very important in patients with chronic renal failure. This occurs even in mild impairment of renal function and may be related to oxidative stress and chronic inflammation. The nephrectomized apo E knockout mouse is an accepted model for evaluating atherosclerosis in renal dysfunction. Erythropoietin derivates showed anti-oxidative and anti-inflammatory effects. Therefore, this study evaluates the effects of Darbepoetin on markers of oxidative stress and chronic inflammation in atherosclerotic lesions in apo E knockout mice with renal dysfunction. METHODS: Apo E knockout mice underwent unilateral (Unx, n = 20 or subtotal (Snx, n = 26 nephrectomy or sham operation (Sham, n = 16. Mice of each group were either treated with Darbepoetin or saline solution, a part of Snx mice received a tenfold higher dose of Darbepoetin. The aortic plaques were measured and morphologically characterized. Additional immunhistochemical analyses were performed on tissue samples taken from the heart and the aorta. RESULTS: Both Unx and Snx mice showed increased expression of markers of oxidative stress and chronic inflammation. While aortic plaque size was not different, Snx mice showed advanced plaque stages when compared to Unx mice. Darbepoetin treatment elevated hematocrit and lowered Nitrotyrosin as one marker of oxidative stress, inflammation in heart and aorta, plaque stage and in the high dose even plaque cholesterol content. In contrast, there was no influence of Darbepoetin on aortic plaque size; high dose Darbepoetin treatment resulted in elevated renal serum parameters. CONCLUSION: Darbepoetin showed some protective cardiovascular effects irrespective of renal function, i.e. it improved plaque structure and reduced some signs of oxidative stress and chronic inflammation without affecting plaque size. Nevertheless, the dose dependent adverse effects must be considered as high Darbepoetin treatment

  8. ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Terasaka, Naoki; Miyazaki, Atsuhiro; Kasanuki, Naomi; Ito, Kayoko; Ubukata, Naoko; Koieyama, Tadashi; Kitayama, Ken; Tanimoto, Tatsuo; Maeda, Naoyuki; Inaba, Toshimori

    2007-02-01

    The objective of the present study was to determine whether a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, pactimibe sulfate (CS-505), could reduce atherosclerotic lesions beyond and independent of the reduction achieved by cholesterol lowering alone from two different types of lesions. (1) Early lesion model. Twelve-week-old apolipoprotein E (apoE)(-/-) mice were treated with 0.03 or 0.1% (w/w) CS-505, 0.1 or 0.3% avasimibe (CI-1011), or 3% cholestyramine for 12 weeks. Each treatment significantly reduced plasma cholesterol by a similar degree (43-48%). The antiatherosclerotic activity of 0.1% CS-505, however, was more efficacious than the effects of the other treatments (90% versus 40-50%). (2) Advanced lesion model. Twenty-four-week-old apoE(-/-) mice were treated with 0.03 or 0.1% CS-505 or 0.1% CI-1011 for 12 weeks. CS-505 at 0.1% revealed enhanced lesion reduction compared with 0.1% CI-1011 (77% versus 54%), whereas the plasma cholesterol-lowering effect of 0.1% CS-505 was almost the same as that of 0.1% CI-1011. Furthermore, immunohistochemical analysis demonstrated that CS-505 significantly reduced the number of macrophages and expression of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13. These data indicate that CS-505 can reduce and stabilize atherosclerotic lesions. This antiatherosclerotic activity is exerted via both cholesterol lowering and direct ACAT inhibition in plaque macrophages.

  9. Multiplex coherent anti-stokes Raman spectroscopy images intact atheromatous lesions and concomitantly identifies distinct chemical profiles of atherosclerotic lipids.

    Science.gov (United States)

    Kim, Se-Hwa; Lee, Eun-Soo; Lee, Jae Yong; Lee, Eun Seong; Lee, Bok-Soo; Park, Jeong Euy; Moon, Dae Won

    2010-04-30

    Lipids are a key component of atherogenesis. However, their physiological role on the progression of atherosclerosis including plaque vulnerability has not been clearly understood, because of the lack of appropriate tools for chemical assessment. We aimed to develop a label-free chemical imaging platform based on multiplex coherent anti-Stokes Raman scattering (CARS) for the correlative study of the morphology and chemical profile of atherosclerotic lipids. Whole aortas from atherosclerotic apolipoprotein E knock-out mice were en face examined by multiplex CARS imaging and 4 distinctive morphologies of the lipids (intra/extracellular lipid droplets and needle-/plate-shaped lipid crystals) were classified. The chemical profiles of atherosclerotic lipids depending on morphologies were firstly identified from intact atheromatous tissue by multiplex CARS. We demonstrated that needle-/plate-shaped lipid crystals in advanced plaques had undergone a phase shift to the solid state with increased protein contents, implying that lipid modification had occurred beforehand. The validity of lipid-selective multiplex CARS imaging was supported by comparative results from oil red O staining and whole-mount immunohistochemistry. By spatial CARS analysis of atherosclerosis progression, we found greater accumulation of lipid crystals in both the lesser curvature of the aortic arch and the innominate artery. Furthermore, multiplex CARS measurement successfully demonstrated the effect of a drug, statin, on atherosclerotic lipids by showing the change of their chemical profiles. Multiplex CARS imaging directly provides intact morphologies of atherosclerotic lipids with correlative chemical information, thereby suggesting its potential applications in the investigation of lipid-associated disorders and the preclinical drug screening.

  10. Folic Acid Supplementation Delays Atherosclerotic Lesion Development by Modulating MCP1 and VEGF DNA Methylation Levels In Vivo and In Vitro

    Science.gov (United States)

    Cui, Shanshan; Li, Wen; Lv, Xin; Wang, Pengyan; Gao, Yuxia; Huang, Guowei

    2017-01-01

    The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells. We analyzed atherosclerotic lesion histology, folate concentration, homocysteine concentration, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and DNA methyltransferase activity, as well as monocyte chemotactic protein-1 (MCP1) and vascular endothelial growth factor (VEGF) expression and promoter methylation. Folic acid reduced atherosclerotic lesion size in ApoE knockout mice. The underlying folic acid protective mechanism appears to operate through regulating the normal homocysteine state, upregulating the SAM: SAH ratio, elevating DNA methyltransferase activity and expression, altering MCP1 and VEGF promoter methylation, and inhibiting MCP1 and VEGF expression. We conclude that folic acid supplementation effectively prevented atherosclerosis by modifying DNA methylation through the methionine cycle, improving DNA methyltransferase activity and expression, and thus changing the expression of atherosclerosis-related genes. PMID:28475147

  11. Dietary soy protein isolate ameliorates atherosclerotic lesions in apolipoprotein E-deficient mice potentially by inhibiting monocyte chemoattractant protein-1 expression.

    Science.gov (United States)

    Nagarajan, Shanmugam; Burris, Ramona L; Stewart, Bradford W; Wilkerson, James E; Badger, Thomas M

    2008-02-01

    Soy-based diets reportedly protect against the development of atherosclerosis; however, the underlying mechanism(s) for this protection remains unknown. In this report, the mechanism(s) contributing to the atheroprotective effects of a soy-based diet was addressed using the apolipoprotein E knockout (apoE-/-) mice fed soy protein isolate (SPI) associated with or without phytochemicals (SPI+ and SPI-, respectively) or casein (CAS). Reduced atherosclerotic lesions were observed in aortic sinus and enface analyses of the descending aorta in SPI+- or SPI(-)-fed apoE-/- mice compared with CAS-fed mice. SPI+-fed mice showed 20% fewer lesions compared with SPI(-)-fed mice. Plasma lipid profiles did not differ among the 3 groups, suggesting alternative mechanism(s) could have contributed to the atheroprotective effect of soy-based diets. Real-time quantitative PCR analyses of proximal aorta showed reduced expression of monocyte chemoattractant protein-1 (MCP-1), a monocyte chemokine, in mice fed both soy-based diets compared with the CAS-fed mice. These findings paralleled the reduced number of macrophages observed in the lesion site in the aorta of SPI+- or SPI(-)-fed mice compared with CAS-fed mice. In an in vitro LPS-induced inflammation model, soy isoflavones (genistein, daidzein, and equol alone or in combination) dose dependently inhibited LPS-induced MCP-1 secretion by macrophages, suggesting a role for soy isoflavones for the protective in vivo effects. Collectively, these findings suggest that the reduction in atherosclerotic lesions observed in mice fed the soy-based diet is mediated in part by inhibition of MCP-1 that could result in reduced monocyte migration, an early event during atherogenesis.

  12. Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

    Science.gov (United States)

    2014-01-01

    Background The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. Methods A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. Results After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. Conclusions The prevalence and risk of lower limb

  13. Inhibition of lipoprotein-associated phospholipase A2 ameliorates inflammation and decreases atherosclerotic plaque formation in ApoE-deficient mice.

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    Wen-yi Wang

    Full Text Available BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2 is thought to play modulatory roles in the development of atherosclerosis. Here we evaluated the effects of a specific lp-PLA2 inhibitor on atherosclerosis in ApoE-deficient mice and its associated mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: ApoE-deficient mice fed an atherogenic high-fat diet for 17 weeks were divided into two groups. One group was administered the specific lp-PLA2 inhibitor, darapladib (50 mg/kg/day; p.o. daily for 6 weeks, while the control group was administered saline. We observed no differences in body weight and serum lipids levels between the two groups at the end of the dietary period. Notably, serum lp-PLA2 activity as well as hs-CRP (C-reactive protein and IL-6 (Interleukin-6 levels were significantly reduced in the darapladib group, compared with the vehicle group, while the serum PAF (platelet-activating factor levels were similar between the two groups. Furthermore, the plaque area through the arch to the abdominal aorta was reduced in the darapladib group. Another finding of interest was that the macrophage content was decreased while collagen content was increased in atherosclerotic lesions at the aortic sinus in the darapladib group, compared with the vehicle group. Finally, quantitative RT-PCR performed to determine the expression patterns of specific inflammatory genes at atherosclerotic aortas revealed lower expression of MCP-1, VCAM-1 and TNF-α in the darapladib group. CONCLUSIONS/SIGNIFICANCE: Inhibition of lp-PLA2 by darapladib leads to attenuation of in vivo inflammation and decreased plaque formation in ApoE-deficient mice, supporting an anti-atherogenic role during the progression of atherosclerosis.

  14. Mechanism of ceroid formation in atherosclerotic plaque: in situ studies using a combination of Raman and fluorescence spectroscopy.

    Science.gov (United States)

    Haka, Abigail S; Kramer, John R; Dasari, Ramachandra R; Fitzmaurice, Maryann

    2011-01-01

    Accumulation of the lipid-protein complex ceroid is a characteristic of atherosclerotic plaque. The mechanism of ceroid formation has been extensively studied, because the complex is postulated to contribute to plaque irreversibility. Despite intensive research, ceroid deposits are defined through their fluorescence and histochemical staining properties, while their composition remains unknown. Using Raman and fluorescence spectral microscopy, we examine the composition of ceroid in situ in aorta and coronary artery plaque. The synergy of these two types of spectroscopy allows for identification of ceroid via its fluorescence signature and elucidation of its chemical composition through the acquisition of a Raman spectrum. In accordance with in vitro predictions, low density lipoprotein (LDL) appears within the deposits primarily in its peroxidized form. The main forms of modified LDL detected in both coronary artery and aortic plaques are peroxidation products from the Fenton reaction and myeloperoxidase-hypochlorite pathway. These two peroxidation products occur in similar concentrations within the deposits and represent ∼40 and 30% of the total LDL (native and peroxidized) in the aorta and coronary artery deposits, respectively. To our knowledge, this study is the first to successfully employ Raman spectroscopy to unravel a metabolic pathway involved in disease pathogenesis: the formation of ceroid in atherosclerotic plaque.

  15. Cutting-Balloon Angioplasty Versus Balloon Angioplasty as Treatment for Short Atherosclerotic Lesions in the Superficial Femoral Artery: Randomized Controlled Trial

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    Poncyljusz, Wojciech, E-mail: wponcyl@poczta.onet.pl; Falkowski, Aleksander, E-mail: bakhis@hot.pl [Pomeranian Medical University, Department of Interventional Radiology (Poland); Safranow, Krzysztof, E-mail: chrissaf@mp.pl; Rac, Monika, E-mail: carmon@pum.edu.pl [Pomeranian Medical University, Department of Biochemistry and Medical Chemistry (Poland); Zawierucha, Dariusz, E-mail: dariusz13@yahoo.com [Interventional Radiology, Sacred Heart Medical Center, River Bend (United States)

    2013-12-15

    Purpose: To evaluate the treatments of a short-segment atherosclerotic stenosis in the superficial femoral arteries with the cutting balloon angioplasty (CBA) versus conventional balloon angioplasty [percutaneous transluminal angioplasty (PTA)] in a randomized controlled trial. Material and Methods: The study group comprised 60 patients (33 men, 27 women; average age 64 years) with a short ({<=}5 cm) focal SFA de novo atherosclerotic stenosis associated with a history of intermittent claudication or rest pain. The primary end point of this study was the rate of binary restenosis in the treated segment 12 months after the intervention. All patients were evenly randomized to either the PTA or CBA treatment arms. Follow-up angiograms and ankle-brachial index (ABI) measurements were performed after 12 months. The evaluation of the restenosis rates and factors influencing its occurrence were calculated by logistic regression analysis. Results: In the intention-to-treat analysis, restenosis rates after 2-month follow-up were 9 of 30 (30 %) in the PTA group and 4 of 30 (13 %) in the CBA group (p = 0.117). In the actual treatment analysis, after exclusion of patients who required nitinol stent placement for a suboptimal result after angioplasty alone (5 patients in the PTA group and none in the CBA group), restenosis rates were 9 of 25 (36 %) and 4 of 30 (13 %), respectively (p = 0.049). In the intention-to-treat analysis there were also significant differences in ABI values between the PTA and CBA groups at 0.77 {+-} 0.11 versus 0.82 {+-} 0.12, respectively (p = 0.039), at 12 months. Conclusion: Based on the presented results of the trial, CBA seems to be a safer and more effective than PTA for treatment of short atherosclerotic lesions in the superior femoral artery.

  16. Cutting-balloon angioplasty versus balloon angioplasty as treatment for short atherosclerotic lesions in the superficial femoral artery: randomized controlled trial.

    Science.gov (United States)

    Poncyljusz, Wojciech; Falkowski, Aleksander; Safranow, Krzysztof; Rać, Monika; Zawierucha, Dariusz

    2013-12-01

    To evaluate the treatments of a short-segment atherosclerotic stenosis in the superficial femoral arteries with the cutting balloon angioplasty (CBA) versus conventional balloon angioplasty [percutaneous transluminal angioplasty (PTA)] in a randomized controlled trial. The study group comprised 60 patients (33 men, 27 women; average age 64 years) with a short (≤ 5 cm) focal SFA de novo atherosclerotic stenosis associated with a history of intermittent claudication or rest pain. The primary end point of this study was the rate of binary restenosis in the treated segment 12 months after the intervention. All patients were evenly randomized to either the PTA or CBA treatment arms. Follow-up angiograms and ankle-brachial index (ABI) measurements were performed after 12 months. The evaluation of the restenosis rates and factors influencing its occurrence were calculated by logistic regression analysis. In the intention-to-treat analysis, restenosis rates after 2-month follow-up were 9 of 30 (30 %) in the PTA group and 4 of 30 (13 %) in the CBA group (p = 0.117). In the actual treatment analysis, after exclusion of patients who required nitinol stent placement for a suboptimal result after angioplasty alone (5 patients in the PTA group and none in the CBA group), restenosis rates were 9 of 25 (36 %) and 4 of 30 (13 %), respectively (p = 0.049). In the intention-to-treat analysis there were also significant differences in ABI values between the PTA and CBA groups at 0.77 ± 0.11 versus 0.82 ± 0.12, respectively (p = 0.039), at 12 months. Based on the presented results of the trial, CBA seems to be a safer and more effective than PTA for treatment of short atherosclerotic lesions in the superior femoral artery.

  17. Adaptive lesion formation using dual mode ultrasound array system

    Science.gov (United States)

    Liu, Dalong; Casper, Andrew; Haritonova, Alyona; Ebbini, Emad S.

    2017-03-01

    We present the results from an ultrasound-guided focused ultrasound platform designed to perform real-time monitoring and control of lesion formation. Real-time signal processing of echogenicity changes during lesion formation allows for identification of signature events indicative of tissue damage. The detection of these events triggers the cessation or the reduction of the exposure (intensity and/or time) to prevent overexposure. A dual mode ultrasound array (DMUA) is used for forming single- and multiple-focus patterns in a variety of tissues. The DMUA approach allows for inherent registration between the therapeutic and imaging coordinate systems providing instantaneous, spatially-accurate feedback on lesion formation dynamics. The beamformed RF data has been shown to have high sensitivity and specificity to tissue changes during lesion formation, including in vivo. In particular, the beamformed echo data from the DMUA is very sensitive to cavitation activity in response to HIFU in a variety of modes, e.g. boiling cavitation. This form of feedback is characterized by sudden increase in echogenicity that could occur within milliseconds of the application of HIFU (see http://youtu.be/No2wh-ceTLs for an example). The real-time beamforming and signal processing allowing the adaptive control of lesion formation is enabled by a high performance GPU platform (response time within 10 msec). We present results from a series of experiments in bovine cardiac tissue demonstrating the robustness and increased speed of volumetric lesion formation for a range of clinically-relevant exposures. Gross histology demonstrate clearly that adaptive lesion formation results in tissue damage consistent with the size of the focal spot and the raster scan in 3 dimensions. In contrast, uncontrolled volumetric lesions exhibit significant pre-focal buildup due to excessive exposure from multiple full-exposure HIFU shots. Stopping or reducing the HIFU exposure upon the detection of such an

  18. A New Approach to Determining the Rates of Recruitment of Circulating Leukocytes into Tissues: Application to the Measurement of Leukocyte Recruitment into Atherosclerotic Lesions

    Science.gov (United States)

    Steinberg, Daniel; Khoo, John C.; Glass, Christopher K.; Palinski, Wulf; Almazan, Felicidad

    1997-04-01

    Recruitment of circulating monocytes into the artery wall is an important feature of early atherogenesis. In vitro studies have identified a number of adhesion molecules and chemokines that may control this process but very little work has been done to evaluate their relative importance in vivo, in part because there have been no methods available of sufficient sensitivity and reliability. This paper proposes a new approach in which advantage is taken of naturally occurring or transgenically induced mutations to ``mark'' donor cells and to follow their fate in recipient animals using highly sensitive PCR methods. The feasibility of the approach is demonstrated by preliminary studies of monocyte recruitment into atherosclerotic lesions. However, the method should in principle be applicable to the study of any of the circulating leukocytes and their rate of entry into any tissue or tissues of interest.

  19. Relative atherosclerotic plaque volume by CT coronary angiography trumps conventional stenosis assessment for identifying flow-limiting lesions.

    Science.gov (United States)

    Kato, Nahoko; Kishi, Satoru; Arbab-Zadeh, Armin; Rybicki, Frank J; Tanimoto, Shuzou; Aoki, Jiro; Watanabe, Mika; Horiuchi, Yu; Furui, Koichi; Hara, Kazuhiro; Ibukuro, Kenji; Lima, Joao A C; Tanabe, Kengo

    2017-11-01

    The new methods for diagnosing the ischemia with coronary computed tomographic angiography (CTA) as a noninvasive test have been investigated. To compare the relative plaque volume to quantitative CTA and quantitative coronary angiography (QCA) for detecting flow-limiting coronary artery stenoses. We studied 49 patients with 55 intermediate lesions (30-69% diameter stenosis) who underwent CTA, coronary angiography (CAG), and FFR. CTA and QCA measures included lesion length, percent diameter stenosis (%DS), minimal lumen diameter (MLD), target main vessel percent plaque volume (%PV), lesion %PV, target main vessel percent lumen volume (%LV), and lesion %LV. FFR ≤0.80 was considered diagnostic of a flow-limiting lesion. The area under the receiver-operating characteristic curve (AUC) was used to determine the accuracy of detecting flow-limiting lesions. We also investigated the AUC of discrimination of flow-limiting lesion according to calcium score. Eighteen of 55 lesions (32.7%) had an FFR ≤0.80. Only vessel %PV differentiated between lesions with and without flow obstruction (67.6 vs. 62.7%, p = 0.018). The AUC for vessel %PV was greatest (0.76; 95% CI 0.61-0.87). The AUC for the discrimination of the flow-limiting lesions according to low calcium score (≤400) improved to 0.82 (95% CI 0.57-0.94). In intermediate coronary artery stenoses, vessel %PV is more accurate than conventional stenosis assessment for detecting flow-limiting lesions. In low calcium score, vessel %PV is more useful for diagnosis of ischemic heart disease compared with conventional quantitative measures.

  20. Effect of Quercus infectoria and Rosa damascena on lipid profile and atherosclerotic plaque formation in rabbit model of hyperlipidemia.

    Science.gov (United States)

    Gholamhoseinian, A; Shahouzehi, B; Joukar, S; Iranpoor, M

    2012-01-01

    Hyperlipidemia is the cause of many complications in the human societies. In this study, the effect of methanol extracts of Quercus infectoria (QI) galls and Rosa damascena (RD) Mill flower were studied on lipid profile and atherosclerotic plaques formation in hyperlipidemic rabbits. Thirty-six New Zeland white rabbits randomly divided into 6 groups as control (I), hyperlipidemic (II), hyperlipidemic+QI (III), hyperlipidemic+RD (IV), +Atorvastolin (V) and hyperlipidemic+Orlistat (VI) and were fed with high fat diet (0.5% cholesterol and 16% hydrogenated vegetable oil) for 45 days. At the end of the study period, lipid profile and plaque formation were assessed. Total Cholesterol (TC), Low Density Lipoprotein (LDL) and Triglyceride (TG) levels were significantly increased in hyperlipidemic group compared with control group (p < 0.001). Methanol extract consumption of Quercus infectoria significantly decreased plasma levels of TC, TG and LDL (p < 0.001). It also decreased plaques formation in semi lunar valve and thoracic aorta. Rosa damascena mill flower methanol extract moderately decreased the levels of TC, TG, LDL and plaques formation but it was not significant. HDL levels and weight of animals did not show significant difference among groups. Based on the doses used in this study, our finding indicated that QI but no RD methanol extract has anti atherogenic and hypolipidemic activities.

  1. Eicosapentaenoic acid reduces membrane fluidity, inhibits cholesterol domain formation, and normalizes bilayer width in atherosclerotic-like model membranes.

    Science.gov (United States)

    Mason, R Preston; Jacob, Robert F; Shrivastava, Sandeep; Sherratt, Samuel C R; Chattopadhyay, Amitabha

    2016-12-01

    Cholesterol crystalline domains characterize atherosclerotic membranes, altering vascular signaling and function. Omega-3 fatty acids reduce membrane lipid peroxidation and subsequent cholesterol domain formation. We evaluated non-peroxidation-mediated effects of eicosapentaenoic acid (EPA), other TG-lowering agents, docosahexaenoic acid (DHA), and other long-chain fatty acids on membrane fluidity, bilayer width, and cholesterol domain formation in model membranes. In membranes prepared at 1.5:1 cholesterol-to-phospholipid (C/P) mole ratio (creating pre-existing domains), EPA, glycyrrhizin, arachidonic acid, and alpha linolenic acid promoted the greatest reductions in cholesterol domains (by 65.5%, 54.9%, 46.8%, and 45.2%, respectively) compared to controls; other treatments had modest effects. EPA effects on cholesterol domain formation were dose-dependent. In membranes with 1:1 C/P (predisposing domain formation), DHA, but not EPA, dose-dependently increased membrane fluidity. DHA also induced cholesterol domain formation without affecting temperature-induced changes in-bilayer unit cell periodicity relative to controls (d-space; 57Å-55Å over 15-30°C). Together, these data suggest simultaneous formation of distinct cholesterol-rich ordered domains and cholesterol-poor disordered domains in the presence of DHA. By contrast, EPA had no effect on cholesterol domain formation and produced larger d-space values relative to controls (60Å-57Å; pmembrane bilayer width, membrane fluidity, and cholesterol crystalline domain formation; suggesting omega-3 fatty acids with differing chain length or unsaturation may differentially influence membrane lipid dynamics and structural organization as a result of distinct phospholipid/sterol interactions. Copyright © 2016. Published by Elsevier B.V.

  2. Identification of periodontal pathogens in atherosclerotic vessels

    DEFF Research Database (Denmark)

    Fiehn, Nils-Erik; Larsen, Tove; Christiansen, Natalia

    2005-01-01

    Epidemiological studies have shown that periodontitis may be associated with presence of atherosclerosis. DNA from periodontal pathogens has been detected in atherosclerotic lesions, but viable oral bacteria have not yet been isolated from atherosclerotic plaques. The purpose of the present study...... was to determine if viable oral bacteria could be isolated from atherosclerotic lesions and if DNA from periodontal pathogens could be detected by use of polymerase chain reaction (PCR) techniques....

  3. Both transient and continuous corticosterone excess inhibit atherosclerotic plaque formation in APOE*3-leiden.CETP mice.

    Directory of Open Access Journals (Sweden)

    Hanna E Auvinen

    Full Text Available INTRODUCTION: The role of glucocorticoids in atherosclerosis development is not clearly established. Human studies show a clear association between glucocorticoid excess and cardiovascular disease, whereas most animal models indicate an inhibitory effect of glucocorticoids on atherosclerosis development. These animal models, however, neither reflect long-term glucocorticoid overexposure nor display human-like lipoprotein metabolism. AIM: To investigate the effects of transient and continuous glucocorticoid excess on atherosclerosis development in a mouse model with human-like lipoprotein metabolism upon feeding a Western-type diet. METHODS: Pair-housed female APOE*3-Leiden.CETP (E3L.CETP mice fed a Western-type containing 0.1% cholesterol for 20 weeks were given corticosterone (50 µg/ml for either 5 (transient group or 17 weeks (continuous group, or vehicle (control group in the drinking water. At the end of the study, atherosclerosis severity, lesion area in the aortic root, the number of monocytes adhering to the endothelial wall and macrophage content of the plaque were measured. RESULTS: Corticosterone treatment increased body weight and food intake for the duration of the treatment and increased gonadal and subcutaneous white adipose tissue weight in transient group by +35% and +31%, and in the continuous group by +140% and 110%. Strikingly, both transient and continuous corticosterone treatment decreased total atherosclerotic lesion area by -39% without lowering plasma cholesterol levels. In addition, there was a decrease of -56% in macrophage content of the plaque with continuous corticosterone treatment, and a similar trend was present with the transient treatment. CONCLUSION: Increased corticosterone exposure in mice with human-like lipoprotein metabolism has beneficial, long-lasting effects on atherosclerosis, but negatively affects body fat distribution by promoting fat accumulation in the long-term. This indicates that the increased

  4. Resolvin E1 Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation Induced Atherogenesis

    Science.gov (United States)

    Hasturk, Hatice; Abdallah, Rima; Kantarci, Alpdogan; Nguyen, Daniel; Giordano, Nicholas; Hamilton, James; Van Dyke, Thomas E.

    2015-01-01

    Objective Epidemiological and recent clinical studies implicate periodontitis as an independent risk factor for cardiovascular disease. Previously, we demonstrated that rabbits with experimental periodontitis and cholesterol diet exhibit more aortic plaque compared to diet alone. We also showed that a proresolution mediator, Resolvin E1 (RvE1), reverses the experimental periodontitis. Here, we determined whether oral/topical application of RvE1 attenuates aortic atherosclerosis induced by both diet and periodontal inflammation. Approach and Results Thirty-nine rabbits on a 13-week regimen of 0.5% cholesterol diet were included. Periodontitis was induced by P. gingivalis in 24 rabbits and 15 rabbits were placed in no-periodontitis groups. Interventions were no-treatment, vehicle, and RvE1 treatment (4μg/site or 0.4 μg/site) topically applied 3-times/ week. At 13 weeks, both periodontitis and atherosclerosis were quantified. Atherosclerotic plaques were assessed by Sudan IV staining, histology and ex vivo MRI. Serum levels of C-reactive protein (CRP) were evaluated as a measure of systemic inflammation.RvE1, used as an oral/topical agent, significantly diminished atherogenesis and prevented periodontitis (pperiodontal inflammation, oral/topical application of RvE1 resulted in significantly less arterial plaque, a lower intima/media ratio, and decreased inflammatory cell infiltration compared to no-treatment (pperiodontitis and prevents vascular inflammation and atherogenesis in the absence of periodontitis. The inhibition of vascular inflammation with endogenous mediators of resolution of inflammation provides a novel approach in the prevention of atherogenic events. PMID:25792445

  5. ACAT inhibition reduces the progression of pre-existing, advanced atherosclerotic mouse lesions without plaque or systemic toxicity

    Science.gov (United States)

    Rong, James X.; Blachford, Courtney; Feig, Jonathan E.; Bander, Ilda; Mayne, Jeffrey; Kusunoki, Jun; Miller, Christine; Davis, Matthew; Wilson, Martha; Dehn, Shirley; Thorp, Edward; Tabas, Ira; Taubman, Mark B.; Rudel, Lawrence L.; Fisher, Edward A.

    2013-01-01

    Objective Acyl-CoA:cholesterol acyltransferase (ACAT) converts cholesterol to cholesteryl esters in plaque foam cells. Complete deficiency of macrophage ACAT has been shown to increase atherosclerosis in hypercholesterolemic mice due to cytotoxicity from free cholesterol accumulation, while we previously showed that partial ACAT inhibition by Fujirebio compound F1394 decreased early atherosclerosis development. In this report, we tested F1394 effects on pre-established, advanced lesions of apoE-/- mice. Methods & Results ApoE-/- mice on Western diet for 14 weeks developed advanced plaques, and were either sacrificed (“Baseline”), or continued on Western diet without or with F1394 and sacrificed after 14 more weeks. F1394 was not associated with systemic toxicity. Compared to the baseline group, lesion size progressed in both groups; however, F1394 significantly retarded plaque progression, and reduced plaque macrophage, free and esterified cholesterol, and tissue factor contents compared to the untreated group. Apoptosis of plaque cells was not increased, consistent with the decrease in lesional free cholesterol, plaque necrosis was not increased, and efferocytosis (phagocytic clearance of apoptotic cells) was not impaired. The effects of F1394 were independent of changes in plasma cholesterol levels. Conclusions Partial ACAT inhibition by F1394 lowered plaque cholesterol content and had other antiatherogenic effects in advanced lesions in apoE-/- mice without overt systemic or plaque toxicity, suggesting the continued potential of ACAT inhibition for the clinical treatment of atherosclerosis in spite of recent trial data. PMID:23139293

  6. Factors Influencing Lesion Formation During Radiofrequency Catheter Ablation

    Directory of Open Access Journals (Sweden)

    Olaf J. Eick

    2003-07-01

    Full Text Available In radiofrequency (RF ablation, the heating of cardiac tissue is mainly resistive. RF current heats cardiac tissue and in turn the catheter electrode is being heated. Consequently, the catheter tip temperature is always lower - or ideally equal - than the superficial tissue temperature. The lesion size is influenced by many parameters such as delivered RF power, electrode length, electrode orientation, blood flow and tissue contact. This review describes the influence of these different parameters on lesion formation and provides recommendations for different catheter types on selectable parameters such as target temperatures, power limits and RF durations

  7. A new finite element method for inverse problems in structural analysis: application to atherosclerotic plaque elasticity reconstruction

    OpenAIRE

    Bouvier, Adeline,; Deleaval, Flavien; Doyley, Marvin,; Tacheau, Antoine,; Finet, Gérard; Lefloch, Simon; Cloutier, Guy; Pettigrew, Roderic; Ohayon, Jacques

    2014-01-01

    International audience; Atherosclerotic plaque rupture remains the leading cause of acute coronary syndrome (ACS), myocardial infarction and stroke (Lloyd-Jones et al. 2010). Atherosclerotic lesions develop inside the arterial wall. Vulnerable plaque (VP), which is characterised by a relatively large extracellular necrotic core and a thin fibrous cap infiltrated by macrophages, is prone to rupture (Virmani et al. 2000). The rupture of the thin-cap fibroatheroma may lead to the formation of a ...

  8. Identification of periodontal pathogens in atherosclerotic vessels

    DEFF Research Database (Denmark)

    Fiehn, Nils-Erik; Larsen, Tove; Christiansen, Natalia

    2005-01-01

    Epidemiological studies have shown that periodontitis may be associated with presence of atherosclerosis. DNA from periodontal pathogens has been detected in atherosclerotic lesions, but viable oral bacteria have not yet been isolated from atherosclerotic plaques. The purpose of the present study...

  9. Magnetic characterization of human blood in the atherosclerotic process in coronary arteries

    Energy Technology Data Exchange (ETDEWEB)

    Janus, B. [Institute of Environmental Engineering PAS, ul. SkLodowskiej-Curie 34, 41-819 Zabrze (Poland); Bucko, M.S., E-mail: michal.bucko@helsinki.f [Institute of Environmental Engineering PAS, ul. SkLodowskiej-Curie 34, 41-819 Zabrze (Poland); Division of Geophysics and Astronomy, P.O. Box 64, Gustaf Haellstroemin katu 2, 00014 University of Helsinki (Finland); Chrobak, A. [University of Silesia, Institute of Physics, ul. Uniwersytecka 4, 40-007 Katowice (Poland); Wasilewski, J. [3rd Chair and Clinical Ward of Cardiology, Medical University of Silesia, Katowice, Silesian Centre of Heart Diseases, ul. Szpitalna 2, 41-800 Zabrze (Poland); Zych, M. [Department of Pharmacognosy and Phytochemistry, Medical University of Silesia, ul. Jagiellonska 4, 41-200 Sosnowiec (Poland)

    2011-03-15

    In the last decades there has been an increasing interest in biomagnetism-a field of biophysics concerned with the magnetic properties of living organisms. Biomagnetism focuses on the measurement of magnetic properties of biological samples in the clinical environment. Progress in this field can provide new data for the understanding of the pathomechanism of atherosclerosis and support the diagnostic options for the evaluation and treatment of atherothrombotic complications. Lyophilized human blood samples from patients with atherosclerotic lesions (calcium scoring (CS) CS>0) and without atherosclerotic lesions (CS=0) were magnetically investigated. Magnetic measurements (performed in room and low temperature) indicated significant magnetic differences between these two groups of patients. Atherosclerotic blood samples are characterized by higher concentration of ferrimagnetic particles (magnetite and/or maghemite) and significant changes in the superparamagnetic behaviour. This research presents that magnetometry, in combination with medical research can lead to a better understanding of iron physiology in the atherosclerotic process. - Research Highlights: {yields}Blood samples are characterized by higher concentration of ferrimagnetic particles. {yields}Atherosclerotic blood samples consist of larger superparamagnetic clusters. {yields}Superparamagnetic particles in pathological samples are considered to be magnetite. {yields}The formation of ferrimagnetic particles is favoured in the atherosclerotic patients. {yields}Magnetite may play a role in the progression of atherosclerosis.

  10. Self-gated CINE MRI for combined contrast-enhanced imaging and wall-stiffness measurements of murine aortic atherosclerotic lesions

    NARCIS (Netherlands)

    den Adel, Brigit; van der Graaf, Linda M.; Strijkers, Gustav J.; Lamb, Hildo J.; Poelmann, Robert E.; van der Weerd, Louise

    2013-01-01

    High-resolution contrast-enhanced imaging of the murine atherosclerotic vessel wall is difficult due to unpredictable flow artifacts, motion of the thin artery wall and problems with flow suppression in the presence of a circulating contrast agent. We applied a 2D-FLASH retrospective-gated CINE MRI

  11. The Protective Effect of Apamin on LPS/Fat-Induced Atherosclerotic Mice

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    Soo-Jung Kim

    2012-01-01

    Full Text Available Apamin, a peptide component of bee venom (BV, has anti-inflammatory properties. However, the molecular mechanisms by which apamin prevents atherosclerosis are not fully understood. We examined the effect of apamin on atherosclerotic mice. Atherosclerotic mice received intraperitoneal (ip injections of lipopolysaccharide (LPS, 2 mg/kg to induce atherosclerotic change and were fed an atherogenic diet for 12 weeks. Apamin (0.05 mg/kg was administered by ip injection. LPS-induced THP-1-derived macrophage inflammation treated with apamin reduced expression of tumor necrosis factor (TNF-α, vascular cell adhesion molecule (VCAM-1, and intracellular cell adhesion molecule (ICAM-1, as well as the nuclear factor kappa B (NF-κB signaling pathway. Apamin decreased the formation of atherosclerotic lesions as assessed by hematoxylin and elastic staining. Treatment with apamin reduced lipids, Ca2+ levels, and TNF-α in the serum from atherosclerotic mice. Further, apamin significantly attenuated expression of VCAM-1, ICAM-1, TGF-β1, and fibronectin in the descending aorta from atherosclerotic mice. These results indicate that apamin plays an important role in monocyte/macrophage inflammatory processing and may be of potential value for preventing atherosclerosis.

  12. Vaporization of atherosclerotic plaques by spark erosion

    OpenAIRE

    Slager, Cornelis J.; Essed, Catharina E.; Schuurbiers, Johan C.H.; Bom, Nicolaas; Serruys, Patrick W.; Meester, Geert T.

    1985-01-01

    textabstractAn alternative to the laser irradiation of atherosclerotic lesions has been developed. A pulsed electrocardiogram R wave-triggered electrical spark erosion technique is described. Controlled vaporization of fibrous and lipid plaques with minimal thermal side effects was achieved and documented histologically in vitro from 30 atherosclerotic segments of six human aortic autopsy specimens. Craters with a constant area and a depth that varied according to the duration of application ...

  13. Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae

    NARCIS (Netherlands)

    de Boer, O. J.; van der Wal, A. C.; Houtkamp, M. A.; Ossewaarde, J. M.; Teeling, P.; Becker, A. E.

    2000-01-01

    OBJECTIVE: Atherosclerotic lesions are characterized by an immune mediated chronic inflammation. Seroepidemiological studies support a relationship between atherosclerotic disease and infection with C. pneumoniae; an association further endorsed by immunocytochemical and DNA directed studies.

  14. Myeloid protein tyrosine phosphatase 1B (PTP1B deficiency protects against atherosclerotic plaque formation in the ApoE−/− mouse model of atherosclerosis with alterations in IL10/AMPKα pathway

    Directory of Open Access Journals (Sweden)

    D. Thompson

    2017-08-01

    Conclusions: Here we demonstrate that inhibiting the activity of PTP1B specifically in myeloid lineage cells protects against atherosclerotic plaque formation, under atherogenic conditions, in an ApoE−/− mouse model of atherosclerosis. Our findings suggest for the first time that macrophage PTP1B targeting could be a therapeutic target for atherosclerosis treatment and reduction of CVD risk.

  15. Progression of White Matter Lesion Volume and Health-Related Quality of Life in Patients with Symptomatic Atherosclerotic Disease: The SMART-MR Study

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    Anne M. Grool

    2011-01-01

    Results. Physical functioning (baseline: 44, 10th–90th percentile 29–55 improved, whereas mental functioning (baseline: 51, 10th–90th percentile 32–60 declined during followup. WML progression (highest quartile versus rest contributed to a stronger decline in mental functioning (B=−1.76, 95% CI −3.11 to −0.42, but did not influence changes in physical functioning. Conclusions. Progression of WML volume contributes to a decline in mental functioning in patients with symptomatic atherosclerotic disease.

  16. [Benign fibro-osseous lesions of the craniofacial complex with aneurysmal bone cyst formation].

    Science.gov (United States)

    Geraldo, Ana Filipa; Mendes Dos Santos, Carolina; Tavares, Joana; Fernandes Sousa, Rita; Campos, Alexandre; Farias, João Paulo; Pimentel, José; Guedes Campos, Jorge

    2012-01-01

    Aneurysmal bone cyst are controversial osteolytic benign expansive lesions which occur more frequently in the metaphysis of long bones and spine. They are classified as primary or secondary lesions depending on the presence or absence of an associated bone pathology. The engraftment of aneurysmal bone cyst onto benign fibro-osseous lesions is established. However, in the craniofacial complex this combined lesion is rare.The authors present two histologically proven uncommon cases of benign fibro-osseous lesions (fibrous dysplasia and juvenile psammomatoid ossifying fibroma) with aneurysmal bone cyst formation, emphasizing the imaging characteristics of this hybrid entities.

  17. Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease.

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    Juan A Rodriguez-Feo

    Full Text Available Caveolin-1 (Cav-1 is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice. This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target

  18. Estudo histopatológico de lesões ateroscleróticas em suínos de raça Alentejana Histopathological study of atherosclerotic lesions in Alentejano pigs

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    A. Ramos

    2007-01-01

    Full Text Available Neste trabalho experimental procedeu-se à medição da espessura e à caracterização histológica de lesões ateroscleróticas, em suínos de raça Alentejana, procurando-se estabelecer uma relação entre estas e os valores dos parâmetros sanguíneos associados ao desenvolvimento deste processo patológico. As concentrações plasmáticas de triacilgliceróis, fosfolípidos, colesterol total, colesterol livre, LDLc e HDLc foram determinadas por métodos enzimáticos. Foram também feitas análises histopatológicas a amostras da artéria coronária esquerda. Os animais foram divididos em 2 grupos de 6 indivíduos cada: Grupo I, com elevada colesterolémia (4,25 mmol/L e Grupo II, com níveis normais (2,53 mmol/L. Os valores do ganho médio diário (GMD dos dois grupos foram semelhantes. Os animais do Grupo I apresentaram valores significativamente mais elevados (P=0,001 para: colesterol total, colesterol livre, colesterol esterificado e LDLc. A área de lesão foi significativamente superior (P=0,05 no Grupo I. Verificou-se uma relação linear entre a área de lesão (fases iniciais do tipo I e II e os teores plasmáticos de colesterol total, de LDLc e de colesterol livre, o que sugere a influência destes parâmetros na dimensão da área de lesão. Os resultados deste trabalho sugerem que os suínos de raça Alentejana podem desenvolver lesões ateroscleróticas ao longo do seu ciclo de vida, tal como o observado em humanos e outras raças de suínos. Estas lesões estão associadas a hipercolesterolemia que poderão ser devidas a mutações genéticas em apolipoproteínas, sistemas enzimáticos ou receptores. São necessários estudos futuros, quer a nível histológico quer a nível de biologia molecular, para um maior aprofundamento do conhecimento das lesões ateroscleróticas em suínos de raça Alentejana.The present study aimed to assess the histopathological characterization of atherosclerotic lesions in Alentejano pigs, and to

  19. Angiogenesis in the atherosclerotic plaque

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    Caroline Camaré

    2017-08-01

    Full Text Available Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.

  20. Effect of hydroalcoholic extract of Hypericum perforatum on selected traditional and novel biochemical factors of cardiovascular diseases and atherosclerotic lesions in hypercholesterolemic rabbits: A comparison between the extract and lovastatin

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    Sedigheh Asgary

    2012-01-01

    Full Text Available Context: Evidence suggests that diets with high contents of cholesterol will increase serum lipoproteins and apolipoproteins, thereby increase risk of atherosclerosis. According to literature, some plants show hypolipidemic, hypocholestrolemic, and antiatherosclerotic activities. Aims: In this study, antiatherosclerotic effect of Hypericum perforatum hydroalcoholic extract on hypercholesterolemic rabbits was compared with that of lovastatin. Materials and Methods: Twenty five mature male New Zealand rabbits were randomly divided into five groups of five and were fed for 60 days as follows: Standard diet (GroupI, standard diet and hydroalcoholic extract of Hypericum perforatum (150 mg/kg daily(GroupII, standard diet, hydroalcoholic extract of Hypericum perforatum (150 mg/ kg daily and cholesterol (1% of food content (Group III, standard diet and cholesterol (1% of food content(GroupIV, and finally standard diet, lovastatin (10 mg/kg, and cholesterol (1% of foodcontent (GroupV. Results: Hypericum perforatum extract significantly decreased the levels of apolipoprotein B(apoB, apolipoprotein B/apolipoprotein A (apoB/apoA, triglyceride, cholesterol, low density lipoprotein cholesterol, oxidized LDL, malondialdehyde, and C-reactive protein (CRP as well as atherosclerosis index, and increased high density lipoprotein and apoA in rabbits of Group III compared to the rabbits of Group IV. The effect of Hypericum perforatum extract in decreasing the level of some biochemical factors like apoB, apoB/apoA, and CRP was meaningfully more than that of lovastatin. Histopathological findings confirmed that hydroalcoholic extract of Hypericum perforatum restricted the atherosclerotic lesions. Conclusions: This study indicates that hydroalcoholic extract of Hypericum perforatum possesses hypolipidemic and anti-atherosclerotic effects and could be beneficial in the management of hyperlipidemia and atherosclerosis.

  1. Stress analysis of fracture of atherosclerotic plaques: crack propagation modeling.

    Science.gov (United States)

    Rezvani-Sharif, Alireza; Tafazzoli-Shadpour, Mohammad; Kazemi-Saleh, Davood; Sotoudeh-Anvari, Maryam

    2017-08-01

    Traditionally, the degree of luminal obstruction has been used to assess the vulnerability of atherosclerotic plaques. However, recent studies have revealed that other factors such as plaque morphology, material properties of lesion components and blood pressure may contribute to the fracture of atherosclerotic plaques. The aim of this study was to investigate the mechanism of fracture of atherosclerotic plaques based on the mechanical stress distribution and fatigue analysis by means of numerical simulation. Realistic models of type V plaques were reconstructed based on histological images. Finite element method was used to determine mechanical stress distribution within the plaque. Assuming that crack propagation initiated at the sites of stress concentration, crack propagation due to pulsatile blood pressure was modeled. Results showed that crack propagation considerably changed the stress field within the plaque and in some cases led to initiation of secondary cracks. The lipid pool stiffness affected the location of crack formation and the rate and direction of crack propagation. Moreover, increasing the mean or pulse pressure decreased the number of cycles to rupture. It is suggested that crack propagation analysis can lead to a better recognition of factors involved in plaque rupture and more accurate determination of vulnerable plaques.

  2. Salusins: Potential Use as a Biomarker for Atherosclerotic Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Kengo Sato

    2013-01-01

    Full Text Available Human salusin-α and salusin-β are related peptides produced from prosalusin. Bolus injection of salusin-β into rats induces more profound hypotension and bradycardia than salusin-α. Central administration of salusin-β increases blood pressure via release of norepinephrine and arginine-vasopressin. Circulating levels of salusin-α and salusin-β are lower in patients with essential hypertension. Salusin-β exerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs and fibroblasts than salusin-α. Salusin-β accelerates inflammatory responses in human endothelial cells and monocyte-endothelial adhesion. Human macrophage foam cell formation is stimulated by salusin-β but suppressed by salusin-α. Chronic salusin-β infusion into apolipoprotein E-deficient mice enhances atherosclerotic lesions; salusin-α infusion reduces lesions. Salusin-β is expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-α and salusin-β immunoreactivity have been detected in human coronary atherosclerotic plaques, with dominance of salusin-β in macrophage foam cells, VSMCs, and fibroblasts. Circulating salusin-β levels increase and salusin-α levels decrease in patients with coronary artery disease. These findings suggest that salusin-β and salusin-α may contribute to proatherogenesis and antiatherogenesis, respectively. Increased salusin-β and/or decreased salusin-α levels in circulating blood and vascular tissue are closely linked with atherosclerosis. Salusin-α and salusin-β could be candidate biomarkers and therapeutic targets for atherosclerotic cardiovascular diseases.

  3. [On the mechanism of the formation of traumatic lesions of the larynx: observations on three cases (author's transl)].

    Science.gov (United States)

    Masotti, G; Valli, P

    1976-01-01

    The authors, having drawn attention to the rarity of traumatic lesions of the larynx, illustrate three cases mentioning in particular the disproportion between the external and internal lesions, (as has already been pointed out by other authors), and the mechanism of the formation of such lesions. This, in particular, on the strenght of interpretations of slight cutaneous lesions.

  4. Modeling HMI measurement of HIFU lesion formation with temperature-dependent tissue properties

    Science.gov (United States)

    Draudt, Andrew B.; Cleveland, Robin O.

    2012-10-01

    Monitoring tissue stiffness changes during HIFU lesion formation may be possible by measuring the motion induced by the amplitude-modulation of the HIFU beam. As a lesion forms both the stiffness and the acoustic absorption increase. Nominally the increase in tissue stiffness results in less motion, whilst the increase in acoustic absorption results in more forcing and hence more displacement. To investigate whether these two effects cancel out, a finite element model was developed which allowed the temperature dependence of absorption and shear modulus to affect the simultaneous evolution of the acoustic, thermal, and displacement fields. For the displacement the tissue surface was assumed to be in contact with water and was therefore free to move. Measurements of bovine liver and chicken breast indicated that after lesion formation attenuation increased by 200-500% and stiffness increased by 230% for chicken, and by a factor of 40 for liver. The model results showed that, until the lesion grew well outside of the focal region, the increase in attenuation dominated and the displacement increased by 30% after lesion formation. Experimental measurement of displacement vs depth in excised bovine liver and chicken breast subject to 1.1 MHz HIFU were consistent with the predictions of the model. However, sample-to-sample variation in displacement was greater than the predicted change due to lesion formation, suggesting that changes may be difficult to detect in practice. [Work supported in part by NSF through award EEC-9986821

  5. Vaporization of atherosclerotic plaques by spark erosion

    NARCIS (Netherlands)

    C.J. Slager (Cornelis); C.E. Essed; J.C.H. Schuurbiers (Johan); N. Bom (Klaas); P.W.J.C. Serruys (Patrick); G.T. Meester (Geert)

    1985-01-01

    textabstractAn alternative to the laser irradiation of atherosclerotic lesions has been developed. A pulsed electrocardiogram R wave-triggered electrical spark erosion technique is described. Controlled vaporization of fibrous and lipid plaques with minimal thermal side effects was achieved and

  6. How to manage hypertension with atherosclerotic renal artery stenosis?

    Science.gov (United States)

    Ricco, Jean-Baptiste; Belmonte, Romain; Illuminati, Guilio; Barral, Xavier; Schneider, Fabrice; Chavent, Bertrand

    2017-04-01

    The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

  7. [Mechanistic modelling allows to assess pathways of DNA lesion interactions underlying chromosome aberration formation].

    Science.gov (United States)

    Eĭdel'man, Iu A; Slanina, S V; Sal'nikov, I V; Andreev, S G

    2012-12-01

    The knowledge of radiation-induced chromosomal aberration (CA) mechanisms is required in many fields of radiation genetics, radiation biology, biodosimetry, etc. However, these mechanisms are yet to be quantitatively characterised. One of the reasons is that the relationships between primary lesions of DNA/chromatin/chromosomes and dose-response curves for CA are unknown because the pathways of lesion interactions in an interphase nucleus are currently inaccessible for direct experimental observation. This article aims for the comparative analysis of two principally different scenarios of formation of simple and complex interchromosomal exchange aberrations: by lesion interactions at chromosome territories' surface vs. in the whole space of the nucleus. The analysis was based on quantitative mechanistic modelling of different levels of structures and processes involved in CA formation: chromosome structure in an interphase nucleus, induction, repair and interactions of DNA lesions. It was shown that the restricted diffusion of chromosomal loci, predicted by computational modelling of chromosome organization, results in lesion interactions in the whole space of the nucleus being impossible. At the same time, predicted features of subchromosomal dynamics agrees well with in vivo observations and does not contradict the mechanism of CA formation at the surface of chromosome territories. On the other hand, the "surface mechanism" of CA formation, despite having certain qualities, proved to be insufficient to explain high frequency of complex exchange aberrations observed by mFISH technique. The alternative mechanism, CA formation on nuclear centres is expected to be sufficient to explain frequent complex exchanges.

  8. Anatomical and Physiological Changes after Paclitaxel-Coated Balloon for Atherosclerotic De Novo Coronary Lesions: Serial IVUS-VH and FFR Study.

    Directory of Open Access Journals (Sweden)

    Soe Hee Ann

    Full Text Available To assess the serial changes of de novo coronary lesions treated with paclitaxel-coated balloon (PCB using intravascular ultrasound virtual histology (IVUS-VH and fractional flow reserve (FFR.This prospective observational study enrolled 27 patients with coronary artery disease treated with PCB who underwent coronary angiography, IVUS-VH and FFR before, immediately after intervention and at 9 months. 28 de novo lesions were successfully treated with PCB. Angiographic late luminal loss was 0.02 ± 0.27 mm. Mean vessel and lumen areas showed increase at 9 months (12.0 ± 3.5 mm(2 to 13.2 ± 3.9 mm(2, p <0.001; and 5.4 ± 1.2 mm(2 to 6.5 ± 1.8 mm(2, p <0.001, respectively. Although mean plaque area was unchanged (6.6 ± 2.6 mm2 to 6.6 ± 2.4 mm(2, p = 0.269, percent atheroma volume decreased significantly (53.4 ± 7.9% to 49.5 ± 6.4%, p = 0.002. The proportion of plaque compositions including fibrous, fibrofatty, dense calcium and necrotic core by IVUS-VH was unchanged at 9 months. The FFR of the treated lesion was 0.71 ± 0.13 pre-procedure, 0.87 ± 0.06 post-procedure and 0.84 ± 0.06 at follow-up.De novo coronary lesions treated with PCB showed persistent anatomical and physiological patency with plaque redistribution and vessel remodeling without chronic elastic recoil or plaque compositional change during follow-up.

  9. Stepwise Excavation Allows Apexogenesis in Permanent Molars with Deep Carious Lesions and Incomplete Root Formation.

    Science.gov (United States)

    Hernandéz-Gatón, Patrícia; Serrano, César Ruiz; Nelson Filho, Paulo; De Castañeda, Esther Ruiz; Lucisano, Marília P; Silva, Raquel A B da; Silva, Léa A B da

    2015-01-01

    This study evaluated the stepwise excavation technique in 138 permanent molars with deep carious lesions and incomplete root formation within a 24-month clinical and radiographic follow-up period. In 96.7% of the cases, success was observed (no pain, integrity of restoration margins, absence of radiographic alterations and apexogenesis). The cases of failure (3.3%) were due to the loss of the temporary restoration. In conclusion, the stepwise excavation is a promising technique for permanent teeth with deep carious lesions and incomplete root formation as a minimally invasive approach because it allows the preservation of pulp vitality and occurrence of apexogenesis. © 2015 S. Karger AG, Basel.

  10. Open-irrigated laser catheter ablation: influence of catheter-tissue contact force on lesion formation.

    Science.gov (United States)

    Sagerer-Gerhardt, Michaela; Weber, Helmut P

    2015-03-01

    Catheter-tissue contact force (CF) is a major determinant for radiofrequency (RF) ablation lesion size and quality. We sought to test the influence of catheter CF on lesion formation by using an open-irrigated electrode-laser mapping and ablation (ELMA) catheter. With the ELMA catheter in a stable vertical position, continuous wave 1064 nm laser impacts at 15 W (9.5 W/mm(2)), 30 s (285 J/mm(2)), irrigation flow 30 mL/min, were aimed at the endocardial surface of bovine myocardium in heparinized stagnant blood (ACT >350 s) at room temperature (18 °C). Lesions were produced with CFs of 100 g, 10 g, in contact but without pressure, with the catheter tip 2.0 mm, and 5.0 mm away (n = 10, each). Lesions were evaluated morphometrically and were compared by the unpaired t tests. There were no significant differences between volumes of lesions achieved with catheter-tissue CF of 100 g, 10 g, and in contact without pressure: 297 ± 56.0 vs. 300 ± 39 vs. 320 ± 24, respectively (p > 0.05). However, volumes of lesions produced at a distance of 2 mm (95 ± 14 mm(3)) were significantly smaller (p laser ablation lesion size and quality. Maximum sizes of lesions can be achieved with the catheter in intimate endocardial contact without pressure. However, lesions can be produced also at a catheter-tissue distance of 2.0 mm. Noticeably, there is no thrombus formation during laser application with the free floating ELMA catheter in the stagnant blood.

  11. The evaluation of primary stenting of sirolimus-eluting versus bare-metal stents in the treatment of atherosclerotic lesions of crural arteries

    Energy Technology Data Exchange (ETDEWEB)

    Falkowski, Aleksander; Wilk, Grazyna [Pomeranian Medical University of Szczecin, Departament of General and Dental Diagnostic Imaging, Szczecin (Poland); Poncyljusz, Wojciech [Pomeranian Medical University of Szczecin, Departament of Diagnostic Imaging and Interventional Radiology, Szczecin (Poland); Szczerbo-Trojanowska, Malgorzata [Medical University of Lublin, Department of Interventional Radiology and Neuroradiology, Lublin (Poland)

    2009-04-15

    A comparison was made of sirolimus-eluting stents and bare stents as an effective means of treatment of stenosis in crural arteries. Patients were randomly divided into two groups: (1) patients treated with sirolimus-eluting stents and (2) patients treated with bare stents. Each group consisted of 25 patients, and every patient had one stent implanted. All patients showed symptoms of ischemia of the peripheral arteries, classified according to the Rutherford scale into categories 3, 4, and 5. All patients were examined 24 h before and 24 h and 6 months after the intervention. The results were analyzed according to clinical, hemodynamic, and angiographic criteria. Technically, the procedure was successful in 100% of cases, and both groups presented an equal improvement in clinical and hemodynamic parameters. The follow-up angiographic examination demonstrated a significantly lower rate of restenosis among the sirolimus-eluting stent group (4, 16%) versus the bare stent group (19, 76%) (p < 0.001), with lower target lesion revascularization in 3 (12%) versus 14 (56%) (p < 0.05), respectively. Quantitative angiography demonstrated that all variables used to assess restenosis were superior for sirolimus-eluting stents 6 months after intervention: late lumen loss 0.46 {+-} 0.72 versus 1.70 {+-} 0.94 (p < 0.001) and minimal lumen diameter 2.25 {+-} 0.82 versus 0.99 {+-} 1.08 (p < 0.001). Results of this study reveal that the use of sirolimus-eluting stents decreases the risk of restenosis in comparison to standard stents. (orig.)

  12. The evaluation of primary stenting of sirolimus-eluting versus bare-metal stents in the treatment of atherosclerotic lesions of crural arteries.

    Science.gov (United States)

    Falkowski, Aleksander; Poncyljusz, Wojciech; Wilk, Grazyna; Szczerbo-Trojanowska, Małgorzata

    2009-04-01

    A comparison was made of sirolimus-eluting stents and bare stents as an effective means of treatment of stenosis in crural arteries. Patients were randomly divided into two groups: (1) patients treated with sirolimus-eluting stents and (2) patients treated with bare stents. Each group consisted of 25 patients, and every patient had one stent implanted. All patients showed symptoms of ischemia of the peripheral arteries, classified according to the Rutherford scale into categories 3, 4, and 5. All patients were examined 24 h before and 24 h and 6 months after the intervention. The results were analyzed according to clinical, hemodynamic, and angiographic criteria. Technically, the procedure was successful in 100% of cases, and both groups presented an equal improvement in clinical and hemodynamic parameters. The follow-up angiographic examination demonstrated a significantly lower rate of restenosis among the sirolimus-eluting stent group (4, 16%) versus the bare stent group (19, 76%) (p < 0.001), with lower target lesion revascularization in 3 (12%) versus 14 (56%) (p < 0.05), respectively. Quantitative angiography demonstrated that all variables used to assess restenosis were superior for sirolimus-eluting stents 6 months after intervention: late lumen loss 0.46 +/- 0.72 versus 1.70 +/- 0.94 (p < 0.001) and minimal lumen diameter 2.25 +/- 0.82 versus 0.99 +/- 1.08 (p < 0.001). Results of this study reveal that the use of sirolimus-eluting stents decreases the risk of restenosis in comparison to standard stents.

  13. Interferon-microRNA signalling drives liver precancerous lesion formation and hepatocarcinogenesis.

    Science.gov (United States)

    Yang, Yingcheng; Lin, Ximeng; Lu, Xinyuan; Luo, Guijuan; Zeng, Tao; Tang, Jing; Jiang, Feng; Li, Liang; Cui, Xiuliang; Huang, Wentao; Hou, Guojun; Chen, Xin; Ouyang, Qing; Tang, Shanhua; Sun, Huanlin; Chen, Luonan; Gonzalez, Frank J; Wu, Mengchao; Cong, Wenming; Chen, Lei; Wang, Hongyang

    2016-07-01

    Precancerous lesion, a well-established histopathologically premalignant tissue with the highest risk for tumourigenesis, develops preferentially from activation of DNA damage checkpoint and persistent inflammation. However, little is known about the mechanisms by which precancerous lesions are initiated and their physiological significance. Laser capture microdissection was used to acquire matched normal liver, precancerous lesion and tumour tissues. miR-484(-/-), Ifnar1(-/-) and Tgfbr2(△hep) mice were employed to determine the critical role of the interferon (IFN)-microRNA pathway in precancerous lesion formation and tumourigenesis. RNA immunoprecipitation (RIP), pull-down and chromatin immunoprecipitation (ChIP) assays were applied to explore the underlying mechanisms. miR-484 is highly expressed in over 88% liver samples clinically. DEN-induced precancerous lesions and hepatocellular carcinoma were dramatically impaired in miR-484(-/-) mice. Mechanistically, ectopic expression of miR-484 initiates tumourigenesis and cell malignant transformation through synergistic activation of the transforming growth factor-β/Gli and nuclear factor-κB/type I IFN pathways. Specific acetylation of H3K27 is indispensable for basal IFN-induced continuous transcription of miR-484 and cell transformation. Convincingly, formation of precancerous lesions were significantly attenuated in both Tgfbr2(△hep) and Ifnar1(-/-) mice. These findings demonstrate a new protumourigenic axis involving type I IFN-microRNA signalling, providing a potential therapeutic strategy to manipulate or reverse liver precancerous lesions and tumourigenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Experimental high-intensity focused ultrasound lesion formation in cardiac tissue

    Science.gov (United States)

    Muratore, Robert; Kalisz, Andrew; Lee, Paul; Lizzi, Frederic; Fujikura, Kana; Otsuka, Ryo; Homma, Shunichi

    2004-05-01

    High-intensity focused ultrasound (HIFU) (4.5-7.5 MHz) was used to form lesions in cardiac tissue, with an ultimate objective of treating conditions such as hypertrophic cardiomyopathy and ventricular tachycardia. Ultrasound attenuation coefficients were experimentally determined in vitro for calf myocardial tissue, both muscle and pericardial fat. These coefficients were employed in computational models of linear beam propagation, tissue heating profiles and thermal lesion formation for a variety of focused transducers. Modeling was performed for continuous and pulsed exposures. These models suggested initial power levels and exposure durations for in vitro experiments on calf ventricles and septa and ex vivo experiments on canine whole hearts. Repeatability of lesion size and placement was studied as power and exposure parameters varied around the initial values. With these experimental results, power and exposure parameters were selected to create lesions in vivo in canine ventricles and septa in open-chest, anesthetized dogs. Pulsed exposures were synchronized to cardiac and respiration cycles to ensure accurate placement of the lesions. These initial in vivo experiments showed that HIFU treatments in the beating heart are feasible; they also identified refinements that are now being implemented for better control of lesion size and placement. [Work supported by NCI and NHLBI Grant 5R01 CA84588.

  15. Effects of Triple Cryoenergy Application on Lesion Formation and Coronary Arteries in the Developing Myocardium.

    Science.gov (United States)

    Krause, Ulrich; Abreu da Cunha, Filipe D; Backhoff, David; Jacobshagen, Claudius; Klehs, Sophia; Schneider, Heike E; Paul, Thomas

    2017-04-01

    To improve long-term outcome after cryoablation of substrates of supraventricular tachycardia, application of two and three consecutive freeze-thaw cycles has been performed. The effect of triple freeze-thaw cycles on lesion formation within developing myocardium and coronary arteries, however, has not been studied yet. In eight piglets (mean age 15 weeks, weight 15-20 kg), 30 cryolesions (three consecutive freeze-thaw cycles) were applied to the atrial aspect of both AV valve annuli (n = 18) as well as to ventricular myocardium below the valves (n = 12). Coronary angiography was performed before and after cryoenergy application. The animals were reevaluated by coronary angiography and intracoronary ultrasound (ICUS) after 48 h. All hearts were removed for histological examination of the lesions subsequently. After staining (hematoxylin-eosin, desmin immunohistochemistry), lesions was measured by planimetry with a digital virtual miscroscope analysis system and volumes of the cryolesions were calculated. Mean atrial lesion volume was 190.68 ± 167.53 mm(3) (n = 18), and mean ventricular lesion volume was 184.34 ± 107.42 mm(3) (n = 12). Compared with previously reported data on lesion volumes after single and double freeze-thaw cycles, lesions were significantly larger. Coronary arteries were unaffected on coronary angiography as well as on ICUS. No affection of coronary arteries was found on histological examination. Application of three consecutive freeze-thaw cycles resulted in increased lesion volume compared with single and double freeze-thaw cycles. No affection of the coronary arteries was evident. To evaluate the clinical benefit and safety of triple cryoenergy application for catheter ablation, prospective randomized trials are required.

  16. Evaluation of the incidence of periodontitis-associated bacteria in the atherosclerotic plaque of coronary blood vessels.

    Science.gov (United States)

    Zaremba, Maciej; Górska, Renata; Suwalski, Piotr; Kowalski, Jan

    2007-02-01

    Unstable atherosclerotic plaque is a dangerous clinical condition, possibly leading to acute coronary deficiency resulting in cardiac infarction. Questions about the role of inflammatory factors in the formation of pathological lesions in the endothelium of coronary vessels have often been raised. This condition may be caused by bacteria that are able to initiate clot formation in a blood vessel, destabilizing an atherosclerotic plaque that is already present. The sources of these pathogens are chronic inflammatory processes occurring in the host, including periodontal disease, which is one of the most frequent conditions. The aim of this study was to evaluate the incidence of selected anaerobic bacteria in subgingival and atherosclerotic plaque in patients treated surgically because of coronary vessel obliteration. The study was performed on 20 individuals with chronic periodontitis. Subgingival plaque was collected from periodontal pockets >5 mm. DNA testing was used to identify eight pathogens responsible for periodontal tissue destruction. Material from atherosclerotic plaques was collected from the same patients during bypass surgery, and DNA testing by the same method was performed. In 13 of 20 patients, the pathogens most frequently found in severe chronic periodontitis were also found in coronary vessels. In 10 cases, those species of bacteria were also present in atherosclerotic plaque. The most frequently identified bacteria were Porphyromonas gingivalis and Treponema denticola. In patients with the severe form of chronic periodontitis, it seems that clinical attachment loss is not associated with bacterial permeability into coronary vessels. What is important is the presence of an active inflammatory process expressed by a significantly higher bleeding index in those patients in whom the examined bacterial species were found in atherosclerotic plaque.

  17. ASCIZ regulates lesion-specific Rad51 focus formation and apoptosis after methylating DNA damage.

    Science.gov (United States)

    McNees, Carolyn J; Conlan, Lindus A; Tenis, Nora; Heierhorst, Jörg

    2005-07-06

    Nuclear Rad51 focus formation is required for homology-directed repair of DNA double-strand breaks (DSBs), but its regulation in response to non-DSB lesions is poorly understood. Here we report a novel human SQ/TQ cluster domain-containing protein termed ASCIZ that forms Rad51-containing foci in response to base-modifying DNA methylating agents but not in response to DSB-inducing agents. ASCIZ foci seem to form prior to Rad51 recruitment, and an ASCIZ core domain can concentrate Rad51 in focus-like structures independently of DNA damage. ASCIZ depletion dramatically increases apoptosis after methylating DNA damage and impairs Rad51 focus formation in response to methylating agents but not after ionizing radiation. ASCIZ focus formation and increased apoptosis in ASCIZ-depleted cells depend on the mismatch repair protein MLH1. Interestingly, ASCIZ foci form efficiently during G1 phase, when sister chromatids are unavailable as recombination templates. We propose that ASCIZ acts as a lesion-specific focus scaffold in a Rad51-dependent pathway that resolves cytotoxic repair intermediates, most likely single-stranded DNA gaps, resulting from MLH1-dependent processing of base lesions.

  18. Research Progress on the Risk Factors and Outcomes of Human Carotid Atherosclerotic Plaques.

    Science.gov (United States)

    Xiong, Xiang-Dong; Xiong, Wei-Dong; Xiong, Shang-Shen; Chen, Gui-Hai

    2017-03-20

    Atherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention. We searched the PubMed database for recently published research articles up to June 2016, with the key words of "risk factors", "outcomes", "blood components", "molecular mechanisms", "cellular mechanisms", and "human carotid atherosclerotic plaques". The articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected. This review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque. Carotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis.

  19. Anti-atherosclerotic effect of traditional fermented cheese whey in atherosclerotic rabbits and identification of probiotics.

    Science.gov (United States)

    Nabi, Xin-Hua; Ma, Chun-Yan; Manaer, Tabusi; Heizati, Mulalibieke; Wulazibieke, Baheti; Aierken, Latipa

    2016-08-24

    Traditional fermented cheese whey (TFCW), containing probiotics, has been used both as a dairy food with ethnic flavor and a medicine for cardiovascular disease, especially regulating blood lipid among Kazakh. We therefore investigated anti-atherosclerotic effects of TFCW in atherosclerotic rabbits and identified lactic acid bacteria (LAB) and yeasts in TFCW. Atherosclerotic rabbits were induced by administration of atherosclerotic diet for 12 weeks and divided randomly into three groups and treated for 4 weeks with Simvastatin (20 mg/kg) or TFCW (25 mg/kg) and (50 mg/kg). In addition, a normal control group and an atherosclerotic group were used for comparison. All drugs were intragastrical administered once daily 10 mL/kg for 4 weeks. Body weight (BW), lipid profiles, C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were tested and theromatous plaques and the number of foam cells and infiltrating fibroblast cells in the thoracic aorta endothelium was evaluated by hematoxylin and eosin stainin. LAB and yeasts were isolated and purified by conventional techniques and identified using morphological and biochemical properties as well as gene sequences analysis. After 4 weeks of treatment, high and low dose TFCW decreased serum TC, TG, LDLC, CRP, VCAM-1 and ICAM-1 (P < 0.05) compared to atherosclerotic group, and increased HDL-C (P < 0.05) compared to normal controls. Histological analysis showed TFCW reduced VCAM-1 expression and formation of atheromatous plaques on the aortic endothelium of atherosclerotic rabbits. Seven classes of LBA from two different genera including Lactobacillus brevis, Lactobacillus kefianofaciens, Lactobacillus helveticus, Lactobacillus Casei, Lactobacillus plantarum, Lactobacillus kefiri and Lactococcus lactic as well as 2 classes of yeasts from two different genera including Saccharomyces unisporus and Issatchenkia orientalis were isolated and identified

  20. [Clinical science relating atherosclerotic diseases and hypertriglyceridemia].

    Science.gov (United States)

    Fujioka, Yoshio

    2013-09-01

    Recent epidemiologic studies and meta-analysis with triglyceride levels are revealing that hypertriglyceridemia is associated with coronary heart diseases independent of other coronary risk factors, although the direct effect of serum triglycerides to atherosclerotic lesion is still uncertain. Multiple genetic and environmental factors from familial hyperlipidemia to food and alcohol intake are implicated in elevating triglycerides. Especially, a number of investigators demonstrated a relationship between atherosclerotic diseases and postprandial hyperlipidemia, which may lead to nonfasting TG elevation. The purpose of this article is to review several clinical studies relating serum fasting and nonfasting triglyceride levels and coronary heart disease, and to discuss whether hypertriglyceridemia initiates atherosclerosis or plays a role as a biomarker for metabolic abnormalities.

  1. Multi-wavelength photoacoustic imaging for monitoring lesion formation during high-intensity focused ultrasound therapy

    Science.gov (United States)

    Wu, Xun; Sanders, Jean; Dundar, Murat; Oralkan, Ömer

    2017-03-01

    Photoacoustic imaging (PAI) can be used to monitor lesion formation during high-intensity focused ultrasound (HIFU) therapy because HIFU changes the optical absorption spectrum (OAS) of the tissue. However, in traditional PAI, the change could be too subtle to be observed either because the OAS does not change very significantly at the imaging wavelength or due to low signal-to-noise ratio in general. We propose a machine-learning-based method for lesion monitoring with multi-wavelength PAI (MWPAI), where PAI is repeated at a sequence of wavelengths and a stack of multi-wavelength photoacoustic (MWPA) images is acquired. Each pixel is represented by a vector and each element in the vector reflects the optical absorption at the corresponding wavelength. Based on the MWPA images, a classifier is trained to classify pixels into two categories: ablated and non-ablated. In our experiment, we create a lesion on a block of bovine tissue with a HIFU transducer, followed by MWPAI in the 690 nm to 950 nm wavelength range, with a step size of 5 nm. In the MWPA images, some of the ablated and non-ablated pixels are cropped and fed to a neural network (NN) as training examples. The NN is then applied to several groups of MWPA images and the results show that the lesions can be identified clearly. To apply MWPAI in/near real-time, sequential feature selection is performed and the number of wavelengths is decreased from 53 to 5 while retaining adequate performance. With a fast-switching tunable laser, the method can be implemented in/near real-time.

  2. Lesion to the nigrostriatal dopamine system disrupts stimulus-response habit formation.

    Science.gov (United States)

    Faure, Alexis; Haberland, Ulrike; Condé, Françoise; El Massioui, Nicole

    2005-03-16

    Acquisition and performance of instrumental actions are assumed to require both action-outcome and stimulus-response (S-R) habit processes. Over the course of extended training, control over instrumental performance shifts from goal-directed action-outcome associations to S-R associations that progressively gain domination over behavior. Lesions of the lateral part of the dorsal striatum disrupt this process, and rats with lesions to the lateral striatum showed selective sensitivity to devaluation of the instrumental outcome (Yin et al., 2004), indicating that this area is necessary for habit formation. The present experiment further explored the basis of this dysfunction by examining the ability of rats subjected to bilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic pathway to develop behavioral autonomy with overtraining. Rats were given extended training on two cued instrumental tasks associating a stimulus (a tone or a light) with an instrumental action (lever press or chain pull) and a food reward (pellets or sucrose). Both tasks were run daily in separate sessions. Overtraining was followed by a test of goal sensitivity by satiety-specific devaluation of the reward. In control animals, one action (lever press) was insensitive to reward devaluation, indicating that it became a habit, whereas the second action (chain pull) was still sensitive to goal devaluation. This result provides evidence that the development of habit learning may depend on the characteristics of the response. In dopamine-depleted rats, lever press and chain pull remained sensitive to reward devaluation, evidencing a role of striatal dopamine transmission in habit formation.

  3. Intracranial Atherosclerotic Disease

    Directory of Open Access Journals (Sweden)

    Maria Khan

    2011-01-01

    Full Text Available Intracranial atherosclerotic disease (ICAD is the most common proximate mechanism of ischemic stroke worldwide. Approximately half of those affected are Asians. For diagnosis of ICAD, intra-arterial angiography is the gold standard to identify extent of stenosis. However, noninvasive techniques including transcranial ultrasound and MRA are now emerging as reliable modalities to exclude moderate to severe (50%–99% stenosis. Little is known about measures for primary prevention of the disease. In terms of secondary prevention of stroke due to intracranial atherosclerotic stenosis, aspirin continues to be the preferred antiplatelet agent although clopidogrel along with aspirin has shown promise in the acute phase. Among Asians, cilostazol has shown a favorable effect on symptomatic stenosis and is of benefit in terms of fewer bleeds. Moreover, aggressive risk factor management alone and in combination with dual antiplatelets been shown to be most effective in this group of patients. Interventional trials on intracranial atherosclerotic stenosis have so far only been carried out among Caucasians and have not yielded consistent results. Since the Asian population is known to be preferentially effected, focused trials need to be performed to establish treatment modalities that are most effective in this population.

  4. High Field Atherosclerotic Plaque MRI

    OpenAIRE

    Yuan, Chun; Wang, Jinnan; Balu, Niranjan

    2012-01-01

    Manifestations of atherosclerotic plaque in different arterial beds range from perfusion deficits to overt ischemia such as stroke and myocardial infarction. Atherosclerotic plaque composition is known to be associated with its propensity to rupture and cause vascular events. MRI of atherosclerotic plaque using clinical 1.5T scanners can detect plaque composition. Plaque MRI at higher field strengths offers both opportunities and challenges to improving the high spatial-resolution and contras...

  5. Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life

    NARCIS (Netherlands)

    Alkemade, F.E.; Gittenberger-Groot, A.C. de; Schiel, A.E.; Munsteren, J.C. van; Hogers, B.; Vliet, L.S.J. van; Poelmann, R.E.; Havekes, L.M.; Dijk, K.W. van; Ruiter, M.C. de

    2007-01-01

    OBJECTIVE - Maternal hypercholesterolemia is associated with a higher incidence and faster progression of atherosclerotic lesions in neonatal offspring. We aimed to determine whether an in utero environment exposing a fetus to maternal hypercholesterolemia and associated risk factors can prime the

  6. [Is regression of atherosclerotic plaque possible?

    Science.gov (United States)

    Páramo, José A; Civeira, Fernando

    As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion ('angiographic paradox'). A number of imaging modalities (vascular ultrasound and virtual histology, MRI, optical coherence tomography, positron tomography, etc.) are used for non-invasive assessment of atherosclerosis; most of them can identify plaque volume and composition beyond lumen stenosis. An 'aggressive' lipid-lowering strategy is able to reduce the plaque burden and the incidence of cardiovascular events; this may be attributable, at least in part, to plaque-stabilizing effects. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Effects of chronic dorsal column lesions on pelvic viscerosomatic convergent medullary reticular formation neurons.

    Science.gov (United States)

    Hubscher, Charles H; Johnson, Richard D

    2004-12-01

    Single medullary reticular formation (MRF) neurons receive multiple somatovisceral convergent inputs originating from many different spinal and cranial nerves, including the pelvic nerve (PN), dorsal nerve of the penis (DNP), and the abdominal branches of the vagus. In a previous study, the input to MRF from the male genitalia was shown to be eliminated with chronic 30-day dorsal hemisection at the T8 spinal level. In this study, the effect of a smaller chronic lesion [dorsal column lesion (DCx)] on MRF neuronal responses was examined. Responses to bilateral electrical stimulation of the DNP remained. MRF neuronal responses to non-noxious (touch/stroke) levels of penile stimulation, however, were eliminated; only responses to noxious pinch remained. No differences were found for the number of neurons responding to noxious distention of the colon between the DCx and control groups. Although no differences were found across these groups for the percent MRF responses to vagal stimulation, the mean response latency for the DCx group was twice the sham-DCx/intact control group. Taken together, these results indicate that the MRF receives at least some of its input from the male genitalia via pathways located within the dorsal columns at the mid-thoracic spinal level.

  8. Reduced contribution of thermally-labile sugar lesions to DNA double-strand break formation after exposure to neutrons.

    Science.gov (United States)

    Singh, Satyendra K; Wu, Wenqi; Stuschke, Martin; Bockisch, Andreas; Iliakis, George

    2012-12-01

    In cells exposed to ionizing radiation, double-strand breaks (DSBs) form within clustered damage sites from lesions disrupting the DNA sugar-phosphate backbone. It is commonly assumed that DSBs form promptly and are immediately detected and processed by the cellular DNA damage response apparatus. However, DSBs also form by delayed chemical conversion of thermally-labile sugar lesions (TLSL) to breaks. We recently reported that conversion of thermally-labile sugar lesions to breaks occurs in cells maintained at physiological temperatures. Here, we investigate the influence of radiation quality on the formation of thermally-labile sugar lesions dependent DSBs. We show that, although the yields of total DSBs are very similar after exposure to neutrons and X rays, the yields of thermally-labile sugar lesions dependent DSBs from neutrons are decreased in comparison to that from X rays. Thus, the yields of prompt DSBs for neutrons are greater than for X rays. Notably, after neutron irradiation the decreased yield of thermally-labile sugar lesion dependent DSBs is strongly cell line dependent, likely reflecting subtle differences in DNA organization. We propose that the higher ionization density of neutrons generates with higher probability prompt DSBs within ionization clusters and renders the ensuing chemical evolution of thermally-labile sugar lesions inconsequential to DNA integrity. Modification of thermally-labile sugar lesion evolution may define novel radiation protection strategies aiming at decreasing DSB formation by chemically preserving thermally-labile sugar lesions until other DSB contributing lesions within the clustered damage site are removed by non-DSB repair pathways.

  9. Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.

    Directory of Open Access Journals (Sweden)

    Helene Hartwig

    Full Text Available Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.

  10. Review: Mechanical Characterization of Carotid Arteries and Atherosclerotic Plaques

    NARCIS (Netherlands)

    Korte, C.L. de; Fekkes, S.; Nederveen, A.J.; Manniesing, R.; Hansen, H.R.

    2016-01-01

    Cardiovascular disease (CVD) is a leading cause of death and is in the majority of cases due to the formation of atherosclerotic plaques in arteries. Initially, thickening of the inner layer of the arterial wall occurs. Continuation of this process leads to plaque formation. The risk of a plaque to

  11. Monitoring the lesion formation during histotripsy treatment using shear wave imaging

    Science.gov (United States)

    Arnal, Bastien; Lee, Wei-Ning; Pernot, Mathieu; Fink, Mathias; Tanter, Mickael

    2012-11-01

    Monitoring the lesion formation induced by histotripsy has mainly relied on the quantitative change in backscatter intensity using ultrasound B-mode imaging. However, how the mechanical properties of the histotripsy-treated tissue region alter during the procedure is yet to be fully investigated. We thus proposed here to monitor such a therapeutic process based on shear modulus estimated by shear wave imaging (SWI). In the therapeutic procedure, a single-element piezo-composite focused transducer (Imasonic, Besançon, France) with a center frequency of 660 kHz, a focal length of 45 mm, and an fnumber of 1 was driven by a function generator (AFG 3101, Tektronix, Beaverton, OR) and a gated RF power amplifier (GA-2500A, RITEC Inc., USA) to generate ultrasound histotripsy pulses. Histotripsy pulses were delivered for 20 seconds and then followed by a 30-second pause and a rapid monitoring step. Such a treatment and monitoring scheme was repeated for 10 mins. Both the reference measurement and monitoring were realized by SWI, where plane shear waves were generated by an 8 MHz linear array probe connected to a prototype ultrasound scanner, and acquired at a frame rate of 10000 Hz. Shear modulus was estimated and mapped in 2D through a time-of-flight algorithm. Gelatin (8%)-agar (2%) phantoms and ex-vivo porcine liver samples were tested. Regions of interests (ROI's) of 2 mm-by-2 mm in both untreated and treated regions were selected to compute the contrast-to-noise ratio (CNR). In all three scenarios where different PD's and PRF's were implemented, during the first 100 seconds of the treatment, 50% decrease in the shear modulus within the histotripsy-targeted zone was already observed, and the CNR of the shear modulus increased by 18 dB. In contrast, the backscatter intensity began to reduce and the corresponding CNR was found to increase by 6 dB only after 120 seconds of treatment. The results demonstrated that SWI can map quantitatively the change of mechanical

  12. Impact of the B Cell Growth Factor APRIL on the Qualitative and Immunological Characteristics of Atherosclerotic Plaques.

    Science.gov (United States)

    Bernelot Moens, Sophie J; van Leuven, Sander I; Zheng, Kang H; Havik, Stefan R; Versloot, Miranda V; van Duivenvoorde, Leonie M; Hahne, Michael; Stroes, Erik S G; Baeten, Dominique L; Hamers, Anouk A J

    2016-01-01

    Studies on the role of B lymphocytes in atherosclerosis development, have yielded contradictory results. Whereas B lymphocyte-deficiency aggravates atherosclerosis in mice; depletion of mature B lymphocytes reduces atherosclerosis. These observations led to the notion that distinct B lymphocyte subsets have different roles. B1a lymphocytes exert an atheroprotective effect, which has been attributed to secretion of IgM, which can be deposited in atherosclerotic lesions thereby reducing necrotic core formation. Tumor necrosis factor (TNF)-family member 'A Proliferation-Inducing Ligand' (APRIL, also known as TNFSF13) was previously shown to increase serum IgM levels in a murine model. In this study, we investigated the effect of APRIL overexpression on advanced lesion formation and composition, IgM production and B cell phenotype. We crossed APRIL transgenic (APRIL-Tg) mice with ApoE knockout (ApoE-/-) mice. After a 12-week Western Type Diet, ApoE-/-APRIL-Tg mice and ApoE-/- littermates showed similar increases in body weight and lipid levels. Histologic evaluation showed no differences in lesion size, stage or necrotic area. However, smooth muscle cell (α-actin stain) content was increased in ApoE-/-APRIL-Tg mice, implying more stable lesions. In addition, increases in both plaque IgM deposition and plasma IgM levels were found in ApoE-/-APRIL-Tg mice compared with ApoE-/- mice. Flow cytometry revealed a concomitant increase in peritoneal B1a lymphocytes in ApoE-/-APRIL-Tg mice. This study shows that ApoE-/-APRIL-Tg mice have increased oxLDL-specific serum IgM levels, potentially mediated via an increase in B1a lymphocytes. Although no differences in lesion size were found, transgenic ApoE-/-APRIL-Tg mice do show potential plaque stabilizing features in advanced atherosclerotic lesions.

  13. The association between Chlamydia pneumoniae DNA in atherosclerotic plaque and major risk factors in patients undergoing coronary artery bypass grafting

    NARCIS (Netherlands)

    Hedayat, Daryoosh Kamal; Jebeli, Mohammad; Mandegar, Mohammad Hossein; Bagheri, Jamshid; Nabavi, Seyed Abbas; Eghtesadi-Araghi, Payam; Mohammadzadeh, Robabeh; Darehzereshki, Ali; Chitsaz, Sam; Abbasi, Ali

    Background and aim: This study was conducted to investigate the prevalence of Chlamydia pneumoniae pathogen inside the atherosclerotic plaque of patients undergoing CABG by using PCR assay and to determine whether there is any association between the presence of bacteria in atherosclerotic lesions

  14. Perforant path lesioning induces sprouting of CA3-associated fibre systems in mouse hippocampal formation

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Hegelund, Iørn V; Poulsen, Frantz R

    2002-01-01

    In comparison to the rat, the anatomy of the mouse hippocampus, and in particular the response to entorhinal cortex lesioning, is less well characterised. Here we studied the axonal sprouting response after lesioning of the entorhinodentate perforant path projection in young adult SJL/J and C57BL...

  15. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Radue, Ernst-Wilhelm; Stuart, William H; Calabresi, Peter A

    2010-01-01

    natalizumab plus IFNbeta-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNbeta-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNbeta-1a and increased in those receiving IFNbeta-1a alone (-277...

  16. Probing Enhanced Double-Strand Break Formation at Abasic Sites within Clustered Lesions in Nucleosome Core Particles.

    Science.gov (United States)

    Banerjee, Samya; Chakraborty, Supratim; Jacinto, Marco Paolo; Paul, Michael D; Balster, Morgan V; Greenberg, Marc M

    2017-01-10

    DNA is rapidly cleaved under mild alkaline conditions at apyrimidinic/apurinic sites, but the half-life is several weeks in phosphate buffer (pH 7.5). However, abasic sites are ∼100-fold more reactive within nucleosome core particles (NCPs). Histone proteins catalyze the strand scission, and at superhelical location 1.5, the histone H4 tail is largely responsible for the accelerated cleavage. The rate constant for strand scission at an abasic site is enhanced further in a nucleosome core particle when it is part of a bistranded lesion containing a proximal strand break. Cleavage of this form results in a highly deleterious double-strand break. This acceleration is dependent upon the position of the abasic lesion in the NCP and its structure. The enhancement in cleavage rate at an apurinic/apyrimidinic site rapidly drops off as the distance between the strand break and abasic site increases and is negligible once the two forms of damage are separated by 7 bp. However, the enhancement of the rate of double-strand break formation increases when the size of the gap is increased from one to two nucleotides. In contrast, the cleavage rate enhancement at 2-deoxyribonolactone within bistranded lesions is more modest, and it is similar in free DNA and nucleosome core particles. We postulate that the enhanced rate of double-strand break formation at bistranded lesions containing apurinic/apyrimidinic sites within nucleosome core particles is a general phenomenon and is due to increased DNA flexibility.

  17. Thrombectomy in Acute Stroke With Tandem Occlusions From Dissection Versus Atherosclerotic Cause

    DEFF Research Database (Denmark)

    Gory, Benjamin; Piotin, Michel; Haussen, Diogo C

    2017-01-01

    BACKGROUND AND PURPOSE: Tandem steno-occlusive lesions were poorly represented in randomized trials and represent a major challenge for endovascular thrombectomy in acute anterior circulation strokes. The impact of the cervical carotid lesion cause (ie, atherosclerotic versus dissection) on outco...

  18. Complement factor C5a induces atherosclerotic plaque disruptions

    Science.gov (United States)

    Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul HA; Bot, Ilze

    2014-01-01

    Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE−/− mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. PMID:25124749

  19. Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome

    NARCIS (Netherlands)

    Peeters, W.; Moll, F.L.; Vink, A.; Spek, P.J. van der; Kleijn, D.P.V. de; Vries, J.-P.P.M. de; Verheijen, J.H.; Newby, A.C.; Pasterkamp, G.

    2011-01-01

    Aims Atherosclerotic plaque rupture and subsequent thrombus formation are the major cause of acute cardiovascular events. Local plaque markers may facilitate detection of the vulnerable plaque and help identify the patient at risk for cardiovascular events. Matrix metalloproteinases (MMPs) are

  20. Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

    Science.gov (United States)

    Kovanen, Petri T; Bot, Ilze

    2017-10-12

    Mast cells are potent actors involved in inflammatory reactions in various tissues, including both in the intimal and the adventitial layers of atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast cells are activated to degranulate, and thereby triggered to release an abundance of preformed inflammatory mediators, notably histamine, heparin, neutral proteases and cytokines stored in their cytoplasmic secretory granules. Depending on the stimulus, mast cell activation may also launch prolonged synthesis and secretion of single bioactive molecules, such as cytokines and derivatives of arachidonic acid. The mast cell-derived mediators may impede the functions of different types of cells present in atherosclerotic lesions, and also compromise the structural and functional integrity of the intimal extracellular matrix. In the adventitial layer of atherosclerotic coronary arteries, mast cells locate next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may activate mast cells to release vasoactive compounds capable of triggering local vasoconstriction. The concerted actions of arterial mast cells have the potential to contribute to the initiation and progression of atherosclerosis, and ultimately to destabilization and rupture of an advanced atherosclerotic plaque with ensuing atherothrombotic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. H-NST induces LEE expression and the formation of attaching and effacing lesions in enterohemorrhagic Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Jonathan A Levine

    Full Text Available Enteropathogenic E. coli (EPEC and enterohemorrhagic E. coli are important causes of morbidity and mortality worldwide. These enteric pathogens contain a type III secretion system (T3SS responsible for the attaching and effacing (A/E lesion phenotype. The T3SS is encoded by the locus of enterocyte effacement (LEE pathogenicity island. The H-NS-mediated repression of LEE expression is counteracted by Ler, the major activator of virulence gene expression in A/E pathogens. A regulator present in EPEC, H-NST, positively affects expression of H-NS regulon members in E. coli K-12, although the effect of H-NST on LEE expression and virulence of A/E pathogens has yet-to-be determined.We examine the effect of H-NST on LEE expression and A/E lesion formation on intestinal epithelial cells. We find that H-NST positively affects the levels of LEE-encoded proteins independently of ler and induces A/E lesion formation. We demonstrate H-NST binding to regulatory regions of LEE1 and LEE3, the first report of DNA-binding by H-NST. We characterize H-NST mutants substituted at conserved residues including Ala16 and residues Arg60 and Arg63, which are part of a potential DNA-binding domain. The single mutants A16V, A16L, R60Q and the double mutant R60Q/R63Q exhibit a decreased effect on LEE expression and A/E lesion formation. DNA mobility shift assays reveal that these residues are important for H-NST to bind regulatory LEE DNA targets. H-NST positively affects Ler binding to LEE DNA in the presence of H-NS, and thereby potentially helps Ler displace H-NS bound to DNA.H-NST induces LEE expression and A/E lesion formation likely by counteracting H-NS-mediated repression. We demonstrate that H-NST binds to DNA and identify arginine residues that are functionally important for DNA-binding. Our study suggests that H-NST provides an additional means for A/E pathogens to alleviate repression of virulence gene expression by H-NS to promote virulence capabilities.

  2. Axonal lesion-induced microglial proliferation and microglial cluster formation in the mouse

    DEFF Research Database (Denmark)

    Dissing-Olesen, L; Ladeby, R; Nielsen, Helle Hvilsted

    2007-01-01

    Microglia are innate immune cells and form the first line of defense of the CNS. Proliferation is a key event in the activation of microglia in acute pathology, and has been extensively characterized in rats, but not in mice. In this study we investigated axonal-lesion-induced microglial prolifer...

  3. Observations on edema formation in the nephrotic syndrome in adults with minimal lesions

    NARCIS (Netherlands)

    Dorhout Mees, E.J.; Roos, J.C.; Boer, P.; Yoe, O.H.; Simatupang, T.A.

    Ten adult patients with the nephrotic syndrome and minimal lesions on renal biopsy were studied while receiving a salt poor diet before and after 13 prednisone-induced remissions. They were selected because the finding of a slight to moderate increase in blood volume in all of them and of an

  4. Variations of bubble cavitation and temperature elevation during lesion formation by high-intensity focused ultrasound.

    Science.gov (United States)

    Zhou, Yufeng; Gao, Xiaobin Wilson

    2013-08-01

    High-intensity focused ultrasound (HIFU) is emerging as an effective therapeutic modality in both thermal ablations for solid tumor/cancer and soft-tissue fragmentation. Mechanical and thermal effects, which play an important role in the HIFU treatment simultaneously, are dependent on the operating parameters and may vary with the progress of therapy. Mechanical erosion in the shape of a "squid," a "dumbbell" lesion with both mechanical and thermal lesions, or a "tadpole" lesion with mechanical erosion at the center and thermal necrosis on the boundary in the transparent gel phantom could be produced correspondingly with the pulse duration of 5-30 ms, which is much longer than histotripsy burst but shorter than the time for tissue boiling, and pulse repetition frequency (PRF) of 0.2-5 Hz. Meanwhile, variations of bubble cavitation (both inertial and stable cavitation) and temperature elevation in the focal region (i.e., z = -2.5, 0, and 2.5 mm) were measured by passive cavitation detection (PCD) and thermocouples during the therapeutic procedure, respectively. Stable cavitation increased with the pulse duration, PRF, and the number of pulses delivered. However, inertial cavitation was found to increase initially and then decrease with long pulse duration and high PRF. Temperature in the pre-focal region is always higher than those at the focal and post-focal position in all tests. Great variations of PCD signals and temperature elevation are due to the generation and persistence of large bubble, which is resistant to collapse and occurs with the increase of pulse duration and PRF. Similar lesion pattern and variations were also observed in ex vivo porcine kidneys. Hyperechoes in the B-mode ultrasound image were comparable to the shape and size of lesions in the dissected tissue. Thermal lesion volume increased with the increase of pulse duration and PRF, but mechanical erosion reached its maximum volume with the pulse duration of 20 ms and PRF of 1

  5. 3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima.

    Science.gov (United States)

    Hazen, S L; Heinecke, J W

    1997-05-01

    Oxidation of LDL may be of pivotal importance in atherogenesis, but the mechanisms that promote oxidation in vivo remain poorly understood. We have explored the possibility that one pathway involves myeloperoxidase, a heme protein secreted by phagocytes. Myeloperoxidase is the only human enzyme known to generate hypochlorous acid (HOCl), a potent oxidizing agent, at physiological halide concentrations. LDL exposed to the complete myeloperoxidase-H2O2-Cl- system underwent chlorination of its protein tyrosyl residues. Treatment of LDL with reagent HOCl resulted in 3-chlorotyrosine formation, implicating HOCl as an intermediate in the enzymatic reaction pathway. In contrast, 3-chlorotyrosine was undetectable in LDL oxidized by hydroxyl radical, copper, iron, hemin, glucose, peroxynitrite, horseradish peroxidase, lactoperoxidase, or lipoxygenase. These results indicate that 3-chlorotyrosine is a specific marker for LDL oxidation by myeloperoxidase. To address the role of myeloperoxidase in promoting LDL oxidation in vivo, we used stable isotope dilution gas chromatography-mass spectrometry to quantify 3-chlorotyrosine in human aortic tissue and in LDL isolated from atherosclerotic lesions. The level of 3-chlorotyrosine in atherosclerotic tissue obtained during vascular surgery was sixfold higher than that of normal aortic intima. Moreover, the level of 3-chlorotyrosine was 30-fold higher in LDL isolated from atherosclerotic intima compared with circulating LDL. The detection of 3-chlorotyrosine in human atherosclerotic lesions indicates that halogenation reactions catalyzed by the myeloperoxidase system of phagocytes constitute one pathway for protein oxidation in vivo. These findings raise the possibility that the myeloperoxidase-H2O2-Cl- system plays a critical role in converting LDL into an atherogenic form.

  6. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Radue, Ernst-Wilhelm; Stuart, William H; Calabresi, Peter A

    2010-01-01

    The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI......) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNbeta-1a 30 microg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving...... natalizumab plus IFNbeta-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNbeta-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNbeta-1a and increased in those receiving IFNbeta-1a alone (-277...

  7. Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions

    Directory of Open Access Journals (Sweden)

    Geou-Yarh Liou

    2016-03-01

    Full Text Available The development of pancreatic cancer requires the acquisition of oncogenic KRas mutations and upregulation of growth factor signaling, but the relationship between these is not well established. Here, we show that mutant KRas alters mitochondrial metabolism in pancreatic acinar cells, resulting in increased generation of mitochondrial reactive oxygen species (mROS. Mitochondrial ROS then drives the dedifferentiation of acinar cells to a duct-like progenitor phenotype and progression to PanIN. This is mediated via the ROS-receptive kinase protein kinase D1 and the transcription factors NF-κB1 and NF-κB2, which upregulate expression of the epidermal growth factor, its ligands, and their sheddase ADAM17. In vivo, interception of KRas-mediated generation of mROS reduced the formation of pre-neoplastic lesions. Hence, our data provide insight into how oncogenic KRas interacts with growth factor signaling to induce the formation of pancreatic cancer.

  8. Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay Formation is Essential for Functional Regeneration

    Directory of Open Access Journals (Sweden)

    Anne Tscherter

    2016-09-01

    Full Text Available Presently there exists no cure for spinal cord injury. However, transplantation of embryonic tissue into spinal cord lesions resulted in axon outgrowth across the lesion site and some functional recovery, fostering hope for future stem cell therapies. Although in vivo evidence for functional recovery is given, the exact cellular mechanism of the graft support remains elusive: either the grafted cells provide a permissive environment for the host tissue to regenerate itself or the grafts actually integrate functionally into the host neuronal network reconnecting the separated spinal cord circuits. We tested the two hypotheses in an in vitro spinal cord lesion model that is based on propagation of activity between two rat organotypic spinal cord slices in culture. Transplantation of dissociated cells from E14 rat spinal cord or forebrain re-established the relay of activity over the lesion site and, thus, provoked functional regeneration. Combining patch-clamp recordings from transplanted cells with network activity measurements from the host tissue on multi-electrode arrays we here show that neurons differentiate from the grafted cells and integrate into the host circuits. Optogenetic silencing of neurons developed from transplanted embryonic mouse forebrain cells provides clear evidence that they replace the lost neuronal connections to relay and synchronize activity between the separated spinal cord circuits. In contrast, transplantation of neurospheres induced neither the differentiation of mature neurons from the grafts nor an improvement of functional regeneration. Together these findings suggest, that the formation of neuronal relays from grafted embryonic cells is essential to re-connect segregated spinal cord circuits.

  9. Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque

    Science.gov (United States)

    Hamblin, Michael R.; Tawakol, Ahmed; Castano, Ana P.; Gad, Faten; Zahra, Touqir; Ahmadi, Atosa; Stern, Jeremy; Ortel, Bernhard; Chirico, Stephanie; Shirazi, Azadeh; Syed, Sakeena; Muller, James E.

    2003-06-01

    Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular

  10. Molecular dynamics of formation of TD lesioned DNA complexed with repair enzyme - onset of the enzymatic repair process

    Energy Technology Data Exchange (ETDEWEB)

    Pinak, Miroslav [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1999-12-01

    To describe the first step of the enzymatic repair process (formation of complex enzyme-DNA), in which the thymine dimer (TD) part is removed from DNA, the 500 picosecond (ps) molecular dynamics (MD) simulation of TD lesioned DNA and part of repair enzyme cell (inclusive of catalytic center - Arg-22, Glu-23, Arg-26 and Thr-2) was performed. TD is UV originated lesion in DNA and T4 Endonuclease V is TD specific repair enzyme. Both molecules were located in the same simulation cell and their relative movement was examined. During the simulation the research was focused on the role of electrostatic energy in formation of complex enzyme-DNA. It is found, that during the first 100 ps of MD, the part of enzyme approaches the DNA surface at the TD lesion, interacts extensively by electrostatic and van der Walls interactions with TD part of DNA and forms complex that lasts stabile for 500 ps of MD. In the beginning of MD, the positive electrostatic interaction energy between part of enzyme and TD ({approx} +10 kcal/mol) drives enzyme towards the DNA molecule. Water-mediated hydrogen bonds between enzyme and DNA help to keep complex stabile. As a reference, the MD simulation of the identical system with native DNA molecule (two native thymines (TT) instead of TD) was performed. In this system the negative electrostatic interaction energy between part of enzyme and TT ({approx} -11 kcal/mol), in contrary to the positive one in the system with TD, doesn't drive enzyme towards DNA and complex is not formed. (author)

  11. Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

    Science.gov (United States)

    Khambata, Rayomand S.; Ghosh, Suborno M.; Rathod, Krishnaraj S.; Thevathasan, Tharssana; Filomena, Federica; Xiao, Qingzhong; Ahluwalia, Amrita

    2017-01-01

    Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO3−) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitrate-fed mice there is reduced systemic leukocyte rolling and adherence, circulating neutrophil numbers, neutrophil CD11b expression, and myeloperoxidase activity compared with wild-type littermates. Moreover, we show in both the ApoE KO mice and using an acute model of inflammation that this effect upon neutrophils results in consequent reductions in inflammatory monocyte expression that is associated with elevations of the antiinflammatory cytokine interleukin (IL)-10. In summary, we demonstrate that inorganic nitrate suppresses acute and chronic inflammation by targeting neutrophil recruitment and that this effect, at least in part, results in consequent reductions in the inflammatory status of atheromatous plaque, and suggest that this effect may have clinical utility in the prophylaxis of inflammatory atherosclerotic disease. PMID:28057862

  12. Detection and characterization of atherosclerotic plaques by Raman probe spectroscopy and optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Matthäus, Christian; Dochow, Sebastian; Egodage, Kokila D.; Schie, Iwan; Romeike, Bernd F.; Brehm, Bernhard R.; Popp, Jürgen

    2017-02-01

    Visualization and characterization of inner arterial plaque depositions is of vital diagnostic interest. Established intravascular imaging techniques provide valuable morphological information, but cannot deliver information about the chemical composition of individual plaques. Probe based Raman spectroscopy offers the possibility for a biochemical characterization of atherosclerotic plaque formations during an intravascular intervention. From post mortem studies it is well known that the severity of a plaque and its stability are strongly correlated with its biochemical composition. Especially the identification of vulnerable plaques remains one of the most important and challenging aspects in cardiology. Thus, specific information about the composition of a plaque would greatly improve the risk assessment and management. Furthermore, knowledge about the composition can offer new therapeutic and medication strategies. Plaque calcifications as well as major lipid components such as cholesterol, cholesterol esters and triglycerides can be spectroscopically easily differentiated. Intravascular optical coherence tomography (OCT) is currently a prominent catheter based imaging technique for the localization and visualization of atherosclerotic plaque depositions. The high resolution of OCT with 10 to 15 µm allows for very detailed characterization of morphological features such as different plaque formations, thin fibrous caps and accurate measurements of lesion lengths. In combination with OCT imaging the obtained spectral information can provide substantial information supporting on on-site diagnosis of various plaque types and therefor an improved risk assessment. The potential and feasibility of combining OCT with Raman spectroscopy is demonstrated on excised plaque samples, as well as under in vivo conditions. Acknowledgements: Financial support from the Carl Zeiss Foundation is greatly acknowledged.

  13. New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-κB pathway.

    Science.gov (United States)

    Tang, Zhi-Han; Peng, Juan; Ren, Zhong; Yang, Jing; Li, Ting-Ting; Li, Tao-Hua; Wang, Zuo; Wei, Dang-Heng; Liu, Lu-Shan; Zheng, Xi-Long; Jiang, Zhi-Sheng

    2017-07-01

    Proprotein convertase subtilisin/kexin 9 (PCSK9) has emerged as a popular target in the development of new cholesterol-lowering drugs and therapeutic interventions for atherosclerosis. PCSK9 could accelerate atherosclerosis through mechanisms beyond the degradation of the hepatic low-density lipoprotein receptor. Several clinical studies suggested that PCSK9 is involved in atherosclerotic inflammation. Accordingly, this study aimed to explore the role of PCSK9 in vascular inflammation that promotes atherosclerotic progression. We examined whether PCSK9 silencing via transduction with the lentivirus-mediated PCSK9 shRNA (LV-PCSK9 shRNA) vector affects the formation of vascular lesions in hyperlipidemia-induced atherosclerosis in apolipoprotein E knockout (apoE KO) mice. In vitro, the effects of PCSK9 on oxLDL-induced macrophages inflammation were investigate using LV-PCSK9 and LV-PCSK9 shRNA for PCSK9 overexpression and PCSK9 silencing. Immunohistochemical analysis showed that PCSK9 expression increased within atherosclerotic plaques in apoE KO mice. These in vivo results showed that the LV-PCSK9 shRNA group of mice developed less aortic atherosclerotic plaques compared with the control group. These lesions also had the reduced number of macrophages and decreased expression of vascular inflammation regulators, such as tumor necrosis factor-α, interleukin 1 beta, monocyte chemoattractant protein-1, toll-like receptor 4 and nuclear factor kappa B (NF-κB). We further showed that PCSK9 overexpression in macrophages in vitro increased the secretion of oxLDL-induced proinflammatory cytokines. PCSK9 overexpression upregulated TLR4 expression and increased p-IκBα levels, IkBα degradation, and NF-κB nuclear translocation in macrophages, but PCSK9 knockdown had the opposite effects in oxLDL-treated macrophages. PCSK9 gene interference could suppress atherosclerosis directly through decreasing vascular inflammation and inhibiting the TLR4/NF-κB signaling pathway without

  14. Complement factor C5a induces atherosclerotic plaque disruptions.

    Science.gov (United States)

    Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul H A; Bot, Ilze

    2014-10-01

    Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE(-/-) mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  15. Radio Frequency Ultrasound Time Series Signal Analysis to Evaluate High-intensity Focused Ultrasound Lesion Formation Status in Tissue.

    Science.gov (United States)

    Mobasheri, Saeedeh; Behnam, Hamid; Rangraz, Parisa; Tavakkoli, Jahan

    2016-01-01

    High-intensity focused ultrasound (HIFU) is a novel treatment modality used by scientists and clinicians in the recent decades. This modality has had a great and significant success as a noninvasive surgery technique applicable in tissue ablation therapy and cancer treatment. In this study, radio frequency (RF) ultrasound signals were acquired and registered in three stages of before, during, and after HIFU exposures. Different features of RF time series signals including the sum of amplitude spectrum in the four quarters of the frequency range, the slope, and intercept of the best-fit line to the entire power spectrum and the Shannon entropy were utilized to distinguish between the HIFU-induced thermal lesion and the normal tissue. We also examined the RF data, frame by frame to identify exposure effects on the formation and characteristics of a HIFU thermal lesion at different time steps throughout the treatment. The results obtained showed that the spectrum frequency quarters and the slope and intercept of the best fit line to the entire power spectrum both increased two times during the HIFU exposures. The Shannon entropy, however, decreased after the exposures. In conclusion, different characteristics of RF time series signal possess promising features that can be used to characterize ablated and nonablated tissues and to distinguish them from each other in a quasi-quantitative fashion.

  16. Vulnerable atherosclerotic plaque detection by resonance Raman spectroscopy

    Science.gov (United States)

    Liu, Cheng-hui; Boydston-White, Susie; Weisberg, Arel; Wang, Wubao; Sordillo, Laura A.; Perotte, Adler; Tomaselli, Vincent P.; Sordillo, Peter P.; Pei, Zhe; Shi, Lingyan; Alfano, Robert R.

    2016-12-01

    A clear correlation has been observed between the resonance Raman (RR) spectra of plaques in the aortic tunica intimal wall of a human corpse and three states of plaque evolution: fibrolipid plaques, calcified and ossified plaques, and vulnerable atherosclerotic plaques (VPs). These three states of atherosclerotic plaque lesions demonstrated unique RR molecular fingerprints from key molecules, rendering their spectra unique with respect to one another. The vibrational modes of lipids, cholesterol, carotenoids, tryptophan and heme proteins, the amide I, II, III bands, and methyl/methylene groups from the intrinsic atherosclerotic VPs in tissues were studied. The salient outcome of the investigation was demonstrating the correlation between RR measurements of VPs and the thickness measurements of fibrous caps on VPs using standard histopathology methods, an important metric in evaluating the stability of a VP. The RR results show that VPs undergo a structural change when their caps thin to 66 μm, very close to the 65-μm empirical medical definition of a thin cap fibroatheroma plaque, the most unstable type of VP.

  17. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    Energy Technology Data Exchange (ETDEWEB)

    Noerenberg, Dominik [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); University of Munich - Grosshadern, Department of Clinical Radiology, Munich (Germany); Ebersberger, Hans U. [Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich (Germany); Diederichs, Gerd; Hamm, Bernd [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Botnar, Rene M. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Makowski, Marcus R. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2016-03-15

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  18. Attaching and effacing (A/E) lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors

    Science.gov (United States)

    Cepeda-Molero, Massiel; Berger, Cedric N.; Walsham, Alistair D. S.; Wemyss-Holden, Simon; Frankel, Gad

    2017-01-01

    Enteropathogenic E. coli (EPEC) is a human pathogen that causes acute and chronic pediatric diarrhea. The hallmark of EPEC infection is the formation of attaching and effacing (A/E) lesions in the intestinal epithelium. Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocyte effacement (LEE), which encode the adhesin intimin, a type III secretion system (T3SS) and six effectors, including the essential translocated intimin receptor (Tir). Seventeen additional effectors are encoded by genes located outside the LEE, in insertion elements and prophages. Here, using a stepwise approach, we generated an EPEC mutant lacking the entire effector genes (EPEC0) and intermediate mutants. We show that EPEC0 contains a functional T3SS. An EPEC mutant expressing intimin but lacking all the LEE effectors but Tir (EPEC1) was able to trigger robust actin polymerization in HeLa cells and mucin-producing intestinal LS174T cells. However, EPEC1 was unable to form A/E lesions on human intestinal in vitro organ cultures (IVOC). Screening the intermediate mutants for genes involved in A/E lesion formation on IVOC revealed that strains lacking non-LEE effector/s have a marginal ability to form A/E lesions. Furthermore, we found that Efa1/LifA proteins are important for A/E lesion formation efficiency in EPEC strains lacking multiple effectors. Taken together, these results demonstrate the intricate relationships between T3SS effectors and the essential role non-LEE effectors play in A/E lesion formation on mucosal surfaces. PMID:29084270

  19. Attaching and effacing (A/E lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors.

    Directory of Open Access Journals (Sweden)

    Massiel Cepeda-Molero

    2017-10-01

    Full Text Available Enteropathogenic E. coli (EPEC is a human pathogen that causes acute and chronic pediatric diarrhea. The hallmark of EPEC infection is the formation of attaching and effacing (A/E lesions in the intestinal epithelium. Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocyte effacement (LEE, which encode the adhesin intimin, a type III secretion system (T3SS and six effectors, including the essential translocated intimin receptor (Tir. Seventeen additional effectors are encoded by genes located outside the LEE, in insertion elements and prophages. Here, using a stepwise approach, we generated an EPEC mutant lacking the entire effector genes (EPEC0 and intermediate mutants. We show that EPEC0 contains a functional T3SS. An EPEC mutant expressing intimin but lacking all the LEE effectors but Tir (EPEC1 was able to trigger robust actin polymerization in HeLa cells and mucin-producing intestinal LS174T cells. However, EPEC1 was unable to form A/E lesions on human intestinal in vitro organ cultures (IVOC. Screening the intermediate mutants for genes involved in A/E lesion formation on IVOC revealed that strains lacking non-LEE effector/s have a marginal ability to form A/E lesions. Furthermore, we found that Efa1/LifA proteins are important for A/E lesion formation efficiency in EPEC strains lacking multiple effectors. Taken together, these results demonstrate the intricate relationships between T3SS effectors and the essential role non-LEE effectors play in A/E lesion formation on mucosal surfaces.

  20. SR 11302, an AP-1 Inhibitor, Reduces Metastatic Lesion Formation in Ex Vivo 4D Lung Cancer Model.

    Science.gov (United States)

    Mishra, Dhruva Kumar; Kim, Min P

    2017-12-01

    Activator protein (AP) -1 is a transcription factor, plays important role in cell differentiation, proliferation and apoptosis. Analysis of tumor cells grown on ex vivo 4D lung cancer model shows increase in components of AP-1, c-Fos and c-Jun in circulating tumor cells (CTC) compared to primary tumor. Our aim was to determine whether the AP-1 inhibitor SR11302 reduces metastatic lesion formation in the 4D model. Human lung cancer cell lines A549, H1299, and H460 were grown in the 4D model and treated with SR11302 (1 μM). We compared the number of cells in the metastatic site upon SR11302 treatment and number of viable CTCs isolated from the 4D model with parental cells treated/untreated with SR11302 on a petri dish. There were significantly fewer tumor cells per high-power field on metastatic site in 4D model seeded with H460 (p = 0.009), A549 (p = 0.01), or H1299 (p = 0.02) cells treated with SR11302. Furthermore, the CTCs from SR11302 treated 4D models, seeded with H460 (p = 0.04), A549 (p = 0.008), or H1299 (p = 0.01) cells had significantly fewer viable tumor cells after 4 days in culture than the respective untreated control. However, the SR11302 had no impact on the viability of parental H460 (p = 0.87), A549 (p = 0.93), or H1299 (p = 0.25) cells grown on a petri dish (2D). SR11302 reduces metastatic lesion formation in the ex vivo 4D lung cancer model due to the presence of an independent yet common pathway among three cell lines. The ex vivo 4D model may provide a tool to better understand the complex process of metastasis.

  1. Hemodynamic characteristics of hyperplastic remodeling lesions in cerebral aneurysms.

    Directory of Open Access Journals (Sweden)

    Kazuhiro Furukawa

    Full Text Available Hyperplastic remodeling (HR lesions are sometimes found on cerebral aneurysm walls. Atherosclerosis is the results of HR, which may cause an adverse effect on surgical treatment for cerebral aneurysms. Previous studies have demonstrated that atherosclerotic changes had a correlation with certain hemodynamic characteristics. Therefore, we investigated local hemodynamic characteristics of HR lesions of cerebral aneurysms using computational fluid dynamics (CFD.Twenty-four cerebral aneurysms were investigated using CFD and intraoperative video recordings. HR lesions and red walls were confirmed on the intraoperative images, and the qualification points were determined on the center of the HR lesions and the red walls. The qualification points were set on the virtual operative images for evaluation of wall shear stress (WSS, normalized WSS (NWSS, oscillatory shear index (OSI, relative residence time (RRT, and aneurysm formation indicator (AFI. These hemodynamic parameters at the qualification points were compared between HR lesions and red walls.HR lesions had lower NWSS, lower AFI, higher OSI and prolonged RRT compared with red walls. From analysis of the receiver-operating characteristic curve for hemodynamic parameters, OSI was the most optimal hemodynamic parameter to predict HR lesions (area under the curve, 0.745; 95% confidence interval, 0.603-0.887; cutoff value, 0.00917; sensitivity, 0.643; specificity, 0.893; P<0.01. With multivariate logistic regression analyses using stepwise method, NWSS was significantly associated with the HR lesions.Although low NWSS was independently associated with HR lesions, OSI is the most valuable hemodynamic parameter to distinguish HR lesions from red walls.

  2. Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques

    Science.gov (United States)

    Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

    2016-03-01

    Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification areas. We also show that calcification morphology and the plaque’s collagen content--two determinants of atherosclerotic plaque stability--are interlinked.

  3. Anti-atherosclerotic effects of konjac

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2015-04-01

    Full Text Available Definition: The Konjac plant comes from the genus Amorphophallus. Japanese food uses Konjac cake. Konjac contains almost no calories and a great amount of dietary fiber. Here, we reviewed possible anti-atherosclerotic effects of konjac, using the search Pubmed ®. Konjac ingestion is likely beneficially associated with obesity, blood pressure, lipid and glucose metabolism. However, evidence is lacking on the relationship between konjac ingestion and development of atherosclerotic diseases. To more fully understand the anti-atherosclerotic effects of konjac, future studies, preferably with larger numbers of subjects, will be performed.

  4. Circumferential lesion formation around the pulmonary veins in the left atrium with focused ultrasound using a 2D-array endoesophageal device: a numerical study

    Energy Technology Data Exchange (ETDEWEB)

    Pichardo, Samuel; Hynynen, Kullervo [Imaging Research-Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room C713, Toronto, ON M4N 3M5 (Canada)

    2007-08-21

    Atrial fibrillation (AF) is the most frequently sustained cardiac arrhythmia affecting humans. The electrical isolation by ablation of the pulmonary veins (PVs) in the left atrium (LA) of the heart has been proven as an effective cure of AF. The ablation consists mainly in the formation of a localized circumferential thermal coagulation of the cardiac tissue surrounding the PVs. In the present numerical study, the feasibility of producing the required circumferential lesion with an endoesophageal ultrasound probe is investigated. The probe operates at 1 MHz and consists of a 2D array with enough elements (114 x 20) to steer the acoustic field electronically in a volume comparable to the LA. Realistic anatomical conditions of the thorax were considered from the segmentation of histological images of the thorax. The cardiac muscle and the blood-filled cavities in the heart were identified and considered in the sound propagation and thermal models. The influence of different conditions of the thermal sinking in the LA chamber was also studied. The circumferential ablation of the PVs was achieved by the sum of individual lesions induced with the proposed device. Different scenarios of lesion formation were considered where ultrasound exposures (1, 2, 5 and 10 s) were combined with maximal peak temperatures (60, 70 and 80 {sup 0}C). The results of this numerical study allowed identifying the limits and best conditions for controlled lesion formation in the LA using the proposed device. A controlled situation for the lesion formation surrounding the PVs was obtained when the targets were located within a distance from the device in the range of 26 {+-} 7 mm. When combined with a maximal temperature of 70 {sup 0}C and an exposure time between 5 and 10 s, this distance ensured preservation of the esophageal structures, controlled lesion formation and delivery of an acoustic intensity at the transducer surface that is compatible with existing materials. With a peak

  5. Circumferential lesion formation around the pulmonary veins in the left atrium with focused ultrasound using a 2D-array endoesophageal device: a numerical study

    Science.gov (United States)

    Pichardo, Samuel; Hynynen, Kullervo

    2007-08-01

    Atrial fibrillation (AF) is the most frequently sustained cardiac arrhythmia affecting humans. The electrical isolation by ablation of the pulmonary veins (PVs) in the left atrium (LA) of the heart has been proven as an effective cure of AF. The ablation consists mainly in the formation of a localized circumferential thermal coagulation of the cardiac tissue surrounding the PVs. In the present numerical study, the feasibility of producing the required circumferential lesion with an endoesophageal ultrasound probe is investigated. The probe operates at 1 MHz and consists of a 2D array with enough elements (114 × 20) to steer the acoustic field electronically in a volume comparable to the LA. Realistic anatomical conditions of the thorax were considered from the segmentation of histological images of the thorax. The cardiac muscle and the blood-filled cavities in the heart were identified and considered in the sound propagation and thermal models. The influence of different conditions of the thermal sinking in the LA chamber was also studied. The circumferential ablation of the PVs was achieved by the sum of individual lesions induced with the proposed device. Different scenarios of lesion formation were considered where ultrasound exposures (1, 2, 5 and 10 s) were combined with maximal peak temperatures (60, 70 and 80 °C). The results of this numerical study allowed identifying the limits and best conditions for controlled lesion formation in the LA using the proposed device. A controlled situation for the lesion formation surrounding the PVs was obtained when the targets were located within a distance from the device in the range of 26 ± 7 mm. When combined with a maximal temperature of 70 °C and an exposure time between 5 and 10 s, this distance ensured preservation of the esophageal structures, controlled lesion formation and delivery of an acoustic intensity at the transducer surface that is compatible with existing materials. With a peak temperature of 70

  6. Evaluation of five DNA extraction methods for purification of DNA from atherosclerotic tissue and estimation of prevalence of Chlamydia pneumoniae in tissue from a Danish population undergoing vascular repair

    DEFF Research Database (Denmark)

    Mygind, Tina; Østergaard, Lars; Birkelund, Svend

    2003-01-01

    To date PCR detection of Chlamydia pneumoniae DNA in atherosclerotic lesions from Danish patients has been unsuccessful. To establish whether non-detection was caused by a suboptimal DNA extraction method, we tested five different DNA extraction methods for purification of DNA from atherosclerotic...

  7. Magnetic force microscopy of atherosclerotic plaque

    National Research Council Canada - National Science Library

    T A Alexeeva; S V Gorobets; O Yu Gorobets; I V Demianenko; O M Lazarenko

    2014-01-01

    In this work by methods of scanning probe microscopy, namely by atomic force microscopy and magnetic force microscopy the fragments of atherosclerotic plaque section of different nature were investigated...

  8. Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.

    Directory of Open Access Journals (Sweden)

    Kurt Reifenberg

    Full Text Available Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1 and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE(-/- mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet as indicated by aortic plaque area en face (p<0.05. Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD, significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD, significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.

  9. Anti-Atherosclerotic Effects of a Phytoestrogen-Rich Herbal Preparation in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Veronika A. Myasoedova

    2016-08-01

    7.1% in placebo recipients (NS. The differences between lipid changes in the isoflavonoid-rich herbal preparation and placebo recipients did not reach statistical significance (p > 0.05. Nevertheless, the mean cIMT progression was significantly lower in isoflavonoid-rich herbal preparation recipients as compared to the placebo group (6 μm, or <1%, versus 100 μm, or 13%; p < 0.001 for the difference. The growth of existing atherosclerotic plaques in isoflavonoid-rich herbal preparation recipients was inhibited by 1.5-fold (27% versus 41% in the placebo group. The obtained results demonstrate that the use of isoflavonoid-rich herbal preparation in postmenopausal women may suppress the formation of new atherosclerotic lesions and reduce the progression of existing ones, thus promising new drug for anti-atherosclerotic therapy. Nevertheless, further studies are required to confirm these findings.

  10. EXTRACRANIAL NON-ATHEROSCLEROTIC PATHOLOGY OF THE CAROTID ARTERY IN THE CAUSES OF ACUTE ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    I. P. Dudanov

    2017-01-01

    Full Text Available Purpose. We present the experience of treatment of patients with cerebral vascular accident by the ischemic type, the cause of which was non-atherosclerotic lesion of brachiocephalic arteries.Materials and methods. During 2011–2015 years 4118 patients with acute ischemic stroke were observed. Of these, 589 patients (14.3% were operated in the acute period of stroke in the period from 4–6 hours to 14 days. The cause of the stroke was various types of pathology of the extracranial divisions of the brachiocephalic arteries (EDBA. Of this number, with atherosclerotic carotid artery stenoses, 336 patients (57.1% were operated on, with non-atherosclerotic pathology of carotid arteries — 253 patients (42.9%. Of these 253 patients, dissection of the intima of the carotid arteries was detected in 10 (3.9% patients, aneurysms in the extracranial segment of the ECA and ICA were detected in 14 (5.5%, and 229 (90.6% revealed various types of tortuosity and kinks carotid arteries and fibrous dysplasia. All patients are operated on. Various types of reconstructions of carotid arteries with a good clinical effect have been performed. There were no lethal outcomes.Concusions. The data obtained in the study confirm the opinion that not only atherosclerotic lesions of the ICA are an indication for surgical treatment at an early date. This stage is an important part of the comprehensive rehabilitation of patients with acute ischemic stroke.

  11. Vascular neuropeptide Y contributes to atherosclerotic plaque progression and perivascular mast cell activation.

    Science.gov (United States)

    Lagraauw, H Maxime; Westra, Marijke M; Bot, Martine; Wezel, Anouk; van Santbrink, Peter J; Pasterkamp, Gerard; Biessen, Erik A L; Kuiper, Johan; Bot, Ilze

    2014-07-01

    Neuropeptide Y is an abundantly expressed neurotransmitter capable of modulating both immune and metabolic responses related to the development of atherosclerosis. NPY receptors are expressed by a number of vascular wall cell types, among which mast cells. However, the direct effects of NPY on atherosclerotic plaque development and progression remain to be investigated. In this study we thus aimed to determine whether NPY is expressed in atherosclerotic plaques and to establish its role in atherosclerotic plaque development. NPY expression was seen to be increased up to 2-fold in unstable human endarterectomy plaques, as compared to stable plaques, and to be significantly upregulated during lesion progression in apoE(-/-) mice. In apoE(-/-) mice focal overexpression of NPY in the carotid artery significantly increased atherosclerotic plaque size compared to controls, while plaque composition was unaffected. Interestingly, perivascular mast cell activation was significantly higher in the NPY-overexpressing mice, suggesting that NPY may impact plaque progression in part via mast cell activation. Furthermore, in vitro NPY-induced murine mast cell activation resulted in the release of pro-atherogenic mediators including IL-6 and tryptase. Our data show that NPY expression is increased during atherogenesis and in particular in unstable plaques. Furthermore, perivascular overexpression of NPY promoted plaque development and perivascular mast cell activation, suggestive of a role for NPY-induced mast cell activation in lesion progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration.

    Science.gov (United States)

    Xu, Suining; Li, Lihua; Yan, Jinchuan; Ye, Fei; Shao, Chen; Sun, Zhen; Bao, Zhengyang; Dai, Zhiyin; Zhu, Jie; Jing, Lele; Wang, Zhongqun

    2018-01-01

    Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration. In vivo study and in vitro study were performed. For the in vivo investigation, CML/CD36 accelerated atherosclerotic progression via promoting the accumulation of macrophage-derived foam cells in aorta and inhibited macrophage-derived foam cells in aorta migrating to the para-aorta lymph node of diabetic apoE -/- mice. For the in vitro investigation, CML/CD36 inhibited RAW264.7-derived foam cell migration through NOX-derived ROS, FAK phosphorylation, Arp2/3 complex activation and F-actin polymerization. Thus, we concluded that CML/CD36 inhibited foam cells of plaque migrating to para-aorta lymph nodes, accelerating atherosclerotic progression. The corresponding mechanism may be via free cholesterol, ROS generation, p-FAK, Arp2/3, F-actin polymerization. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Macrophage Liver Kinase B1 Inhibits Foam Cell Formation and Atherosclerosis.

    Science.gov (United States)

    Liu, Zhaoyu; Zhu, Huaiping; Dai, Xiaoyan; Wang, Cheng; Ding, Ye; Song, Ping; Zou, Ming-Hui

    2017-10-13

    LKB1 (liver kinase B1) is a serine/threonine kinase and tumor suppressor, which regulates the homeostasis of hematopoietic cells and immune responses. Macrophages transform into foam cells upon taking-in lipids. No role for LKB1 in foam cell formation has previously been reported. We sought to establish the role of LKB1 in atherosclerotic foam cell formation. LKB1 expression was examined in human carotid atherosclerotic plaques and in western diet-fed atherosclerosis-prone Ldlr -/- and ApoE -/- mice. LKB1 expression was markedly reduced in human plaques when compared with nonatherosclerotic vessels. Consistently, time-dependent reduction of LKB1 levels occurred in atherosclerotic lesions in western diet-fed Ldlr -/- and ApoE -/- mice. Exposure of macrophages to oxidized low-density lipoprotein downregulated LKB1 in vitro. Furthermore, LKB1 deficiency in macrophages significantly increased the expression of SRA (scavenger receptor A), modified low-density lipoprotein uptake and foam cell formation, all of which were abolished by blocking SRA. Further, we found LKB1 phosphorylates SRA resulting in its lysosome degradation. To further investigate the role of macrophage LKB1 in vivo, ApoE -/- LKB1 fl/fl LysM cre and ApoE -/- LKB1 fl/fl mice were fed with western diet for 16 weeks. Compared with ApoE -/- LKB1 fl/fl wild-type control, ApoE -/- LKB1 fl/fl LysM cre mice developed more atherosclerotic lesions in whole aorta and aortic root area, with markedly increased SRA expression in aortic root lesions. We conclude that macrophage LKB1 reduction caused by oxidized low-density lipoprotein promotes foam cell formation and the progression of atherosclerosis. © 2017 American Heart Association, Inc.

  14. Potent Vasoconstrictor Kisspeptin-10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist.

    Science.gov (United States)

    Sato, Kengo; Shirai, Remina; Hontani, Mina; Shinooka, Rina; Hasegawa, Akinori; Kichise, Tomoki; Yamashita, Tomoyuki; Yoshizawa, Hayami; Watanabe, Rena; Matsuyama, Taka-Aki; Ishibashi-Ueda, Hatsue; Koba, Shinji; Kobayashi, Youichi; Hirano, Tsutomu; Watanabe, Takuya

    2017-04-14

    Kisspeptin-10 (KP-10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor, GPR54, have currently received much attention in relation to pre-eclampsia. However, it still remains unknown whether KP-10 could affect atherogenesis. We evaluated the effects of KP-10 on human umbilical vein endothelial cells, human monocyte-derived macrophages, human aortic smooth muscle cells in vitro, and atherosclerotic lesions in apolipoprotein E-deficient (ApoE-/-) mice in vivo. KP-10 significantly increased the adhesion of human monocytes to human umbilical vein endothelial cells, which was significantly inhibited by pretreatment with P234, a GPR54 antagonist. KP-10 stimulated mRNA expression of tumor necrosis factor-α, interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin in human umbilical vein endothelial cells. KP-10 significantly enhanced oxidized low-density lipoprotein-induced foam cell formation associated with upregulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in human monocyte-derived macrophages. In human aortic smooth muscle cells, KP-10 significantly suppressed angiotensin II-induced migration and proliferation, but enhanced apoptosis and activities of matrix metalloproteinase (MMP)-2 and MMP-9 by upregulation of extracellular signal-regulated kinase 1 and 2, p38, Bcl-2-associated X protein, and caspase-3. Four-week-infusion of KP-10 into ApoE-/- mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration and vascular inflammation as well as decreased intraplaque vascular smooth muscle cells contents. Proatherosclerotic effects of endogenous and exogenous KP-10 were completely canceled by P234 infusion in ApoE-/- mice. Our results suggest that KP-10 may contribute to accelerate the progression and instability of atheromatous plaques, leading to plaque rupture. The GPR54 antagonist may be

  15. Large mobile thrombus in non-atherosclerotic thoracic aorta as the source of peripheral arterial embolism

    Directory of Open Access Journals (Sweden)

    Brkovic Zoran

    2005-11-01

    Full Text Available Abstract The presence of thrombi in the atherosclerotic and/or aneurysmatic aorta with peripheral arterial embolism is a common scenario. Thrombus formation in a morphologically normal aorta, however, is a rare event. A 50 years old woman was admitted to the mergency department for pain, coldness, and anesthesia in the the left foot. She had a 25 years history of cigarette smoking, a history of postmenopausal hormone replacement therapy (HRT, hypercholesterolemia and hyperfibrinogenemia. An extensive serologic survey for hypercoagulability, including antiphospholipid antibodies, and vasculitis disorders was negative. Transesophageal echocardiography revealed a large, pedunculated and hypermobile thrombus attached to the aortic wall 5 cm distal of the left subclavian artery. The patient was admitted to the surgery department, where a 15 cm long fresh, parietal thrombus could be removed from the aorta showing no macroscopic wall lesions or any other morphologic abnormalities. This case report demonstrates the possibility of evolving a large, pedunculated thrombus in a morphologically intact aorta in a postmenopausal woman with thrombogenic conditions such as hyperfibrinogenemia, hypercholesterolemia, smoking and HRT. For these patients, profiling the individual risk and weighing the benefits against the potential risks is warranted before prescribing HRT.

  16. Vorapaxar in atherosclerotic disease management.

    Science.gov (United States)

    Cheng, Judy W M; Colucci, Vincent; Howard, Patricia A; Nappi, Jean M; Spinler, Sarah A

    2015-05-01

    To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases. Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). Two phase III clinical trials with vorapaxar have been published. In patients with non-ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke. Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient's individual bleeding risk. © The Author(s) 2015.

  17. Laboratory model to evaluate the influence of stress and corrosion in the formation of non-carious cervical lesions

    OpenAIRE

    Leal, Noélia Maria de Sousa; Benigno, Maria Ivone Mendes; Silva, Juscelino Lopes; Pedrosa,Simone Soares; ALVES, Eliane Bemerguy; Ballester,Rafael Yagüe

    2014-01-01

    Objective: To conceive and test a laboratory model that simulates the multifactorial etiology of non-carious cervical lesions. The model enables researchers to assess the pathological process with increasing levels of complexity, focusing on tension and corrosion. The model is aimed at clarifying the mechanisms that lead to the development of these lesions. Methods: Specimens were manufactured from bovine incisors cut into 18 × 3 × 3 mm sticks, with a notch in the cervical region facing the p...

  18. Induction of atherosclerotic plaque rupture in apolipoprotein E-/- mice after adenovirus-mediated transfer of p53

    NARCIS (Netherlands)

    Thüsen, J.H. von der; Vlijmen, B.J.M. van; Hoeben, R.C.; Kockx, M.M.; Havekes, L.M.; Berkel, T.J.C. van; Biessen, E.A.L.

    2002-01-01

    Background - The presence of the tumor-suppressor gene p53 in advanced atherosclerotic plaques and the sensitivity to p53-induced cell death of smooth muscle cells isolated from these plaques have fueled speculation about the role of p53 in lesion destabilization and plaque rupture. In this study,

  19. 64Cu-DOTATATE PET/MRI for detection of activated macrophages in carotid atherosclerotic plaques

    DEFF Research Database (Denmark)

    Pedersen, Sune Folke; Sandholt, Benjamin Vikjær; Keller, Sune Høgild

    2015-01-01

    OBJECTIVE: A feature of vulnerable atherosclerotic plaques of the carotid artery is high activity and abundance of lesion macrophages. There is consensus that this is of importance for plaque vulnerability, which may lead to clinical events, such as stroke and transient ischemic attack. We used...... polymerase chain reaction in the final multivariate model, indicating that 64Cu-DOTATATE PET is detecting alternatively activated macrophages. This association could potentially improve noninvasive identification and characterization of vulnerable plaques....

  20. Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel 18F-Folate Radiotracer

    Directory of Open Access Journals (Sweden)

    Adrienne Müller

    2014-03-01

    Full Text Available Folate receptor β (FR-β is overexpressed on activated, but not resting, macrophages involved in a variety of inflammatory and autoimmune diseases. A pivotal step in atherogenesis is the subendothelial accumulation of macrophages. In nascent lesions, they coordinate the scavenging of lipids and cellular debris to define the likelihood of plaque inflammation and eventually rupture. In this study, we determined the presence of FR-β-expressing macrophages in atherosclerotic lesions by the use of a fluorine-18-labeled folate-based radiotracer. Human endarterectomized specimens were used to measure gene expression levels of FR-β and CD68. Increased FR-β and CD68 levels were found in atherosclerotic plaques compared to normal artery walls by quantitative real-time polymerase chain reaction. Western blotting and immunohistochemistry demonstrated prominent FR-β protein levels in plaques. FR- β-positive cells colocalized with activated macrophages (CD68 in plaque tissue. Carotid sections incubated with 3′-aza-2′- [18F]fluorofolic acid displayed increased accumulation in atherosclerotic plaques through in vitro autoradiography. Specific binding of the radiotracer correlated with FR-β-expressing macrophages. These results demonstrate high FR-β expression in atherosclerotic lesions of human carotid tissue correlating with CD68-positive macrophages. Areas of high 3′-aza-2′-[18F]fluorofolic acid binding within the lesions represented FR-β-expressing macrophages. Selectively targeting FR-β-positive macrophages through folate-based radiopharmaceuticals may be useful for noninvasive imaging of plaque inflammation.

  1. Characterization of HSP27 phosphorylation sites in human atherosclerotic plaque secretome

    DEFF Research Database (Denmark)

    Durán, Mari-Carmen; Boeri-Erba, Elisabetta; Mohammed, Shabaz

    2007-01-01

    Atherosclerosis is one of the main causes of death in developed countries. Atheroma plaque formation is promoted by the interaction between the cells conforming the arterial wall, smooth muscle cells, and endothelial cells, together with lipoproteins and inflammatory cells (mainly macrophages and T......-lymphocytes). These interactions can be mediated by proteins secreted from these cells, which therefore exert an important role in the atherosclerotic process. We recently described a novel strategy for the characterization of the human atherosclerotic plaque secretome, combining two-dimensional gel electrophoresis and mass......, the role that phosphorylated HSP27 could play in the atherosclerotic process is actually under study. The present work shows the strategies employed to characterize the phosphorylation in the HSP27 secreted by atheroma plaque samples. The application of liquid chromatography tandem mass spectrometry (MS...

  2. Anti-atherosclerotic effects of tomatoes

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    Hidekatsu Yanai

    2017-06-01

    Full Text Available Tomatoes are rich in lycopene, which causes the red coloring of tomatoes. Several reports have suggested lycopene plays a role in the prevention of cardiovascular diseases. In this study, we systematically reviewed the interventional studies using tomatoes or tomato products to understandtheanti-atherosclerotic effects of the tomatoas a functional food. We found that a significantnumber of interventional studies reportedtheanti-atherosclerotic effects of tomatoes, includinganti-obesity effects, hypotensiveeffects, improvement of lipid/glucose metabolismand endothelial function, anti-oxidative and anti-inflammatory effect, and anti-platelet effect; however, the anti-platelet effect was disagreed uponby some studies. Furthermore, we discoveredcooking methods significantlyaffect anti-atherosclerotic effects of tomatoes.

  3. Cardiovascular magnetic resonance in carotid atherosclerotic disease

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    Chen Huijun

    2009-12-01

    Full Text Available Abstract Atherosclerosis is a chronic, progressive, inflammatory disease affecting many vascular beds. Disease progression leads to acute cardiovascular events such as myocardial infarction, stroke and death. The diseased carotid alone is responsible for one third of the 700,000 new or recurrent strokes occurring yearly in the United States. Imaging plays an important role in the management of atherosclerosis, and cardiovascular magnetic resonance (CMR of the carotid vessel wall is one promising modality in the evaluation of patients with carotid atherosclerotic disease. Advances in carotid vessel wall CMR allow comprehensive assessment of morphology inside the wall, contributing substantial disease-specific information beyond luminal stenosis. Although carotid vessel wall CMR has not been widely used to screen for carotid atherosclerotic disease, many trials support its potential for this indication. This review summarizes the current state of knowledge regarding carotid vessel wall CMR and its potential clinical application for management of carotid atherosclerotic disease.

  4. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

    2013-05-10

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  5. Modifying effect of dietary sesaminol glucosides on the formation of azoxymethane-induced premalignant lesions of rat colon.

    OpenAIRE

    Sheng, Hongqiang; Hirose, Yoshinobu; Hata, Kazuya; Zheng, Qiao; KUNO, TOSHIYA; Asano, Nami; Yamada, Yasuhiro; Hara, Akira; Osawa, Toshihiko; Mori, Hideki

    2007-01-01

    Dietary modulation of cancer & cancer biomarkers Dietary item or component studied:sesameOutcome studied (cancer or cancer biomarker):colon cancerStudy type (in vitro, animals, humans): 55 F344 male ratsTissue/biological material/sample size:blood, cryps sectionsMode of exposure (if in vivo):through dietImpact on outcome (including dose-response):AOM alone number of ACF=84+/-37.5, number of cryps per lesion=3.38+/-0.33AOM+250ppm SG number of ACF=79+/-26.6, number of cryps per lesion=3.34+/-0....

  6. Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

    Science.gov (United States)

    Li, Hong-Peng; Komuta, Yukari; Kimura-Kuroda, Junko; van Kuppevelt, Toin H.

    2013-01-01

    Abstract Dermatan sulfate (DS) is synthesized from chondroitin sulfate (CS) by epimerization of glucuronic acid of CS to yield iduronic acid. In the present study, the role of CS and DS was examined in mice that received transection of nigrostriatal dopaminergic pathway followed by injection of glycosaminoglycan degrading enzymes into the lesion site. Two weeks after injury, fibrotic and glial scars were formed around the lesion, and transected axons did not regenerate beyond the fibrotic scar. Injection of chondroitinase ABC (ChABC), which degrades both CS and DS, completely suppressed the fibrotic scar formation, reduced the glial scar, and promoted the regeneration of dopaminergic axons. Injection of the DS-degrading enzyme chondroitinase B (ChB) also yielded similar results. By contrast, injection of chondroitinase AC (ChAC), a CS-degrading enzyme, did not suppress the fibrotic and glial scar formation, but reduced CS immunoreactivity and promoted the axonal regeneration. Addition of transforming growth factor-β1 (TGF-β1) to a co-culture of meningeal fibroblasts and cerebral astrocytes induces a fibrotic scar-like cell cluster. The effect of TGF-β1 on cluster formation was suppressed by treatment with ChABC or ChB, but not by ChAC. TGF-β1-induced cell cluster repelled neurites of neonatal cerebellar neurons, but addition of ChABC or ChAC suppressed the inhibitory property of clusters on neurite outgrowth. The present study is the first to demonstrate that DS and CS play different functions after brain injury: DS is involved in the lesion scar formation, and CS inhibits axonal regeneration. PMID:23438307

  7. Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Kazuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Senokuchi, Takafumi; Ishii, Norio; Kinoshita, Hiroyuki; Yamada, Sarie; Murakami, Saiko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Nakao, Saya [Department of Environmental & Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto (Japan); Motoshima, Hiroyuki; Kondo, Tatsuya; Kukidome, Daisuke; Kawasaki, Shuji [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Kawada, Teruo [Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan)

    2015-01-30

    Highlights: • Statins induce PPARγ activation in vascular smooth muscle cells. • Statin-induced PPARγ activation is mediated by COX-2 expression. • Statins suppress cell migration and proliferation in vascular smooth muscle cells. • Statins inhibit LPS-induced inflammatory responses by PPARγ activation. • Fluvastatin suppress the progression of atherosclerosis and induces PPARγ activation in the aorta of apoE-deficient mice. - Abstract: The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe{sup −/−} mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe{sup −/−} mice. In conclusion, statins mediate anti-atherogenic effects

  8. Mathematical models for atherosclerotic plaque evolution

    NARCIS (Netherlands)

    Bulelzai, M.A.K.

    2013-01-01

    Atherosclerosis is a disease in which low density lipoproteins (LDL) accumulate in the arterial wall due to an inflammatory response, which is triggered by the oxidation of LDL molecules that are already present in the arterial wall. Progression of atherosclerotic plaques involves many components

  9. Modulography: elasticity imaging of atherosclerotic plaques

    NARCIS (Netherlands)

    R. Baldewsing (Radj)

    2006-01-01

    textabstractModulography is an experimental elasticity imaging method. It has potential to become an all-in-one in vivo tool (a) for detecting vulnerable atherosclerotic coronary plaques, (b) for assessing information related to their rupture-proneness and (c) for imaging their elastic material

  10. In vitro effect of fluoride oral hygiene tablets on artificial caries lesion formation and remineralization in human enamel

    Directory of Open Access Journals (Sweden)

    Kremniczky Thomas

    2009-10-01

    Full Text Available Abstract Background Aim of this in-vitro-study was to assess the remineralization potential of a tooth cleaning tablet with different fluoride content. Methods Twenty three caries free impacted third molars were examined, enamel surfaces were wax coated leaving two 3 × 4 mm windows for exposure to demineralization/remineralization cycles. The teeth were randomly assigned to 4 groups of 5 control and 6 experimental teeth. Demineralization by standardised HEC-gel, pH 4.7 at 37°C for 72 h, was alternated by rinsing in remineralization solution, pH 7.0 at 37°C for 72 h, total challenge time 432 h. The negative control group N was treated during remineralization cycles with saline; positive control group P was treated with remineralization solution; experimental group D1 was exposed to remineralization solution containing Denttabs®-tablets with 1450 ppm F; experimental group D2 was exposed to remineralization solution and Denttabs®-tablets with 4350 ppm F. Each tooth was cut into serial sections and analyzed by polarized light microscopy for assessment of the different zones of white-spot lesions in 3 representative sections. Statistical analysis was based on the Mann-Whitney-Test. Results Both control groups N(- and P(+ exhibited characteristic white-spot lesions. The remineralization and the demineralization inhibition of the lesions increased considerably from N®-2 administration showed partial/total remineralization including lamination and/or disappearance of the body of the lesion. The different results of all 4 groups were statistically highly significant (p Conclusion Based on these results the novel Denttabs® formulation represents a highly effective oral hygiene product and the remineralization is correlated to the fluoride content.

  11. Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

    Directory of Open Access Journals (Sweden)

    Eugenio Picano

    2015-05-01

    Full Text Available A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques—such as vascular, transesophageal, and intravascular ultrasound—on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque, iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque, and markedly hyperechoic with shadowing (calcific plaque. Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging

  12. High-resolution intravascular magnetic resonance quantification of atherosclerotic plaque at 3T

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    Qian Di

    2012-03-01

    Full Text Available Abstract Background The thickness of fibrous caps (FCT of atherosclerotic lesions is a critical factor affecting plaque vulnerability to rupture. This study tests whether 3 Tesla high-resolution intravascular cardiovascular magnetic resonance (CMR employing tiny loopless detectors can identify lesions and accurately measure FCT in human arterial specimens, and whether such an approach is feasible in vivo using animal models. Methods Receive-only 2.2 mm and 0.8 mm diameter intravascular loopless CMR detectors were fabricated for a clinical 3 Tesla MR scanner, and the absolute signal-to-noise ratio determined. The detectors were applied in a two-step protocol comprised of CMR angiography to identify atherosclerotic lesions, followed by high-resolution CMR to characterize FCT, lesion size, and/or vessel wall thickness. The protocol was applied in fresh human iliac and carotid artery specimens in a human-equivalent saline bath. Mean FCT measured by 80 μm intravascular CMR was compared with histology of the same sections. In vivo studies compared aortic wall thickness and plaque size in healthy and hyperlipidemic rabbit models, with post-mortem histology. Results Histology confirmed plaques in human specimens, with calcifications appearing as signal voids. Mean FCT agreed with histological measurements within 13% on average (correlation coefficient, R = 0.98; Bland-Altman analysis, -1.3 ± 68.9 μm. In vivo aortic wall and plaque size measured by 80 μm intravascular CMR agreed with histology. Conclusion Intravascular 3T CMR with loopless detectors can both locate atherosclerotic lesions, and accurately measure FCT at high-resolution in a strategy that appears feasible in vivo. The approach shows promise for quantifying vulnerable plaque for evaluating experimental therapies.

  13. Anti-proliferative effect of extremely low frequency electromagnetic field on preneoplastic lesions formation in the rat liver.

    Science.gov (United States)

    Jiménez-García, Mónica Noemí; Arellanes-Robledo, Jaime; Aparicio-Bautista, Diana Ivette; Rodríguez-Segura, Miguel Angel; Villa-Treviño, Saúl; Godina-Nava, Juan José

    2010-04-24

    Recently, extremely low frequency electromagnetic fields (ELF-EMF) have been studied with great interest due to their possible effects on human health. In this study, we evaluated the effect of 4.5 mT-120 Hz ELF-EMF on the development of preneoplastic lesions in experimental hepatocarcinogenesis. Male Fischer-344 rats were subjected to the modified resistant hepatocyte model and were exposed to 4.5 mT - 120 Hz ELF-EMF. The effects of the ELF-EMF on hepatocarcinogenesis, apoptosis, proliferation and cell cycle progression were evaluated by histochemical, TUNEL assay, caspase 3 levels, immunohistochemical and western blot analyses. The application of the ELF-EMF resulted in a decrease of more than 50% of the number and the area of gamma-glutamyl transpeptidase-positive preneoplastic lesions (P = 0.01 and P = 0.03, respectively) and glutathione S-transferase placental expression (P = 0.01). The number of TUNEL-positive cells and the cleaved caspase 3 levels were unaffected; however, the proliferating cell nuclear antigen, Ki-67, and cyclin D1 expression decreased significantly (P EMF inhibits preneoplastic lesions chemically induced in the rat liver through the reduction of cell proliferation, without altering the apoptosis process.

  14. Anti-proliferative effect of extremely low frequency electromagnetic field on preneoplastic lesions formation in the rat liver

    Directory of Open Access Journals (Sweden)

    Villa-Treviño Saúl

    2010-04-01

    Full Text Available Abstract Background Recently, extremely low frequency electromagnetic fields (ELF-EMF have been studied with great interest due to their possible effects on human health. In this study, we evaluated the effect of 4.5 mT - 120 Hz ELF-EMF on the development of preneoplastic lesions in experimental hepatocarcinogenesis. Methods Male Fischer-344 rats were subjected to the modified resistant hepatocyte model and were exposed to 4.5 mT - 120 Hz ELF-EMF. The effects of the ELF-EMF on hepatocarcinogenesis, apoptosis, proliferation and cell cycle progression were evaluated by histochemical, TUNEL assay, caspase 3 levels, immunohistochemical and western blot analyses. Results The application of the ELF-EMF resulted in a decrease of more than 50% of the number and the area of γ-glutamyl transpeptidase-positive preneoplastic lesions (P = 0.01 and P = 0.03, respectively and glutathione S-transferase placental expression (P = 0.01. The number of TUNEL-positive cells and the cleaved caspase 3 levels were unaffected; however, the proliferating cell nuclear antigen, Ki-67, and cyclin D1 expression decreased significantly (P ≤ 0.03, as compared to the sham-exposure group. Conclusion The application of 4.5 mT - 120 Hz ELF-EMF inhibits preneoplastic lesions chemically induced in the rat liver through the reduction of cell proliferation, without altering the apoptosis process.

  15. Anti-atherosclerotic and anti-inflammatory actions of sesame oil.

    Science.gov (United States)

    Narasimhulu, Chandrakala Aluganti; Selvarajan, Krithika; Litvinov, Dmitry; Parthasarathy, Sampath

    2015-01-01

    Atherosclerosis, a major form of cardiovascular disease, has now been recognized as a chronic inflammatory disease. Nonpharmacological means of treating chronic diseases have gained attention recently. We previously reported that sesame oil has anti-atherosclerotic properties. In this study, we have determined the mechanisms by which sesame oil might modulate atherosclerosis by identifying genes and inflammatory markers. Low-density lipoprotein receptor knockout (LDLR(-/-)) female mice were fed with either an atherogenic diet or an atherogenic diet reformulated with sesame oil (sesame oil diet). Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Plasma samples were used for cytokine analysis. RNA was extracted from the liver tissue and used for global gene arrays. The sesame oil diet significantly reduced atherosclerotic lesions, plasma cholesterol, triglyceride, and LDL cholesterol levels in LDLR(-/-) mice. Plasma inflammatory cytokines, such as MCP-1, RANTES, IL-1α, IL-6, and CXCL-16, were significantly reduced, demonstrating an anti-inflammatory property of sesame oil. Gene array analysis showed that sesame oil induced many genes, including ABCA1, ABCA2, APOE, LCAT, and CYP7A1, which are involved in cholesterol metabolism and reverse cholesterol transport. In conclusion, our studies suggest that a sesame oil-enriched diet could be an effective nonpharmacological treatment for atherosclerosis by controlling inflammation and regulating lipid metabolism.

  16. Anti-Atherosclerotic and Anti-Inflammatory Actions of Sesame Oil

    Science.gov (United States)

    Narasimhulu, Chandrakala Aluganti; Selvarajan, Krithika; Litvinov, Dmitry

    2015-01-01

    Abstract Atherosclerosis, a major form of cardiovascular disease, has now been recognized as a chronic inflammatory disease. Nonpharmacological means of treating chronic diseases have gained attention recently. We previously reported that sesame oil has anti-atherosclerotic properties. In this study, we have determined the mechanisms by which sesame oil might modulate atherosclerosis by identifying genes and inflammatory markers. Low-density lipoprotein receptor knockout (LDLR−/−) female mice were fed with either an atherogenic diet or an atherogenic diet reformulated with sesame oil (sesame oil diet). Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Plasma samples were used for cytokine analysis. RNA was extracted from the liver tissue and used for global gene arrays. The sesame oil diet significantly reduced atherosclerotic lesions, plasma cholesterol, triglyceride, and LDL cholesterol levels in LDLR−/− mice. Plasma inflammatory cytokines, such as MCP-1, RANTES, IL-1α, IL-6, and CXCL-16, were significantly reduced, demonstrating an anti-inflammatory property of sesame oil. Gene array analysis showed that sesame oil induced many genes, including ABCA1, ABCA2, APOE, LCAT, and CYP7A1, which are involved in cholesterol metabolism and reverse cholesterol transport. In conclusion, our studies suggest that a sesame oil-enriched diet could be an effective nonpharmacological treatment for atherosclerosis by controlling inflammation and regulating lipid metabolism. PMID:25562618

  17. Endothelial NLRP3 inflammasome activation and arterial neointima formation associated with acid sphingomyelinase during hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Saisudha Koka

    2017-10-01

    Full Text Available The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM and ceramide associated membrane raft (MR signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto or cholesterol crystal (ChC markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs, as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene. In CAECs with NLRP3 inflammasome formation, membrane raft (MR clustering with NADPH oxidase subunits was found remarkably increased as shown by CTXB (MR marker and gp91phox aggregation indicating the formation of MR redox signaling platforms. This MR clustering was blocked by MR disruptor (MCD, ROS scavenger (Tempol and TXNIP inhibitor (verapamil, accompanied by attenuation of 7-Keto or ChC-induced increase in caspase-1 activity. In animal experiments, Western diet fed mice with partially ligated left carotid artery (PLCA were found to have significantly increased neointimal formation, which was associated with increased NLRP3 inflammasome formation and IL-1β production in the intima of Asm+/+ mice but not in Asm-/- mice. These results suggest that Asm gene and ceramide associated MR clustering are essential to endothelial inflammasome activation and dysfunction in the carotid arteries, ultimately determining the extent of atherosclerotic lesions.

  18. Lymphatic vessels: an emerging actor in atherosclerotic plaque development.

    Science.gov (United States)

    Kutkut, Issa; Meens, Merlijn J; McKee, Thomas A; Bochaton-Piallat, Marie-Luce; Kwak, Brenda R

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease of large- to medium-sized arteries and is the main underlying cause of death worldwide. The lymphatic vasculature is critical for processes that are intimately linked to atherogenesis such as the immune response and cholesterol metabolism. However, whether lymphatic vessels truly contribute to the pathogenesis of atherosclerosis is less clear despite increasing research efforts in this field. PubMed and Ovid MEDLINE databases were searched. In addition, key review articles were screened for relevant original publications. Current knowledge about lymphatic vessels in the arterial wall came from studies that examined the presence and location of such vessels in human atherosclerotic plaque specimens, as well as in a variety of arteries in animal models for atherosclerosis (e.g. rabbits, dogs, rats and mice). Generally, three experimental approaches have been used to investigate the functional role of plaque-associated lymphatic vessels; experimental lymphostasis was used to investigate lymphatic drainage of the arterial wall, and more recently, studies with genetic interventions and/or surgical transplantation have been performed. Lymphatic vessels seem to be mostly present in the adventitial layer of the arterial walls of animals and humans. They are involved in reverse cholesterol transport from atherosclerotic lesions, and arteries with a dense lymphatic network seem naturally protected against atherosclerosis. Lymphangiogenesis is a process that is an important part of the inflammatory loop in atherosclerosis. However, how augmenting or impeding the distribution of lymphatic vessels impacts disease progression remains to be investigated in future studies. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  19. Formation of the main UV-induced thymine dimeric lesions within isolated and cellular DNA as measured by high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Douki, T; Court, M; Sauvaigo, S; Odin, F; Cadet, J

    2000-04-21

    UVB radiation-induced formation of dimeric photoproducts at bipyrimidine sites within DNA has been unambiguously associated with the lethal and mutagenic properties of sunlight. The main lesions include the cyclobutane pyrimidine dimers and the pyrimidine (6-4) pyrimidone adducts. The latter compounds have been shown in model systems to be converted into their Dewar valence isomers upon exposure to UVB light. A new direct assay, based on the use of liquid chromatography coupled to tandem mass spectrometry, is now available to simultaneously detect each of the thymine photoproducts. It was applied to the determination of the yields of formation of the thymine lesions within both isolated and cellular DNA exposed to either UVC or UVB radiation. The cis-syn cyclobutane thymine dimer was found to be the major photoproduct within cellular DNA, whereas the related (6-4) adduct was produced in an approximately 8-fold lower yield. Interestingly, the corresponding Dewar valence isomer could not be detected upon exposure of human cells to biologically relevant doses of UVB radiation.

  20. CD36 Is Significantly Correlated with Adipophilin in Human Carotid Lesions and Inversely Correlated with Plasma ApoAI

    Directory of Open Access Journals (Sweden)

    Sophie Collot-Teixeira

    2008-01-01

    Full Text Available OxLDL uptake and cholesterol efflux inhibition in macrophages play a key role in atherosclerotic plaque formation, rupture, and thrombotic ischemia. This study investigates genes implicated in OxLDL uptake (CD36, SRA, cholesterol efflux inhibition (adipophilin, ADFP, and inflammatory recruitments of leukocytes (IL-8 in plaque lesion areas (PLAs compared to nonplaque lesion areas NPLAs in human carotid endarterectomy specimens. Gene and protein expressions were assayed using quantitative PCR and quantitative immunohistochemistry. Pearson tests were used to investigate potential correlation between (a different gene expressions and (b gene expression and patient's plasma constituents. CD36, SRA, ADFP, and IL-8 were shown to be significantly more expressed in PLA compared to NPLA. In PLA, a significant correlation was observed between CD36, SRA, ADFP, and IL-8 mRNA levels. Moreover, CD36 expression level was significantly inversely correlated to plasma marker ApoAI. The above investigated genes/proteins may play a key role in the maturation of atherosclerotic lesions.

  1. Ghrelin inhibits atherosclerotic plaque angiogenesis and promotes plaque stability in a rabbit atherosclerotic model.

    Science.gov (United States)

    Wang, Li; Chen, Qingwei; Ke, Dazhi; Li, Guiqiong

    2017-04-01

    Intraplaque angiogenesis associates with the instability of atherosclerotic plaques. In the present study, we investigated the effects of ghrelin on intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis. The rabbits were randomly divided into three groups, namely, the control group, atherosclerotic model group, and ghrelin-treated group, with treatments lasting for 4 weeks. We found that the thickness ratio of the intima to media in rabbits of the ghrelin-treated group was significantly lower than that in rabbits of the atherosclerotic model group. The number of neovessels and the levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) decreased dramatically in rabbits of the ghrelin-treated group compared to those of the atherosclerotic model group. Ghrelin significantly decreased the plaque content of macrophages, matrix metalloproteinase (MMP)-2, and MMP-9, in a rabbit model of atherosclerosis. In addition, the level of the pro-inflammatory factor monocyte chemoattractant protein (MCP)-1 was significantly lower in rabbits of the ghrelin-treated group than in rabbits of the atherosclerotic model group. In summary, ghrelin can inhibit intraplaque angiogenesis and promote plaque stability by down-regulating VEGF and VEGFR2 expression, inhibiting the plaque content of macrophages, and reducing MCP-1 expression at an advanced stage of atherosclerosis in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Evaluation of 68Ga-Glutamate Carboxypeptidase II Ligand Positron Emission Tomography for Clinical Molecular Imaging of Atherosclerotic Plaque Neovascularization.

    Science.gov (United States)

    Derlin, Thorsten; Thiele, Johannes; Weiberg, Desiree; Thackeray, James T; Püschel, Klaus; Wester, Hans-Jürgen; Aguirre Dávila, Lukas; Larena-Avellaneda, Axel; Daum, Günter; Bengel, Frank M; Schumacher, Udo

    2016-11-01

    Intraplaque neovascularization contributes to the progression and rupture of atherosclerotic lesions. Glutamate carboxypeptidase II (GCPII) is strongly expressed by endothelial cells of tumor neovasculature and plays a major role in hypoxia-induced neovascularization in rodent models of benign diseases. We hypothesized that GCPII expression may play a role in intraplaque neovascularization and may represent a target for imaging of atherosclerotic lesions. The aim of this study was to determine frequency, pattern, and clinical correlates of vessel wall uptake of a (68)Ga-GCPII ligand for positron emission tomographic imaging. Data from 150 patients undergoing (68)Ga-GCPII ligand positron emission tomography were evaluated. Tracer uptake in various arterial segments was analyzed and was compared with calcified plaque burden, cardiovascular risk factors, and immunohistochemistry of carotid specimens. Focal arterial uptake of (68)Ga-GCPII ligand was identified at 5776 sites in 99.3% of patients. The prevalence of uptake sites was highest in the thoracic aorta; 18.4% of lesions with tracer uptake were colocalized with calcified plaque. High injected dose (P=0.0005) and obesity (P=0.007) were significantly associated with (68)Ga-GCPII ligand accumulation, but other cardiovascular risk factors showed no association. The number of (68)Ga-GCPII ligand uptake sites was significantly associated with overweight condition (P=0.0154). Immunohistochemistry did not show GCPII expression. Autoradiographic blocking studies indicated nonspecific tracer binding. (68)Ga-GCPII ligand positron emission tomography does not identify vascular lesions associated with atherosclerotic risk. Foci of tracer accumulation are likely caused by nonspecific tracer binding and are in part noise-related. Taken together, GCPII may not be a priority target for imaging of atherosclerotic lesions. © 2016 American Heart Association, Inc.

  3. Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression.

    Science.gov (United States)

    Shimizu, Yoichi; Hanzawa, Hiroko; Zhao, Yan; Fukura, Sagiri; Nishijima, Ken-Ichi; Sakamoto, Takeshi; Zhao, Songji; Tamaki, Nagara; Ogawa, Mikako; Kuge, Yuji

    2017-08-01

    Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis. However, IgG accumulates nonspecifically in atherosclerotic regions, and its accumulation mechanisms have not yet been clarified in detail. Therefore, we explored IgG accumulation mechanisms in atherosclerotic lesions and examined images of radiolabeled IgG for the diagnosis of atherosclerosis. Mouse IgG without specificity to biomolecules was labeled with technetium-99m via 6-hydrazinonicotinate to yield [(99m)Tc]IgG. ApoE(-/-) or C57BL/6J mice were injected intravenously with [(99m)Tc]IgG, and their aortas were excised 24 h after injection. After radioactivity measurement, serial aortic sections were autoradiographically and histopathologically examined. RAW264.7 macrophages were polarized into M1 or M2 and then treated with [(99m)Tc]IgG. The radioactivities in the cells were measured after 1 h of incubation. [(99m)Tc]IgG uptake in M1 macrophages was also evaluated after the pretreatment with an anti-Fcγ receptor (FcγR) antibody. The expression levels of FcγRs in the cells were measured by western blot analysis. [(99m)Tc]IgG accumulation levels in the aortas were significantly higher in apoE(-/-) mice than in C57BL/6J mice (5.1 ± 1.4 vs 2.8 ± 0.5 %ID/g, p IgG than M2 or M0 (nonpolarized) macrophages [2.2 ± 0.3 (M1) vs 0.5 ± 0.1 (M2), 0.4 ± 0.1 (M0) %dose/mg protein, p IgG accumulation in M1 macrophages was suppressed by pretreatment with the anti-FcγR antibody [2.2 ± 0.3 (nonpretreatment) vs 1.2 ± 0.2 (pretreatment) %ID/mg protein, p IgG accumulated in pro-inflammatory M1 macrophages via FcγRs in atherosclerotic lesions. Thus, the target biomolecule-independent imaging of active inflammation should be taken into account in the diagnosis of

  4. Brain Lesions

    Science.gov (United States)

    Symptoms Brain lesions By Mayo Clinic Staff A brain lesion is an abnormality seen on a brain-imaging test, such as ... tomography (CT). On CT or MRI scans, brain lesions appear as dark or light spots that don' ...

  5. In Vivo Fluorescence-mediated Tomography Imaging Demonstrates Atorvastatin-mediated Reduction of Lesion Macrophages in ApoE(-/-) Mice

    NARCIS (Netherlands)

    Larmann, Jan; Frenzel, Tim; Schmitz, Martina; Hahnenkamp, Anke; Demmer, Philipp; Immenschuh, Stephan; Tietge, Uwe J. F.; Bremer, Christoph; Theilmeier, Gregor

    Background: Macrophage recruitment into atherosclerotic plaques drives lesion progression, destabilization, and rupture. Chronic statin treatment reduces macrophage plaque content. Information on dynamics of macrophage recruitment would help assessing plaque vulnerability and guiding therapy.

  6. Modifying effect of dietary sesaminol glucosides on the formation of azoxymethane-induced premalignant lesions of rat colon.

    Science.gov (United States)

    Sheng, HongQiang; Hirose, Yoshinobu; Hata, Kazuya; Zheng, Qiao; Kuno, Toshiya; Asano, Nami; Yamada, Yasuhiro; Hara, Akira; Osawa, Toshihiko; Mori, Hideki

    2007-02-08

    Sesame, which has been reported to have preventive effects against various disordered conditions, contains small quantities of lignans and several precursors to them such as sesaminol glucosides (SG). The lignans have the potent antioxidative activity and are suggested to have chemopreventive property. In the present study, we evaluated the modulating effect of SG on the development of colon precancerous lesions, aberrant crypt foci (ACF) and beta-catenin-accumulated crypts (BCAC), in the azoxymethane (AOM)-induced short-term model using male F344 rats. Dietary SG (500 ppm) significantly decreased the incidence of AOM-induced ACF when compared to the control (P<0.01). The incidences of AOM-induced BCAC in the SG-treated groups (250 or 500 ppm) were also significantly lower than that of the control group (P<0.01). Interestingly, administration of 500 ppm SG clearly decreased serum triglyceride level and mRNA expression of intestinal fatty acid-binding protein in the colonic mucosa, as compared to the control. These findings indicate that dietary SG inhibits AOM-induced carcinogenesis and suggest SG as a possible chemopreventive agent.

  7. The presence of some cytokines and Chlamydia pneumoniae in the atherosclerotic carotid plaque in patients with carotid artery stenosis

    Directory of Open Access Journals (Sweden)

    Dariusz Janczak

    2015-02-01

    Full Text Available Background: Over the last few years the role of microorganisms in the pathogenesis of atherosclerosis has been widely discussed. Chlamydia pneumoniae activates immune cells to produce cytokines that are responsible for the formation of atheromatous carotid lesions.Material and methods: The study was carried out at the Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, in 2002-2003, on 100 consecutive symptomatic patients with internal carotid stenosis, who underwent an endarterectomy procedure. Each patient had their carotid artery sampled in order to find C. pneumoniae DNA using the nested PCR method and some cytokines (TGF-β, VEGF, FGF, TNF-α using immunohistochemical examination. The control group consisted of 20 young organ donors who had been diagnosed with brain death and who had their healthy carotid artery harvested. Analogous genetic and immunohistochemical tests were performed.Results: We did not confirm the presence of either cytokines or C. pneumoniae in the healthy carotid arteries. The presence of FGF was probably due to intima fibroblast activity, which is responsible for elastin and collagen synthesis for the extracellular matrix. C. pneumoniae was discovered in 68% of patients with carotid plaques. Three cytokines (TGF-β, FGF, TNF-α were detected in atherosclerotic internal carotid arteries as well.Conclusion: Chronic infection by C. pneumoniae may exacerbate carotid plaque development and may lead to its destabilization.

  8. Involvement of endothelial progenitor cells in the formation of plexiform lesions in broiler chickens: possible role of local immune/inflammatory response.

    Science.gov (United States)

    Tan, Xun; Juan, Fan-Guo; Shah, Ali Q

    Plexiform lesions (PLs), which are often accompanied by perivascular infiltrates of mononuclear cells, represent the hallmark lesions of pulmonary arteries in humans suffering from severe pulmonary arterial hypertension (PAH). Endothelial progenitor cells (EPCs) have been recently implicated in the formation of PLs in human patients. PLs rarely develop in rodent animal models of PAH but can develop spontaneously in broiler chickens. The aim of the present study was to confirm the presence of EPCs in the PLs in broilers. The immune mechanisms involved in EPC dysfunction were also evaluated. Lungs were collected from commercial broilers at 1 to 4 weeks of age. The right/total ventricle ratios indicated normal pulmonary arterial pressures for all sampled birds. Immunohistochemistry was performed to determine the expressions of EPC markers (CD133 and VEGFR-2) and proangiogenic molecule hepatocyte growth factor (HGF) in the lung samples. An EPC/lymphocyte co-culture system was used to investigate the functional changes of EPCs under the challenge of immune cells. PLs with different cellular composition were detected in the lungs of broilers regardless of age, and they were commonly surrounded by moderate to dense perivascular mononuclear cell infiltrates. Immunohistochemical analyses revealed the presence of CD133+ and VEGFR-2+ cells in PLs. These structures also exhibited a strong expression of HGF. Lymphocyte co-culture enhanced EPC apoptosis and completely blocked HGF-stimulated EPC survival and in vitro tube formation. Taken together, this work provides evidence for the involvement of EPCs in the development of PLs in broilers. It is suggested that the local immune cell infiltrate might serve as a contributor to EPC dysfunction by inducing EPC death and limiting their response to angiogenic stimuli. Broiler chickens may be valuable for investigating reversibility of plexogenic arteriopathy using gene-modified inflammation-resistant EPCs.

  9. KLF4 Dependent Phenotypic Modulation of SMCs Plays a Key Role in Atherosclerotic Plaque Pathogenesis

    Science.gov (United States)

    Shankman, Laura S.; Gomez, Delphine; Cherepanova, Olga A.; Salmon, Morgan; Alencar, Gabriel F.; Haskins, Ryan M.; Swiatlowska, Pamela; Newman, Alexandra A. C.; Greene, Elizabeth S.; Straub, Adam C.; Isakson, Brant; Randolph, Gwendalyn J.; Owens, Gary K.

    2015-01-01

    Herein we employ Myh11-CreERT2 ROSA floxed STOP eYFP Apoe−/− smooth muscle cell (SMC) lineage tracing mice to show that traditional methods for detecting SMCs based on immuno-staining fail to detect > 80% of SMC-derived cells within advanced atherosclerotic lesions. These unidentified SMC-derived cells exhibit phenotypes of other cell lineages including macrophages (Mϕs), and mesenchymal stem cells (MSCs). SMC-specific conditional knockout (KO) of Krüppel-like factor 4 (KLF4) resulted in reduced numbers of SMC-derived MSC-, and Mϕ-like cells, marked reductions in lesion size, and increases in multiple indices of plaque stability, including an increase in fibrous cap thickness. Results of in vivo KLF4 ChIP-Seq analyses, and studies in cultured SMC treated with cholesterol identified > 800 KLF4 target genes including many that regulate pro-inflammatory responses of SMC. Results indicate that the contribution of SMCs within atherosclerotic plaques has been greatly underestimated, and that KLF4-dependent transitions in SMC phenotype are critical in lesion pathogenesis. PMID:25985364

  10. Fluorescence imaging of macrophages in atherosclerotic plaques using plasmonic gold nanorose

    Science.gov (United States)

    Wang, Tianyi; Sapozhnikova, Veronika; Mancuso, J. Jacob; Willsey, Brian; Qiu, Jinze; Ma, Li L.; Li, Xiankai; Johnston, Keith P.; Feldman, Marc D.; Milner, Thomas E.

    2011-03-01

    Macrophages are one of the most important cell types involved in the progression of atherosclerosis which can lead to myocardial infarction. To detect macrophages in atherosclerotic plaques, plasmonic gold nanorose is introduced as a nontoxic contrast agent for fluorescence imaging. We report macrophage cell culture and ex vivo tissue studies to visualize macrophages targeted by nanorose using scanning confocal microscopy. Atherosclerotic lesions were created in the aorta of a New Zealand white rabbit model subjected to a high cholesterol diet and double balloon injury. The rabbit was injected with nanoroses coated with dextran. A HeNe laser at 633 nm was used as an excitation light source and a acousto-optical beam splitter was utilized to collect fluorescence emission in 650-760 nm spectral range. Results of scanning confocal microscopy of macrophage cell culture and ex vivo tissue showed that nanoroses produce a strong fluorescence signal. The presence of nanorose in ex vivo tissue was further confirmed by photothermal wave imaging. These results suggest that scanning confocal microscopy can identify the presence and location of nanorose-loaded macrophages in atherosclerotic plaques.

  11. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

    Science.gov (United States)

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  12. Effect of Combined Calcium Hydroxide and Accelerated Portland Cement on Bone Formation and Soft Tissue Healing in Dog Bone Lesions

    Directory of Open Access Journals (Sweden)

    Khorshidi H

    2015-09-01

    Full Text Available Statement of Problem: Recent literatures show that accelerated Portland cement (APC and calcium hydroxide Ca (OH2 may have the potential to promote the bone regeneration. However, certain clinical studies reveal consistency of Ca (OH2, as one of the practical drawbacks of the material when used alone. To overcome such inconvenience, the combination of the Ca (OH2 with a bone replacement material could offer a convenient solution. Objectives: To evaluate the soft tissue healing and bone regeneration in the periodontal intrabony osseous defects using accelerated Portland cement (APC in combination with calcium hydroxide Ca (OH2, as a filling material. Materials and Methods: Five healthy adult mongrel dogs aged 2-3 years old (approximately 20 kg in weight with intact dentition and healthy periodontium were selected for this study. Two one-wall defects in both mesial and distal aspects of the 3rd premolars of both sides of the mandible were created. Therefore, four defects were prepared in each dog. Three defects in each dog were randomly filled with one of the following materials: APC alone, APC mixed with Ca (OH2, and Ca (OH2 alone. The fourth defect was left empty (control. Upon clinical examination of the sutured sites, the amount of dehiscence from the adjacent tooth was measured after two and eight weeks, using a periodontal probe mesiodistally. For histometric analysis, the degree of new bone formation was estimated at the end of the eighth postoperative week, by a differential point-counting method. The percentage of the defect volume occupied by new osteoid or trabecular bone was recorded. Results: Measurement of wound dehiscence during the second week revealed that all five APCs had an exposure of 1-2 mm and at the end of the study all samples showed 3-4 mm exposure across the surface of the graft material, whereas the Ca (OH2, control, and APC + Ca (OH2 groups did not show any exposure at the end of the eighth week of the study. The most

  13. Anti-atherosclerotic activity of catechins depends on their stereoisomerism.

    Science.gov (United States)

    Mika, Magdalena; Kostogrys, Renata B; Franczyk-Żarów, Magdalena; Wikiera, Agnieszka; Maślak, Edyta

    2015-05-01

    In terms of stereochemistry, catechins are divided into two groups: (-) epi forms (2R, 3R) and (-) forms (2S, 3R). Most of the catechins present in green tea are (-) epi forms (2R, 3R). Under the influence of high temperatures, in anaerobic conditions, as a result of epimerization the proportion of the (-) form (2S, 3R) increases. The data indicate that the presence of thermally modified catechins in the diet more efficiently reduces the development of atherosclerosis in apoE knockout mice than the presence of native catechins. The addition of the thermally modified formulations to the high-fat diet resulted in a reduction of the area of atherosclerotic lesions by about 28% (en face method) and 45% (cross-section method) compared to the group fed the high-fat diet without catechins. Furthermore, the body weight gain and plasma TBARS concentration in mice fed a diet with the addition of catechins depends on the degree of epimerization of catechins and decreases with increasing content of catechins belonging to the (-) form (2S, 3R). Moreover, plasma HDL cholesterol concentration in mice depends on catechins' stereoisomerism and increases along with the increasing content of catechins belonging to the (-) form (2S, 3R). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Uptake of 11C-choline in mouse atherosclerotic plaques

    DEFF Research Database (Denmark)

    Laitinen, Iina E K; Luoto, Pauliina; Någren, Kjell

    2010-01-01

    The purpose of this study was to explore the feasibility of (11)C-choline in the assessment of the degree of inflammation in atherosclerotic plaques.......The purpose of this study was to explore the feasibility of (11)C-choline in the assessment of the degree of inflammation in atherosclerotic plaques....

  15. Chlamydia pneumoniae infection enhances microglial activation in atherosclerotic mice.

    NARCIS (Netherlands)

    Voorend, M.; Ven, A.J.A.M. van der; Mulder, M.; Lodder, J.; Steinbusch, H.W.; Bruggeman, C.A.

    2010-01-01

    The presence of Chlamydia pneumoniae in murine brain tissue was studied in atherosclerotic and non-atherosclerotic mice, after peritoneal injection. Furthermore, we investigated whether increased permeability of the blood-brain barrier was implicated in cerebral C. pneumoniae infection and whether

  16. Atherosclerotic carotid plaque assessment with multidetector computed tomography angiography

    NARCIS (Netherlands)

    T.T. de Weert (Thomas)

    2009-01-01

    textabstractThis thesis evaluates the role of MDCT angiography in 1) the depiction of atherosclerotic disease and subsequent luminal stenosis in the arteries that supplies the brain with blood, and 2) the assessment of atherosclerotic plaque features that have been related to plaque vulnerability.

  17. Pregnancy loss and later risk of atherosclerotic disease

    DEFF Research Database (Denmark)

    Ranthe, Mattis Flyvholm; Andersen, Elisabeth Anne Wreford; Wohlfahrt, Jan

    2013-01-01

    Pregnancy losses and atherosclerotic disease may be etiologically linked through underlying pathology. We examined whether miscarriage and stillbirth increase later risk of myocardial infarction, cerebral infarction, and renovascular hypertension.......Pregnancy losses and atherosclerotic disease may be etiologically linked through underlying pathology. We examined whether miscarriage and stillbirth increase later risk of myocardial infarction, cerebral infarction, and renovascular hypertension....

  18. Endovascular treatment of symptomatic intracranial atherosclerotic disease

    Directory of Open Access Journals (Sweden)

    Syed I Hussain

    2011-02-01

    Full Text Available Abstract: Symptomatic intracranial atherosclerotic disease (ICAD is responsible for approximately 10% of all ischemic strokes in the United States. The risk of recurrent stroke may be as high as 35% in patient with critical stenosis greater than 70% in diameter narrowing. Recent advances in medical and endovascular therapy have placed ICAD at the forefront of clinical stroke research to optimize the best medical and endovascular approach to treat this important underlying stroke etiology. Analysis of symptomatic ICAD studies lead to the question that whether angioplasty and or stenting is a safe, suitable and efficacious therapeutic strategy in patients with critical stenoses that are deemed refractory to medical management. Most of the currently available data in support of angioplasty and or stenting in high risk patients with severe symptomatic ICAD is in the form of case series and randomized trial results of endovascular therapy versus medical treatment are awaited. This is a comprehensive review of the state of the art in the endovascular approach with angioplasty and or stenting of symptomatic intracranial atherosclerotic disease.

  19. Blue light-induced retinal lesions, intraretinal vascular leakage and edema formation in the all-cone mouse retina.

    Science.gov (United States)

    Geiger, P; Barben, M; Grimm, C; Samardzija, M

    2015-11-19

    Little is known about the mechanisms underlying macular degenerations, mainly for the scarcity of adequate experimental models to investigate cone cell death. Recently, we generated R91W;Nrl(-/-) double-mutant mice, which display a well-ordered all-cone retina with normal retinal vasculature and a strong photopic function that generates useful vision. Here we exposed R91W;Nrl(-/-) and wild-type (wt) mice to toxic levels of blue light and analyzed their retinas at different time points post illumination (up to 10 days). While exposure of wt mice resulted in massive pyknosis in a focal region of the outer nuclear layer (ONL), the exposure of R91W;Nrl(-/-) mice led to additional cell death detected within the inner nuclear layer. Microglia/macrophage infiltration at the site of injury was more pronounced in the all-cone retina of R91W;Nrl(-/-) than in wt mice. Similarly, vascular leakage was abundant in the inner and outer retina in R91W;Nrl(-/-) mice, whereas it was mild and restricted to the subretinal space in wt mice. This was accompanied by retinal swelling and the appearance of cystoid spaces in both inner and ONLs of R91W;Nrl(-/-) mice indicating edema in affected areas. In addition, basal expression levels of tight junction protein-1 encoding ZO1 were lower in R91W;Nrl(-/-) than in wt retinas. Collectively, our data suggest that exposure of R91W;Nrl(-/-) mice to blue light not only induces cone cell death but also disrupts the inner blood-retinal barrier. Macular edema in humans is a result of diffuse capillary leakage and microaneurysms in the macular region. Blue light exposure of the R91W;Nrl(-/-) mouse could therefore be used to study molecular events preceding edema formation in a cone-rich environment, and thus potentially help to develop treatment strategies for edema-based complications in macular degenerations.

  20. The effect of undissociated acetic-acid concentration of buffer solutions on artificial caries-like lesion formation in human tooth enamel

    NARCIS (Netherlands)

    Groeneveld, A.; Theuns, H.M.; Dijk, J.W.E. van; Driessens, F.C.M.

    1984-01-01

    A chemical system for lesion production was used. The influence on lesion characteristics of the concentration of undissociated acetic acid in a calcium and phosphate-containing buffer solution was investigated. Artificial lesions obtained after demineralization in buffers with a pH of 4.0, 4.5, 5.0

  1. Intracranial Stent Implantation for Drug Resistant Atherosclerotic Stenosis: Results of 52 Cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kuk Seon; Hwang, Dae Hyun; Ko, Young Hwan; Kang, Ik Won; Lee, Eil Seong; Han, You Mie [Dept. of Radiology, Hallym University Hospital Hangang Scared Heart Hospital, Seoul (Korea, Republic of); Kim, In Soo; Hur, Choon Woong [Dept. of Neurosurgery, Myungji St. Mari' s Hospital, Seoul (Korea, Republic of)

    2011-07-15

    We evaluated the usefulness of intracranial stent implantation for treatment of drug resistant atherosclerotic stenoses. Between March 2004 and July 2007, we tried intracranial stent implantation in 49 patients with 52 lesions (anterior circulation 48 cases, posterior circulation 4 cases) who had an ischemic stroke with more than 50% of major cerebral artery stenosis. We classified the lesions by their location and morphology, analyzed the results in terms of the success rate, complication rate, and restenosis rate during the follow-up period. Intracranial stent implantation was performed successfully in 43 cases (82.7%). In eight of the nine cases, the stent implantation failure was due to the tortuosity of the target vessel. There was no major periprocedural complication. One patient showed cerebellar infarction after the procedure. Mean residual stenoses decreased from 70.2% to 13.0%. Four cases (9.3%) demonstrated in-stent restenoses and more than 50% during the mean and 25.3/month after the follow-up period. Success rate of intracranial stent implantation may improve on developing technique and more experience. Low rate of complication and restenosis suggest that we can consider intracranial stent implantation for treatment of drug resistant atherosclerotic stenoses.

  2. Folic acid attenuates homocysteine and enhances antioxidative capacity in atherosclerotic rats.

    Science.gov (United States)

    Cui, Shanshan; Li, Wen; Lv, Xin; Wang, Pengyan; Huang, Guowei; Gao, Yuxia

    2017-10-01

    Atherosclerosis is a chronic disease that can seriously endanger human life. Folic acid supplementation modulates several disorders, including atherosclerosis, via its antiapoptotic and antioxidative properties. This study investigated whether folic acid alleviates atherogenesis by restoring homocysteine levels and antioxidative capacity in atherosclerosis Wistar rats. To this end, 28 Wistar rats were randomly divided into 4 groups (7 rats/group) as follows: (i) wild-type group, fed only the AIN-93 semi-purified rodent diet (folic acid: 2.1 mg/kg); (ii) high-fat + folic acid-deficient group (HF+DEF) (folic acid: 0.2 mg/kg); (iii) high-fat + normal folic acid group (folic acid: 2.1 mg/kg); and (iv) high-fat + folic acid-supplemented group (folic acid: 4.2 mg/kg). After 12 weeks, histopathological changes in the atherosclerotic lesions of the aortic arch were determined. In addition, serum folate levels, plasma homocysteine levels, plasma S-adenosyl-homocysteine levels, antioxidant status, oxidant status, and lipid profiles were evaluated. The results show aggravated atherosclerotic lesions in the HF+DEF group. Folic acid supplementation increased concentrations of serum folate. Further, folic acid supplementation increased high-density lipoprotein-cholesterol, decreased plasma homocysteine levels, and improved antioxidant capacity in atherogenic rats. These findings are consistent with the hypothesis that folic acid alleviates atherogenesis by reducing plasma homocysteine levels and improving antioxidant capacity in rats fed a high-fat diet.

  3. Peripheral atherosclerotic obstructive arteriopathy in Africans ...

    African Journals Online (AJOL)

    Whereas atheromatous lesions are not unknown in Africans, peripheral atheroselerotic occlusive arteriopathy is assumed to be scarce and even almost non existent in some medical minds. From a study spanning 15 years indisputable cases are presented to show that far from being rare the lesion is not uncommon and ...

  4. Ophthalmic masquerades of the atherosclerotic carotids

    Directory of Open Access Journals (Sweden)

    Anupriya Arthur

    2014-01-01

    Full Text Available Patients with carotid atherosclerosis can present with ophthalmic symptoms. These symptoms and signs can be due to retinal emboli, hypoperfusion of the retina and choroid, opening up of collateral channels, or chronic hypoperfusion of the globe (ocular ischemic syndrome. These pathological mechanisms can produce many interesting signs and a careful history can bring out important past symptoms pointing toward the carotid as the source of the patient′s presenting symptom. Such patients are at high risk for an ischemic stroke, especially in the subsequent few days following their first acute symptom. It is important for clinicians to be familiar with these ophthalmic symptoms and signs caused by carotid atherosclerosis for making an early diagnosis and to take appropriate measures to prevent a stroke. This review elaborates the clinical features, importance, and implications of various ophthalmic symptoms and signs resulting from atherosclerotic carotid artery disease.

  5. The gut microbiome in atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Jie, Zhuye; Xia, Huihua; Zhong, Shi-Long

    2017-01-01

    The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals...... with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular......), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform...

  6. Effects of a probiotic soy product and physical exercise on formation of pre-neoplastic lesions in rat colons in a short-term model of carcinogenic

    Directory of Open Access Journals (Sweden)

    Rossi Elizeu A

    2009-08-01

    Full Text Available Abstract Purpose In this study the influence of moderate or intense physical exercise, alone or in combination with the consumption of a soya product fermented with Enterococcus faecium, on the development of colon cancer induced chemically in rats with 1,2-dimethylhydrazine (DMH, was investigated. Methods Eighty male Wistar SPF rats were randomly allocated to 8 groups (n = 10. One week after the start of the program of product ingestion and/or physical activity, all animals except the controls (group I were injected subcutaneously with 50 mg/kg b.w. of 1,2-dimethylhydrazine (DMH. This procedure was repeated at the end of the second week. At the end of the 6-week experiment, all the animals were euthanized; the colons were removed and numbers of ACF was estimated. Results Twenty-four days after the induction of pre-neoplastic lesions, it was evident that the formation of ACF was not significantly reduced by the ingestion of the fermented product, by intense or moderate physical activity or by a combination of these factors, in comparison with the positive control group of rats (p Conclusion The results reported in this article show that consumption of the fermented soy product described here and the practice of physical exercise (intense or moderate were incapable, separately or combined, of inhibiting the formation of ACF in DMH-induced rats. The intense physical exercise led to an increased number of foci in the colons of these rats and, probably, to greater susceptibility to colorectal cancer.

  7. Cross-reacting antibacterial auto-antibodies are produced within coronary atherosclerotic plaques of acute coronary syndrome patients.

    Directory of Open Access Journals (Sweden)

    Filippo Canducci

    Full Text Available Coronary atherosclerosis, the main condition predisposing to acute myocardial infarction, has an inflammatory component caused by stimuli that are yet unknown. We molecularly investigated the nature of the immune response within human coronary lesion in four coronary plaques obtained by endoluminal atherectomy from four patients. We constructed phage-display libraries containing the IgG1/kappa antibody fragments produced by B-lymphocytes present in each plaque. By immunoaffinity, we selected from these libraries a monoclonal antibody, arbitrarily named Fab7816, able to react both with coronary and carotid atherosclerotic tissue samples. We also demonstrated by confocal microscopy that this monoclonal antibody recognized human transgelin type 1, a cytoskeleton protein involved in atherogenesis, and that it co-localized with fibrocyte-like cells transgelin+, CD68+, CD45+ in human sections of coronary and carotid plaques. In vitro fibrocytes obtained by differentiating CD14+ cells isolated from peripheral blood mononuclear cells also interacted with Fab7816, thus supporting the hypothesis of a specific recognition of fibrocytes into the atherosclerotic lesions. Interestingly, the same antibody, cross-reacted with the outer membrane proteins of Proteus mirabilis and Klebsiella pneumoniae (and possibly with homologous proteins of other enterobacteriaceae present in the microbiota. From all the other three libraries, we were able to clone, by immunoaffinity selection, human monoclonal antibodies cross-reacting with bacterial outer membrane proteins and with transgelin. These findings demonstrated that in human atherosclerotic plaques a local cross-reactive immune response takes place.

  8. A salmon protein hydrolysate exerts lipid-independent anti-atherosclerotic activity in ApoE-deficient mice.

    Directory of Open Access Journals (Sweden)

    Cinzia Parolini

    Full Text Available Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo E(-/- mice were divided into two groups and fed a high-fat diet with or without 5% (w/w SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in the 12 apoE(-/- mice fed 5% SPH for 12 weeks compared to the 12 casein-fed control mice. Immunohistochemical characterization of atherosclerotic lesions in aortic sinus displayed no differences in plaque composition between mice fed SPH compared to controls. However, reduced mRNA level of Icam1 in the aortic arch was found. The plasma content of arachidonic acid (C20:4n-6 and oleic acid (C18:1n-9 were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1β, IL-6, TNF-α and GM-CSF, whereas plasma cholesterol and triacylglycerols (TAG were unchanged, accompanied by unchanged mitochondrial fatty acid oxidation and acyl-CoA:cholesterol acyltransferase (ACAT-activity. These data show that a 5% (w/w SPH diet reduces atherosclerosis in apoE(-/- mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids or fatty acids.

  9. Selective ablation of WHHLMI rabbit atherosclerotic plaque by quantum cascade laser in the 5.7 μm wavelength range for less-invasive laser angioplasty

    Science.gov (United States)

    Hashimura, Keisuke; Ishii, Katsunori; Akikusa, Naota; Edamura, Tadataka; Yoshida, Harumasa; Awazu, Kunio

    2013-06-01

    We investigated the potential of a compact and high-power quantum cascade laser (QCL) in the 5.7 μm wavelength range for less-invasive laser angioplasty. Atherosclerotic plaques consist mainly of cholesteryl esters. Radiation at a wavelength of 5.75 μm is strongly absorbed in C=O stretching vibration mode of cholesteryl esters. Our previous study achieved to make cutting differences between a normal artery and an atherosclerotic lesions using nanosecond pulsed laser by difference-frequency generation (DFG laser) at the wavelength of 5.75 μm. For applying this technique to clinical treatment, a compact laser device is required. In this study, QCL irradiation effects to a porcine normal aorta were compared with DFG laser. Subsequently, QCL irradiation effects on an atherosclerotic aorta of myocardial infarction-prone Watanabe heritable hyperlipidemic rabbit (WHHLMI rabbit) and a normal rabbit aorta were observed. As a result, the QCL could make cutting differences between the rabbit atherosclerotic and normal aortas. On the other hand, the QCL induced more thermal damage to porcine normal aorta than the DFG laser at the irradiation condition of comparable ablation depths. In conclusion, the possibility of less-invasive and selective treatment of atherosclerotic plaques using the QCL in the 5.7 μm wavelength range was revealed, although improvement of QCL was required to prevent the thermal damage of a normal artery.

  10. Thermal ablation of WHHLMI rabbit atherosclerotic plaque by quantum cascade laser in the 5.7-μm wavelength range

    Science.gov (United States)

    Hashimura, Keisuke; Ishii, Katsunori; Akikusa, Naota; Edamura, Tadataka; Yoshida, Harumasa; Awazu, Kunio

    2013-03-01

    We evaluated the utility of a compact and high-power quantum cascade laser (QCL) in the 5.7 μm wavelength range for less-invasive laser angioplasty. Atherosclerotic plaques mainly consist of cholesteryl esters. The wavelength of 5.75 μm is well absorbed in C=O stretching vibration mode of cholesteryl esters. Our previous study achieved to make cutting differences between a normal tunica intima of an artery and an atherosclerotic lesions using a nanosecond pulsed laser by difference-frequency generation (DFG laser) at the wavelength of 5.75 μm. For realizing a clinical application of this technique, a compact laser device is required. In this study, QCL irradiation effects to a porcine normal aorta were compared with DFG laser. In addition QCL irradiation effects to an atherosclerotic aorta of myocardial infarction-prone Watanabe heritable hyperlipidemic rabbit (WHHLMI rabbit) and a normal aorta were observed. As a result, the QCL could make cutting difference between the rabbit atherosclerotic aorta and the normal aorta. On the other hand, the QCL induced more thermal damage to porcine normal aorta than the DFG laser at the irradiation condition of comparable ablation depth. In conclusion, the possibility of less-invasive and selective treatment of atherosclerotic plaques using the QCL in the 5.7 μm wavelength range was revealed, although improvement of QCL was required to prevent the thermal damage of a normal artery.

  11. High-Density Lipoprotein Nanoparticle Imaging in Atherosclerotic Vascular Disease

    Directory of Open Access Journals (Sweden)

    Nicholas J. Leeper, MD

    2017-02-01

    Full Text Available Summary: Nanoparticles promise to advance the field of cardiovascular theranostics. However, their sustained and targeted delivery remains an important obstacle. The body synthesizes some “natural” nanoparticles, including high-density lipoprotein (HDL, which may home to the atherosclerotic plaque and promote cholesterol efflux. In a recent article published in JACC: Cardiovascular Imaging, investigators generated modified, radiolabeled HDL nanoparticles and confirmed they accumulated in atherosclerotic lesions from several different species. These approaches hold promise for the noninvasive diagnosis of vulnerable plaque and in the stratification of patients in whom HDL-mimetic therapy may have a clinical benefit. Key Words: atherosclerosis, HDL, imaging, nanoparticles, macrophages/monocytes

  12. Formats

    Directory of Open Access Journals (Sweden)

    Gehmann, Ulrich

    2012-03-01

    Full Text Available In the following, a new conceptual framework for investigating nowadays’ “technical” phenomena shall be introduced, that of formats. The thesis is that processes of formatting account for our recent conditions of life, and will do so in the very next future. It are processes whose foundations have been laid in modernity and which will further unfold for the time being. These processes are embedded in the format of the value chain, a circumstance making them resilient to change. In addition, they are resilient in themselves since forming interconnected systems of reciprocal causal circuits.Which leads to an overall situation that our entire “Lebenswelt” became formatted to an extent we don’t fully realize, even influencing our very percep-tion of it.

  13. In silico analyses of metagenomes from human atherosclerotic plaque samples

    DEFF Research Database (Denmark)

    Mitra, Suparna; Drautz-Moses, Daniela I; Alhede, Morten

    2015-01-01

    a challenge. RESULTS: To investigate microbiome diversity within human atherosclerotic tissue samples, we employed high-throughput metagenomic analysis on: (1) atherosclerotic plaques obtained from a group of patients who underwent endarterectomy due to recent transient cerebral ischemia or stroke. (2......) Presumed stabile atherosclerotic plaques obtained from autopsy from a control group of patients who all died from causes not related to cardiovascular disease. Our data provides evidence that suggest a wide range of microbial agents in atherosclerotic plaques, and an intriguing new observation that shows...... these microbiota displayed differences between symptomatic and asymptomatic plaques as judged from the taxonomic profiles in these two groups of patients. Additionally, functional annotations reveal significant differences in basic metabolic and disease pathway signatures between these groups. CONCLUSIONS: We...

  14. Correlation between aortic/carotid atherosclerotic plaques and cerebral infarction.

    Science.gov (United States)

    Wang, Baojun; Sun, Shaoli; Liu, Guorong; Li, Yuechun; Pang, Jiangxia; Zhang, Jingfen; Yang, Lijuan; Li, Ruiming; Zhang, Hui; Jiang, Changchun; Li, Xiue

    2013-08-01

    The aim of this study was to investigate the correlation between aortic/carotid atherosclerotic plaques and cerebral infarction. We examined 116 cases of cerebral infarction using transcranial Doppler ultrasound in order to exclude cerebrovascular stenosis. Transesophageal echocardiography and color Doppler ultrasound were used to detect aortic atherosclerotic plaques (AAPs) and carotid atherosclerotic plaques (CAPs). AAPs were detected in a total of 70 of the 116 cases (60.3%), including 56 with moderate/severe atherosclerotic changes (48.3%). The difference in the incidence of various types of infarction between APP severity levels was significant (PCAPs (55.2%), including 46 with unstable plaque (39.7%). The difference in the incidence of various types of infarction between CAP stability levels was significant (PCAP are significant causes of embolic infarction without stenosis in the internal carotid arteries.

  15. Differential effects of daily-moderate versus weekend-binge alcohol consumption on atherosclerotic plaque development in mice.

    Science.gov (United States)

    Liu, Weimin; Redmond, Eileen M; Morrow, David; Cullen, John P

    2011-12-01

    We examined the effect of daily-moderate (2 drinks/day, 7 days/week) and weekend-binge (7 drinks/day, 2 days/week) patterns of alcohol consumption on plasma lipid levels and physiological parameters of atherosclerotic plaque development. ApoE k/o mouse were fed (1) 'daily-moderate' (blood alcohol content: 0.07%) or (2) 'weekend-binge' (blood alcohol content: 0.23%), or (3) an isocaloric cornstarch mix. Then, to induce atherosclerotic plaque formation, all groups underwent partial carotid artery ligation, started on an atherogenic diet and continued on the alcohol feeding regimen. After 2 weeks plasma lipid levels and atherosclerotic plaque formation were assessed. While there was an increase in HDL-C levels in both binge and moderate groups, LDL-C levels were significantly decreased in the daily-moderate drinking mice and significantly elevated in the weekend-binge drinking mice. In the daily-moderate alcohol group there was a decrease in atherosclerotic plaque volume, concomitant with an increase in lumen volume and decreased macrophage accumulation, when compared to no alcohol mice. In contrast, after 4 weeks of weekend-binge alcohol there was an increase in plaque volume, concomitant with a decrease in lumen volume and increased deposition of macrophages. These findings demonstrate for the first time a differential effect of daily-moderate vs. weekend-binge alcohol consumption on atherosclerotic plaque development and highlight the importance of patterns of alcohol consumption, as opposed to total amount consumed, in relation to the cardiovascular effects of alcohol. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Modeling of Experimental Atherosclerotic Plaque Delamination.

    Science.gov (United States)

    Leng, Xiaochang; Chen, Xin; Deng, Xiaomin; Sutton, Michael A; Lessner, Susan M

    2015-12-01

    A cohesive zone model (CZM) approach is applied to simulate atherosclerotic plaque delamination experiments in mouse abdominal aorta specimens. A three-dimensional finite element model is developed for the experiments. The aortic wall is treated as a fiber-reinforced, highly deformable, incompressible material, and the Holzapfel-Gasser-Ogden (HGO) model is adopted for the aortic bulk material behavior. Cohesive elements are placed along the plaque-media interface along which delamination occurs. The 3D specimen geometry is created based on images from the experiments and certain simplifying approximations. A set of HGO and CZM parameter values is determined based on values suggested in the literature and through matching simulation predictions of the load vs. load-point displacement curve with experimental measurements for one loading-delamination-unloading cycle. Using this set of parameter values, simulation predictions for four other loading-delamination-unloading cycles are obtained, which show good agreement with experimental measurements. The findings of the current study demonstrate the applicability of the CZM approach in arterial tissue failure simulations.

  17. Safrole-2',3'-oxide induces atherosclerotic plaque vulnerability in apolipoprotein E-knockout mice.

    Science.gov (United States)

    Su, Le; Zhang, Haiyan; Zhao, Jing; Zhang, Shangli; Zhang, Yun; Zhao, Baoxiang; Miao, Junying

    2013-02-27

    Safrole-2',3'-oxide (SFO) is the major electrophilic metabolite of safrole (4-allyl-1, 2-methylenedioxybenzene), a natural plant constituent found in essential oils of numerous edible herbs and spices and in food containing these herbs, such as pesto sauce, cola beverages and bologna sausages. The effects of SFO in mammalian systems, especially the cardiovascular system, are little known. Disruption of vulnerable atherosclerotic plaques in atherosclerosis, a chronic inflammatory disease, is the main cause of cardiovascular events. In this study, we investigated SFO-induced atherosclerotic plaque vulnerability (possibility of rupture) in apolipoprotein E-knockout (apoE(-/-)) mice. Lipid area in vessel wall reached 59.8% in high dose SFO (SFO-HD) treated group, which is only 31.2% in control group. SFO treatment changed the lesion composition to an unstable phenotype, increased the number of apoptotic cells in plaque and the endothelium in plaques was damaged after SFO treatment. Furthermore, compared with control groups, the plaque endothelium level of p75(NTR) was 3-fold increased and the liver level of p75(NTR) was 17.4-fold increased by SFO-HD. Meanwhile, the serum level of KC (a functional homolog of IL-8 and the main proinflammatory alpha chemokine in mice) in apoE(-/-) mice was up to 357pg/ml in SFO-HD treated group. Thus, SFO contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating p75(NTR) and IL-8 and cell apoptosis in plaque. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Effect of sexual steroids on the calcium content of aortic atherosclerotic plaque of oophorectomized rabbits

    Directory of Open Access Journals (Sweden)

    J.M. Aldrighi

    2005-05-01

    Full Text Available We determined the effect of conjugated equine estrogen plus medroxyprogesterone acetate on calcium content of aortic atherosclerotic lesions in oophorectomized adult New Zealand rabbits submitted to a cholesterol rich diet. Five groups of 10 animals each were studied: G1 = control, G2 = cholesterol diet only, G3 = diet plus conjugated equine estrogen (0.625 mg/day; G4 and G5 = diet, conjugated equine estrogen (0.625 mg/day plus medroxyprogesterone acetate (5 and 10 mg/day, respectively. Mean weight varied from 2.7 ± 0.27 to 3.1 ± 0.20 kg (P = 0.38 between groups at the beginning and 3.1 ± 0.27 to 3.5 ± 0.20 kg (P = 0.35 at the end of the experiment. Cholesterol and triglyceride levels were determined at the time of oophorectomy, 21 days after surgery (time 0, and at the end of follow-up of 90 days. The planimetric method was used to measure plaque and caryometric method for histopathologic examination of the aorta. Calcium content was determined by the method of von Kossa. A similar increase in cholesterol occurred in all treated groups without differences between them at the end of the study. Groups G4 and G5 had smaller areas of atherosclerotic lesions (2.33 ± 2.8 and 2.45 ± 2.1 cm², respectively than the groups receiving no progestogens (G2: 5.6 ± 4 and G3: 4.6 ± 2.8 cm²; P = 0.02. The relation between lesion area and total aorta area was smaller in groups treated with combined drugs compared to the groups receiving no progesterone (G4: 14.9 ± 13 and G5: 14.2 ± 13.4 vs G2: 35.8 ± 26 and G3: 25 ± 8 cm², respectively; P = 0.017. Oral conjugated equine estrogen (0.625 mg/day plus medroxyprogesterone acetate (5 or 10 mg/day provoked a greater reduction in atherosclerotic plaque area and calcium content in treated groups, suggesting a dose-dependent effect.

  19. Electromyographic identification of spinal oscillator patterns and recouplings in a patient with incomplete spinal cord lesion: oscillator formation training as a method to improve motor activities.

    Science.gov (United States)

    Schalow, G; Blanc, Y; Jeltsch, W; Zäch, G A

    1996-08-01

    A patient with a strongly lesioned spinal cord, sub C5, relearned running, besides improving other movements, by an oscillator formation training (rhythmic, dynamic, stereotyped exercise). After 45 days of jumping on a springboard and other rhythm trainings, the patient was able to run 90 m in 41 s (7.9 km/h) (even 9.3 km/h 3 years after the lesion) besides marching (5.7 km/h), cycling, playing tennis and skiing. FF-type (alpha 1) (f = 8.3-11.4 Hz) and FR-type (alpha 2) (f = 6.7 Hz) motor unit firings were identified by electromyography (EMG) with surface electrodes by their oscillatory firing patterns in this patient. In EMG literature, the alpha 2-oscillatory firing is called "myokymic discharging". Alternating long and short oscillation periods were measured in FF-type motor units, with changing focus (change from long/short to short/long oscillation periods). The alternating mean period durations differed by approximately 10 ms. Transient synchronization of oscillatory firing FF-type motor units was observed with up to two phase relations per oscillation cycle. In recumbent position, the phase change in synchronization of two oscillatory firing motor units in the soleus muscle of one leg correlated with the change from alternating to symmetrical oscillatory firing of a third motor unit in the soleus muscle of the other leg. This measurement indicates that the alternating oscillatory firing of premotor neuronal networks is correlated with synchronization of oscillatory firing neuronal subnetworks, i.e., with coupling changes of oscillators, and is not due to reciprocal inhibition of half-centre oscillators as suggested by the change from alternating to symmetrical oscillatory firing. Coupling changes of oscillatory firing subnetworks to generate macroscopic (integrative) network functions are therefore a general organization form of the central nervous system (CNS), and are not related to rhythmic movements like walking or running only. It is proposed that

  20. Serial changes of coronary atherosclerotic plaque: Assessment with 64-slice multi-detector computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Young; Kang, Doo Kyoung; Sun, Joo Sung; Choi, So Yeon [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2013-12-15

    Evaluate the progression of coronary atherosclerotic plaque during follow-up, and its association with cardiovascular risk factors. Fifty-six atherosclerotic patients with plaque were enrolled in this retrospective study. Patient's plaque was detected on repeat 64-slice multidetector CT scans with a mean interval of 25 ± 10 months changes in calcified and non-calcified plaque volumes and cardiovascular risk factors were assessed over time. Absolute and relative changes in plaque volume were compared, and the association between rapid progression and cardiovascular risk factors was determined. Diameter of the stenosis, length, calcified and non-calcified lesion plaque volumes increased significantly on follow-up CT. Absolute and relative annual changes in plaque volumes were significantly greater in non-calcified plaque (median, 22.7 mm{sup 3}, 90.4%) than in calcified plaque (median, 0.7 mm{sup 3}, 0%). Obesity, smoking, hypertension, hypercholesterolemia, and low high-density lipoprotein were significant predictors of progression of non-calcified plaque. Progression of calcified plaque was not associated with any cardiovascular risk factors. Coronary plaque volume increased significantly on follow-up CT. The rate of progression is related to non-calcified plaque than to calcified plaque. Cardiovascular risk factors are independently associated with the rapid progression of non-calcified plaque volume, but not associated with the progression of calcified plaque.

  1. Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques

    Directory of Open Access Journals (Sweden)

    Elisabetta Zinellu

    2012-01-01

    Full Text Available Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS. The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% (P<0.01 in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability.

  2. Lesiones laborales

    OpenAIRE

    Plachesi, Pierina

    2015-01-01

    Las lesiones laborales se producen por un esfuerzo repetitivo, cuando un exceso de presión se ejerce sobre una parte del cuerpo provocando lesiones óseas, articulares, musculares y daños en los tejidos. Los accidentes laborales también pueden producir una lesión en el organismo y esto sumado a diversos factores es un problema para la reinserción laboral de los trabajadores de la energía eléctrica. Objetivo: Establecer cuáles son las lesiones más frecuentes que afectan a los ...

  3. Atherosclerotic plaque rupture: local or systemic process?

    NARCIS (Netherlands)

    Lutgens, Esther; van Suylen, Robert-Jan; Faber, Birgit C.; Gijbels, Marion J.; Eurlings, Petra M.; Bijnens, Ann-Pascale; Cleutjens, Kitty B.; Heeneman, Sylvia; Daemen, Mat J. A. P.

    2003-01-01

    It is generally established that the unstable plaque is the major cause of acute clinical sequelae of atherosclerosis. Unfortunately, terms indicating lesions prone to plaque instability, such as "vulnerable plaque," and the different phenotypes of unstable plaques, such as plaque rupture, plaque

  4. (18)F-FDG imaging of human atherosclerotic carotid plaques reflects gene expression of the key hypoxia marker HIF-1α

    DEFF Research Database (Denmark)

    Pedersen, Sune Folke; Græbe, Martin; Hag, Anne Mette F

    2013-01-01

    To investigate the association between gene expression of key molecular markers of hypoxia and inflammation in atherosclerotic carotid lesions with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) uptake as determined clinically by positron emission tomography (PET). Studies using PET have demonstra......To investigate the association between gene expression of key molecular markers of hypoxia and inflammation in atherosclerotic carotid lesions with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) uptake as determined clinically by positron emission tomography (PET). Studies using PET have...... between hypoxia and glucose metabolism in vivo. The marker of inflammation CD68 is also associated with (18)F-FDG-uptake (SUVmax). As CD68 and HIF-1α gene expression co-variate their information is overlapping....

  5. Association of postalimentary lipemia with atherosclerotic manifestations

    Directory of Open Access Journals (Sweden)

    J. Tentor

    2012-11-01

    Full Text Available We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA, insulin, cholesteryl ester transfer protein (CETP, autoantibodies to epitopes of oxidized LDL (oxLDL Ab, lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT was determined by Doppler ultrasound. The volunteers were classified into early (N = 39 and late (N = 31 triacylglycerol (TAG responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period by CETP (negative and FFA (positive. This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.

  6. Open surgery for atherosclerotic chronic mesenteric ischemia.

    Science.gov (United States)

    Kruger, Allan J; Walker, Philip J; Foster, Wallace J; Jenkins, Jason S; Boyne, Nicholas S; Jenkins, Julie

    2007-11-01

    This study was undertaken to document the results of our current practice of open mesenteric revascularization to enable comparison with the recent trend of percutaneous endovascular therapy for the treatment of chronic mesenteric ischemia. Patients were identified via operation code data as well ongoing audit data from 1992 until 2006. Only patients with a history of chronic mesenteric ischemia secondary to atherosclerosis for 3 months or longer were included in the study. Follow-up data have been collected prospectively and include clinical examination and history, as well as graft surveillance consisting of mesenteric duplex ultrasonography, computed tomography, and/or angiography every 6 months for 3 years and then yearly thereafter. Thirty-nine consecutive patients underwent 41 open revascularization procedures for chronic mesenteric ischemia, comprising 67 bypass grafts. The mean patient age was 65 years (range, 45-85 years), and 44% (n = 17) were male. Symptoms were present on average for 11 months (range, 4-48 months) before treatment. The average weight loss was 11.4 kg, and three patients (7.6%) also had evidence of ischemic enteritis. There was one perioperative death, thus giving a perioperative mortality rate of 2.5%. Perioperative morbidity occurred in five patients (12.2%). Primary graft patency was 92% at 5 years. Seven patients died during follow-up, which ranged from 4 to 161 months (mean, 39 months)-one (2.5%) from mesenteric ischemia. Two (5%) other patients have had recurrent mesenteric ischemic symptoms. Open surgical mesenteric revascularization by bypass grafting for atherosclerotic-induced chronic mesenteric ischemia can be performed with low mortality and morbidity and provides excellent long-term primary patency rates and symptom-free outcomes. Pending more data on the acute and long-term results of endovascular techniques, open mesenteric revascularization remains the gold standard for most patients with chronic mesenteric ischemia.

  7. Association of postalimentary lipemia with atherosclerotic manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Tentor, J. [Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Nakamura, R.T. [Laboratório de Diagnóstico por Imagem, Campinas, SP (Brazil); Departamento de Radiologia, Universidade Estadual de Campinas, Campinas, SP (Brazil); Gidlund, M. [Laboratório de Imunofisiopatologia, Instituto de Ciências Biológicas, Universidade de São Paulo, São Paulo, SP (Brazil); Barros-Mazon, S. [Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Harada, L.M. [Laboratório de Lípides, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Zago, V.S.; Oba, J.F.; Faria, E.C. de [Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2012-08-10

    We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m{sup 2} body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.

  8. Hibiscus sabdariffa leaf polyphenolic extract inhibits LDL oxidation and foam cell formation involving up-regulation of LXRα/ABCA1 pathway.

    Science.gov (United States)

    Chen, Jing-Hsien; Wang, Chau-Jong; Wang, Chi-Ping; Sheu, Jenn-Yuan; Lin, Chia-Liang; Lin, Hui-Hsuan

    2013-11-01

    The oxidative modification of low-density lipoprotein (LDL) is involved in the pathogenesis of atherosclerotic lesions through the formation of macrophage-derived foam cells. In the present study, we aimed to investigate the anti-atherosclerotic effect of Hibiscus sabdariffa leaf polyphenolic extract (HLP), which is rich in flavonoid. The inhibitory effect of HLP on oxidation and lipid peroxidation of LDL was defined in vitro. HLP showed potential in reducing foam cell formation and intracellular lipid accumulation in oxidised-LDL (ox-LDL)-induced macrophage J774A.1 cells under non-cytotoxic concentrations. Molecular data showed these influences of HLP might be mediated via liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) pathway, as demonstrated by the transfection of LXRα siRNA. Our data implied that HLP up-regulated the LXRα/ABCA1 pathway, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that HLP potentially could be developed as an anti-atherosclerotic agent. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Pregnancy associated plasma protein-A (PAPP-A) is not a marker of the vulnerable atherosclerotic plaque.

    Science.gov (United States)

    Iversen, Kasper; Teisner, Ane; Dalager, Soren; Olsen, Karen Ege; Floridon, Charlotte; Teisner, Børge

    2011-03-01

    To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A. Vulnerable plaques and control tissues were examined by immunohistochemistry. Volunteers and patients with non-atherosclerotic disease were examined for release of PAPP-A during ischemia and medical treatment. Non-atherosclerotic tissue samples were examined after incubation with heparins. We were not able to detect PAPP-A in vulnerable plaques. Patients and volunteers experiencing ischemic events without atherosclerotic lesions only had elevated PAPP-A when treated with heparin. When tissue from normal artery wall was incubated with heparin, PAPP-A was eluted. This was not the case for non-arterial tissue samples. Elevation of PAPP-A in patients with acute coronary syndromes seems to be caused by heparin induced release of PAPP-A from the arterial wall and not due to excretion from vulnerable plaques. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  10. Review: Mechanical Characterization of Carotid Arteries and Atherosclerotic Plaques.

    Science.gov (United States)

    de Korte, Chris L; Fekkes, Stein; Nederveen, Aart J; Manniesing, Rashindra; Hansen, Hendrik Rik H G

    2016-10-01

    Cardiovascular disease (CVD) is a leading cause of death and is in the majority of cases due to the formation of atherosclerotic plaques in arteries. Initially, thickening of the inner layer of the arterial wall occurs. Continuation of this process leads to plaque formation. The risk of a plaque to rupture and thus to induce an ischemic event is directly related to its composition. Consequently, characterization of the plaque composition and its proneness to rupture are of crucial importance for risk assessment and treatment strategies. The carotid is an excellent artery to be imaged with ultrasound because of its superficial position. In this review, ultrasound-based methods for characterizing the mechanical properties of the carotid wall and atherosclerotic plaque are discussed. Using conventional echography, the intima media thickness (IMT) can be quantified. There is a wealth of studies describing the relation between IMT and the risk for myocardial infarction and stroke. Also the carotid distensibility can be quantified with ultrasound, providing a surrogate marker for the cross-sectional mechanical properties. Although all these parameters are associated with CVD, they do not easily translate to individual patient risk. Another technique is pulse wave velocity (PWV) assessment, which measures the propagation of the pressure pulse over the arterial bed. PWV has proven to be a marker for global arterial stiffness. Recently, an ultrasound-based method to estimate the local PWV has been introduced, but the clinical effectiveness still needs to be established. Other techniques focus on characterization of plaques. With ultrasound elastography, the strain in the plaque due to the pulsatile pressure can be quantified. This technique was initially developed using intravascular catheters to image coronaries, but recently noninvasive methods were successfully developed. A high correlation between the measured strain and the risk for rupture was established. Acoustic

  11. Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs

    DEFF Research Database (Denmark)

    Jacobsen, Kevin; Lund, Marie Bek; Shim, Jeong

    2017-01-01

    Fibrous cap smooth muscle cells (SMCs) protect atherosclerotic lesions from rupturing and causing thrombosis, while other plaque SMCs may have detrimental roles in plaque development. To gain insight into recruitment of different plaque SMCs, we mapped their clonal architecture in aggregation...... of either eGFP+ or nonfluorescent SMCs, indicating substantial clonal expansion of a few cells. Similarly, plaques in mice with SMC-restricted Confetti expression showed oligoclonal SMC populations with little intermixing between the progeny of different medial SMCs. Phenotypes comprised both ACTA2+ SMCs...... in the cap and heterogeneous ACTA2– SMCs in the plaque interior, including chondrocyte-like cells and cells with intracellular lipid and crystalline material. Fibrous cap SMCs were invariably arranged in endothelium-aligned clonal sheets, confirming results in the aggregation chimeras. Analysis of the clonal...

  12. The Role of Perivascular Adipose Tissue in Non-atherosclerotic Vascular Disease

    Directory of Open Access Journals (Sweden)

    Tetsuo Horimatsu

    2017-11-01

    Full Text Available Perivascular adipose tissue (PVAT surrounds most large blood vessels and plays an important role in vascular homeostasis. PVAT releases various chemokines and adipocytokines, functioning in an endocrine and paracrine manner to regulate vascular signaling and inflammation. Mounting evidence suggests that PVAT plays an important role in atherosclerosis and hypertension; however, the role of PVAT in non-atherosclerotic vascular diseases, including neointimal formation, aortic aneurysm, arterial stiffness and vasculitis, has received far less attention. Increasing evidence suggests that PVAT responds to mechanical endovascular injury and regulates the subsequent formation of neointima via factors that promote smooth muscle cell growth, adventitial inflammation and neovascularization. Circumstantial evidence also links PVAT to the pathogenesis of aortic aneurysms and vasculitic syndromes, such as Takayasu's arteritis, where infiltration and migration of inflammatory cells from PVAT into the vascular wall may play a contributory role. Moreover, in obesity, PVAT has been implicated to promote stiffness of elastic arteries via the production of reactive oxygen species. This review will discuss the growing body of data and mechanisms linking PVAT to the pathogenesis of non-atherosclerotic vascular diseases in experimental animal models and in humans.

  13. Virtual histology study of atherosclerotic plaque composition in patients with stable angina and acute phase of acute coronary syndromes without ST segment elevation

    Directory of Open Access Journals (Sweden)

    Ivanović Miloš

    2013-01-01

    Full Text Available Introduction. Rupture of vulnerable atherosclerotic plaques is the cause of most acute coronary syndromes (ACS. Postmortem studies which compared stable coronary lesions and atherosclerotic plaques in patients who have died because of ACS indicated high lipid-core content as one of the major determinants of plaque vulnerability. Objective. Our primary goal was to assess the potential relations of plaque composition determined by IVUS-VH (Intravascular Ultrasound - Virtual Histology in patients with stable angina and subjects in acute phase of ACS without ST segment elevation. Methods. The study comprised of 40 patients who underwent preintervention IVUS examination. Tissue maps were reconstructed from radio frequency data using IVUS-VH software. Results. We analyzed 53 lesions in 40 patients. Stable angina was diagnosed in 24 patients (29 lesions, while acute phase of ACS without ST elevation was diagnosed in 16 patients (24 lesions. In the patients in acute phase of ACS without ST segment elevation IVUS-VH examination showed a significantly larger area of the necrotic core at the site of minimal lumen area and a larger mean of the necrotic core volume in the entire lesion comparing to stable angina subjects (1.84±0.90 mm2 vs. 0.96±0.69 mm2; p<0.001 and 20.94±15.79 mm3 vs. 11.54±14.15 mm3; p<0.05 respectively. Conclusion. IVUS-VH detected that the necrotic core was significantly larger in atherosclerotic lesions in patients in acute phase of ACS without ST elevation comparing to the stable angina subjects and that it could be considered as a marker of plaque vulnerability.

  14. L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE(-/-) transgenic mice expressing CETP.

    Science.gov (United States)

    Collins, Heidi L; Drazul-Schrader, Denise; Sulpizio, Anthony C; Koster, Paul D; Williamson, Yuping; Adelman, Steven J; Owen, Kevin; Sanli, Toran; Bellamine, Aouatef

    2016-01-01

    Dietary l-carnitine can be metabolized by intestinal microbiota to trimethylamine, which is absorbed by the gut and further oxidized to trimethylamine N-oxide (TMAO) in the liver. TMAO plasma levels have been associated with atherosclerosis development in ApoE(-/-) mice. To better understand the mechanisms behind this association, we conducted in vitro and in vivo studies looking at the effect of TMAO on different steps of atherosclerotic disease progression. J774 mouse macrophage cells were used to evaluate the effect of TMAO on foam cell formation. Male ApoE(-/-) mice transfected with human cholesteryl ester transfer protein (hCETP) were fed l-carnitine and/or methimazole, a flavin monooxygenase 3 (FMO3) inhibitor that prevents the formation of TMAO. Following 12 week treatment, l-carnitine and TMAO plasma levels, aortic lesion development, and lipid profiles were determined. TMAO at concentrations up to 10-fold the Cmax reported in humans did not affect in vitro foam cell formation. In ApoE(-/-)mice expressing hCETP, high doses of l-carnitine resulted in a significant increase in plasma TMAO levels. Surprisingly, and independently from treatment group, TMAO levels inversely correlated with aortic lesion size in both aortic root and thoracic aorta. High TMAO levels were found to significantly correlate with smaller aortic lesion area. Plasma lipid and lipoprotein levels did not change with treatment nor with TMAO levels, suggesting that the observed effects on lesion area were independent from lipid changes. These findings suggest that TMAO slows aortic lesion formation in this mouse model and may have a protective effect against atherosclerosis development in humans. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. [Comparative study on the viscoelastic properties of phagocytes of atherosclerotic origin].

    Science.gov (United States)

    Zeng, Wei; Deng, Xiaoyan; Qin, Jian

    2009-12-01

    A micropipette aspiration technique was adopted in this study on the viscoelastic properties of phagocytes of atherosclerotic origin. A standard linear solid model (Kelvin model) was employed to fit the experimental data, and the 3 viscoelastic coefficients of the model were used to compare the mechanical properties of the phagocytes in different phases during atherosclerosis development. The experimental results indicated that prior to the formation of atherosclerosis, the deformability of the macrophages matured from monocytes decreased, and their rigidity increased. At the initial stage of atherosclerosis formation, the deformability of the foam-cells decreased further. We believe that the deterioration in the deformability of the cells might reduce their mobility within the arterial wall, thus leading to the genesis of atherosclerosis caused by the stagnation and accumulation of the cells laden with atherogenic lipids within the arterial wall. This finding may have important implication in the researches on arteriosclerosis.

  16. ATHEROSCLEROTIC CARDIOVASCULAR DISEASE IN OLDER ADULTS WITH DIABETES MELLITUS

    Science.gov (United States)

    Barzilay, Joshua I.; Mukamal, Kenneth J.; Kizer, Jorge R.

    2014-01-01

    Diabetes Mellitus exerts a strong effect on atherosclerotic cardiovascular disease risk into older age (beyond ages 70 to 74 years). This effect is particularly noticeable with regard to coronary artery disease and cerebral microvascular disease. Thus Diabetes Mellitus in older age deserves the same careful medical attention as it does in middle age. PMID:25453299

  17. Cryotherapy increases features of plaque stability in atherosclerotic rabbits.

    Science.gov (United States)

    Verheye, Stefan; Roth, Lynn; De Meyer, Inge; Van Hove, Cor E; Nahon, Daniel; Santoianni, Domenic; Yianni, John; Martinet, Wim; Buchbinder, Maurice; De Meyer, Guido R Y

    2016-08-20

    In the last 10 years, cryotherapy has been investigated as a new technology to treat vascular disease. The efficiency of cryotherapy in stabilising atherosclerotic plaques has never been described. The purpose of the present study was to evaluate the effect of catheter-based cryotherapy on atherosclerotic plaque composition in a rabbit model of atherosclerosis. Twenty-four New Zealand white rabbits were fed a 0.3% cholesterol-supplemented diet for 24 weeks. At two predefined sites of the atherosclerotic thoracic aorta, catheter-based cryotherapy, applying either single-dose, double-dose cryotherapy or control inflation, was performed after randomisation. Rabbits were continued on a cholesterol-supplemented diet for one day (acute) or four weeks (chronic). One day after cryotherapy, apoptotic cell death of smooth muscle cells (SMCs) and endothelial cells (ECs) was observed, whereas macrophages were unaffected. Four weeks later, the amount of SMCs was restored, the EC layer was regenerated, and a subendothelial macrophage-free layer was formed, indicative of a more stable plaque. In addition, both the thickness and the type I collagen content of the fibrous cap were increased. The present study demonstrated that cryotherapy is feasible and appears to stabilise atherosclerotic plaques in a rabbit model.

  18. Atherosclerotic changes of vessels caused by restriction of movement

    Science.gov (United States)

    Gvishiani, G. S.; Kobakhidze, N. G.; Mchedlishvili, M. G.; Dekanosidze, T. I.

    1980-01-01

    The effect of restriction of movement on the development of atheroscelerosis was studied in rabbits. Drastic restriction of movement for 20 and 30 days causes atherosclerotic alterations of the aorta and shifts in ECG which are characteristic of coronary atherosclerosis. At the same time, shortening of the duration of blood coagulation and an increase in the content of catecholamines and beta-lipoproteids occur.

  19. Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral vascular disease.

    LENUS (Irish Health Repository)

    Saeed, A

    2012-01-31

    Atherosclerotic peripheral vascular disease is a common presenting cause for digital ischaemia in life long smokers. Acute severe Type II Cryoglobulinaemic vasculitis is a rare yet important cause, which may present with similar clinical features and which if undiagnosed may be rapidly fatal. Following the instigation of therapy with intravenous methylprednisolone and cyclophosphamide this patient made an excellent recovery.

  20. Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression

    NARCIS (Netherlands)

    Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

    AIMS: Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte

  1. Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile.

    Science.gov (United States)

    Merghani, Ahmed; Maestrini, Viviana; Rosmini, Stefania; Cox, Andrew T; Dhutia, Harshil; Bastiaenan, Rachel; David, Sarojini; Yeo, Tee Joo; Narain, Rajay; Malhotra, Aneil; Papadakis, Michael; Wilson, Mathew G; Tome, Maite; AlFakih, Khaled; Moon, James C; Sharma, Sanjay

    2017-07-11

    Studies in middle-age and older (masters) athletes with atherosclerotic risk factors for coronary artery disease report higher coronary artery calcium (CAC) scores compared with sedentary individuals. Few studies have assessed the prevalence of coronary artery disease in masters athletes with a low atherosclerotic risk profile. We assessed 152 masters athletes 54.4±8.5 years of age (70% male) and 92 controls of similar age, sex, and low Framingham 10-year coronary artery disease risk scores with an echocardiogram, exercise stress test, computerized tomographic coronary angiogram, and cardiovascular magnetic resonance imaging with late gadolinium enhancement and a 24-hour Holter. Athletes had participated in endurance exercise for an average of 31±12.6 years. The majority (77%) were runners, with a median of 13 marathon runs per athlete. Most athletes (60%) and controls (63%) had a normal CAC score. Male athletes had a higher prevalence of atherosclerotic plaques of any luminal irregularity (44.3% versus 22.2%; P=0.009) compared with sedentary males, and only male athletes showed a CAC ≥300 Agatston units (11.3%) and a luminal stenosis ≥50% (7.5%). Male athletes demonstrated predominantly calcific plaques (72.7%), whereas sedentary males showed predominantly mixed morphology plaques (61.5%). The number of years of training was the only independent variable associated with increased risk of CAC >70th percentile for age or luminal stenosis ≥50% in male athletes (odds ratio, 1.08; 95% confidence interval, 1.01-1.15; P=0.016); 15 (14%) male athletes but none of the controls revealed late gadolinium enhancement on cardiovascular magnetic resonance imaging. Of these athletes, 7 had a pattern consistent with previous myocardial infarction, including 3(42%) with a luminal stenosis ≥50% in the corresponding artery. Most lifelong masters endurance athletes with a low atherosclerotic risk profile have normal CAC scores. Male athletes are more likely to have a CAC

  2. Atherosclerotic burden in coronary and peripheral arteries in patients with first clinical manifestation of coronary artery disease.

    Science.gov (United States)

    Kranjec, Igor

    2011-04-01

    The aim of our study was to assess the atherosclerotic burden in patients with the first symptoms of coronary artery disease (CAD). The study population consisted of 100 consecutive patients (new-onset severe angina or myocardial infarction) and 70 age and sex matched asymptomatic volunteers. Functional and morphologic atherosclerotic markers were sought in carotid, brachial and femoral arteries of all individuals by means of high-resolution ultrasonography, whereas coronary arteriography was performed in the CAD patients only. A total of 347 coronary lesions [230 (66%) obstructive] were discovered in the CAD patients as well as 105 peripheral plaques [26 (25%) obstructive]. The mean percentage diameter stenosis of the culprit coronary lesion was 83.8 ± 15.8%, the mean vessel score 1.7 (range 0-3), the mean stenosis score 19.8 (range 1.5-89.0), and the mean extent score 49.1% (range 10-65%). Endothelium-dependent vasodilation, as assessed by the brachial flow-mediated response (FMR), was reduced by 50% in the CAD patients (P peripheral arteries of the CAD patients (P arteries of the CAD patients by 43%, in brachial arteries by 20% and in femoral arteries by 57% (P peripheral arteries of our patients with the first clinical presentation of CAD.

  3. Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

    Directory of Open Access Journals (Sweden)

    M.H.L.P. Souza

    2003-10-01

    Full Text Available Gastric antral dysmotility has been implicated in the pathogenesis of indomethacin-induced gastric damage, but the relationship between gastric motor abnormalities and mucosal lesions has not been extensively studied. We investigated whether changes in gastric tone and gastric retention correlate with mucosal lesions and neutrophil migration in indomethacin-induced gastric damage in rats. Indomethacin, either 5 or 20 mg/kg (INDO-5 and INDO-20, was instilled into the stomach, and then gastric damage, neutrophil migration, gastric tone and gastric retention were assessed 1 or 3 h later. Gastric damage was calculated as the sum of the lengths of all mucosal lesions, and neutrophil migration was measured by assaying myeloperoxidase activity. Gastric tone was determined by a plethysmometric method, and gastric retention of either saline or Sustacal® was evaluated by a scintigraphic method. Gastric damage was detectable 3 h after either INDO-5 or INDO-20, but not after 1 h. Neutrophil migration was significantly higher 3 h after INDO-20 as compared with INDO-5 or control group, but not after 1 h. Values of gastric tone 1 and 3 h after either INDO-5 (1 h = 1.73 ± 0.07 ml; 3 h = 1.87 ± 0.03 ml or INDO-20 (1 h = 1.70 ± 0.02 ml; 3 h = 1.79 ± 0.03 ml were significantly lower than in controls (1 h = 1.48 ± 0.05 ml; 3 h = 1.60 ± 0.06 ml. Gastric retention of saline was higher 1 h after INDO-5 (58.9 ± 3.3% or INDO-20 (56.1 ± 3.1% compared to control (45.5 ± 1.7%, but not after 3 h. There were no differences concerning gastric retention of Sustacal® between the various groups. Indomethacin induced decreased gastric tone and delayed gastric emptying, which precede mucosal lesion and neutrophil infiltration. These results indicate that there is no relationship between these gastric motor abnormalities and mucosal lesion in indomethacin-induced gastropathy.

  4. CT Determination of Fractional Flow Reserve in Coronary Lesions

    Directory of Open Access Journals (Sweden)

    Mester András

    2016-12-01

    Full Text Available Invasively determined fractional flow reserve (FFR represents the gold-standard method for the functional evaluation of coronary lesions. Coronary computed tomography angiography (CCTA provides characterization of the coronary anatomy, with important morphological information on the atherosclerotic plaques, but does not offer a hemodynamic evaluation of coronary artery lesions. CT evaluation of FFR (FFRCT is a new noninvasive diagnostic method, which provides anatomical and functional assessment of the whole coronary tree, based on computational techniques, with no more radiation or hyperemic agent administration compared with routine CCTA. Recent studies demonstrated the safety and accuracy of FFRCT and its therapeutic use and cost benefits in real-world clinical use.

  5. Vascular brain lesions, brain atrophy, and cognitive decline. The Second Manifestations of ARTerial diseased-Magnetic Resonance (SMART-MR) study

    NARCIS (Netherlands)

    Kooistra, M.; Geerlings, M.I.; van der Graaf, Y.; Mali, W.P.T.M.; Vincken, K.L.; Kappelle, L.J.; Muller, M.; Biessels, G.J.

    2014-01-01

    We examined the association between brain atrophy and vascular brain lesions (i.e., white matter lesions [WMLs] or brain infarcts), alone or in combination, with decline in memory and executive functioning over 4 years of follow-up in 448 patients (57 ± 9.5 years) with symptomatic atherosclerotic

  6. Classification of atherosclerotic and non-atherosclerotic individuals using multiclass state vector machine.

    Science.gov (United States)

    Kumar, Paulraj Ranjith; Priya, Mohan

    2014-01-01

    Coronary artery disease due to atherosclerosis is an epidemic in India. An estimated 1.3 million Indians died from this in 2000. The projected death from coronary artery disease by 2016 is 2.98 million. To build an effective model which assorts the individuals, whether they belong to the normal group, risk group and pathologic group regarding atherosclerosis in real time by doing necessary preprocessing techniques and to compare the performance with other state-of-the-art machine learning techniques. In this work we have employed STULONG dataset. We have made a deep case study in selecting the attributes which contributes for higher accuracy in predicting the target. The selected attributes includes missing values. Initially our work includes imputation of missing values using Iterative Principal Component Analysis (IPCA). The second step includes selecting best features using Fast Correlation Based Filter (FCBF). Finally the classifier Multiclass Support Vector Machine (SVM) with kernel Radial Basis Function (RBF) is used for classification of atherosclerotic community. For the subjects belonging to the classes of normal, risk and pathologic, our methodology has outperformed with an accuracy of 99.85%, 99.80% and 99.46% respectively. The combined optimization methods such as Iterative Principal Component Analysis (IPCA) for missing value imputation, Multiclass SVM for classifying normal, risk and pathologic community in real time has performed with overall accuracy of about 98.97%. The essential pre-processing technique, Fast Correlation Based Filter (FCBF) was employed to further intensifying the target.

  7. Anomalous origin of the right coronary artery from the pulmonary artery: an autopsied sudden death case with severe atherosclerotic disease of the left coronary artery.

    Science.gov (United States)

    Nagai, T; Mukai, T; Takahashi, S; Takada, A; Saito, K; Harada, K; Mori, S; Abe, N

    2014-03-01

    Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare anomaly. It may contribute to myocardial ischemia or sudden death, although the lesion is usually asymptomatic. We report a sudden death case of a 58-year-old man with ARCAPA coexisting with severe atherosclerotic coronary artery disease. He had been healthy until he complained of chest pain, several days before death, despite the discovery of heart murmur in childhood and suspicion of valvular heart disease. The autopsy revealed not only typical findings of the right coronary anomaly with well-developed collateral circulations but also severe atherosclerotic lesions of the left coronary artery, and ischemic change of the myocardium in the left and right coronary arterial perfusion territory. In addition to the "coronary steal" phenomenon primarily caused by ARCAPA, the reduced flow of both coronary arteries and further increase of "coronary steal" due to atherosclerotic obstructive coronary disease might have contributed to the patient's death. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice

    Directory of Open Access Journals (Sweden)

    Zhao Yarui

    2011-01-01

    Full Text Available Abstract Background Sphingomyelin synthase 2 (SMS2 contributes to de novo sphingomyelin (SM biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis. Methods The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR and protein level examination (SMS activity assay. Result We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2 or GFP cDNA (AdV-GFP. On day six after intravenous infusion of 2 × 1011 particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p Conclusions Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis.

  9. Endothelial lipase is highly expressed in macrophages in advanced human atherosclerotic lesions

    DEFF Research Database (Denmark)

    Bartels, Emil D; Nielsen, John E; Lindegaard, Marie Louise Skakkebæk

    2007-01-01

    on sections of carotid endarterectomy specimens from patients with symptomatic cerebrovascular disease. In each of eight patients, EL mRNA and/or protein were seen in areas between the necrotic core and the fibrotic cap where they colocalized with LPL and macrophage-specific CD68. Moreover...

  10. BCG lowers plasma cholesterol levels and delays atherosclerotic lesion progression in mice

    NARCIS (Netherlands)

    van Dam, Andrea D.; Bekkering, Siroon; Crasborn, Malou; van Beek, Lianne; van den Berg, Susan M.; Vrieling, Frank; Joosten, Simone A.; van Harmelen, Vanessa; de Winther, Menno P. J.; Lütjohann, Dieter; Lutgens, Esther; Boon, Mariëtte R.; Riksen, Niels P.; Rensen, Patrick C. N.; Berbée, Jimmy F. P.

    2016-01-01

    Bacille-Calmette-Guérin (BCG), prepared from attenuated live Mycobacterium bovis, modulates atherosclerosis development as currently explained by immunomodulatory mechanisms. However, whether BCG is pro- or anti-atherogenic remains inconclusive as the effect of BCG on cholesterol metabolism, the

  11. BCG lowers plasma cholesterol levels and delays atherosclerotic lesion progression in mice

    NARCIS (Netherlands)

    Dam, A.D. van; Bekkering, S.; Crasborn, M.; Beek, L. van der; Berg, S.M. van den; Vrieling, F.; Joosten, S.A.; Harmelen, V. van; Winther, M.P. de; Lutjohann, D.; Lutgens, E.; Boon, M.R.; Riksen, N.P.; Rensen, P.C.; Berbee, J.F.

    2016-01-01

    BACKGROUND AND AIMS: Bacille-Calmette-Guerin (BCG), prepared from attenuated live Mycobacterium bovis, modulates atherosclerosis development as currently explained by immunomodulatory mechanisms. However, whether BCG is pro- or anti-atherogenic remains inconclusive as the effect of BCG on

  12. Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice.

    Directory of Open Access Journals (Sweden)

    Martine Bot

    Full Text Available AIMS: Altered sphingosine 1-phosphate (S1P homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/- deficiency on leukocyte subsets relevant to atherosclerosis. METHODS AND RESULTS: LDL receptor deficient mice that were transplanted with Sgpl1(-/- bone marrow showed disrupted S1P gradients translating into lymphopenia and abrogated lymphocyte mitogenic and cytokine response as compared to controls. Remarkably however, Sgpl1(-/- chimeras displayed mild monocytosis, due to impeded stromal retention and myelopoiesis, and plasma cytokine and macrophage expression patterns, that were largely compatible with classical macrophage activation. Collectively these two phenotypic features of Sgpl1 deficiency culminated in diminished atherogenic response. CONCLUSIONS: Here we not only firmly establish the critical role of hematopoietic S1P lyase in controlling S1P levels and T cell trafficking in blood and lymphoid tissue, but also identify leukocyte Sgpl1 as critical factor in monocyte macrophage differentiation and function. Its, partly counterbalancing, pro- and anti-inflammatory activity spectrum imply that intervention in S1P lyase function in inflammatory disorders such as atherosclerosis should be considered with caution.

  13. Chemokines in atherosclerotic lesion development and stability : from mice to man

    NARCIS (Netherlands)

    Jager, Saskia Christel Antoinette de

    2008-01-01

    Cardiovascular diseases are the major cause of morbidity and mortality in western societies. The most common clinical manifestations are stroke and acute myocardial infarction and in both ailments atherosclerosis is the underlying culprit. Atherosclerosis is a lipid-mediated chronic inflammatory

  14. Lack of myeloid Fatp1 increases atherosclerotic lesion size in Ldlr-/- mice

    Science.gov (United States)

    Altered metabolism is an important regulator of macrophage (MF) phenotype, which contributes to inflammatory diseases such as atherosclerosis. Broadly, pro-inflammatory, classically-activated MFs (CAM) are glycolytic while alternatively-activated MFs (AAM) oxidize fatty acids, although there is prof...

  15. Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

    National Research Council Canada - National Science Library

    Marco Aurélio Lumertz Saffi Mariana Vargas Furtado Carisi Anne Polanczyk Márlon Munhoz Montenegro Ingrid Webb Josephson Ribeiro Cassio Kampits Alex Nogueira Haas Cassiano Kuchenbecker R?sing Eneida Rejane Rabelo-Silva

    2015-01-01

    .... Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease...

  16. Community-based statins and advanced carotid plaque: Role of CD163 positive macrophages in lipoprotein-associated phospholipase A2 activity in atherosclerotic plaque.

    Science.gov (United States)

    Otsuka, Fumiyuki; Zhao, XiaoQing; Trout, Hugh H; Qiao, Ye; Wasserman, Bruce A; Nakano, Masataka; Macphee, Colin H; Brandt, Martin; Krug-Gourley, Sue; Guo, Liang; Ladich, Elena R; Cheng, Qi; Davis, Harry R; Finn, Aloke V; Virmani, Renu; Kolodgie, Frank D

    2017-12-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzymatic inflammatory biomarker primarily bound to low-density lipoprotein cholesterol, is associated with an approximate twofold increased risk of cardiovascular disease and stroke. Despite indications that circulating Lp-PLA2 is sensitive to statins, it remains largely unknown whether statin usage exerts local effects on Lp-PLA2 expression at the site of atheromatous plaque. Carotid plaques (n = 38) were prospectively collected from symptomatic (n = 18) and asymptomatic (n = 20) patients with (n = 20) or without (n = 18) documented statin history. In all cases, endarterectomy was performed where the primary stenosis was removed in an undisturbed manner. Serial cryosections of the presenting lesion were assessed histologically for macrophages, Lp-PLA2, and cell death (apoptotic index). Symptomatic lesions exhibited less calcification, with greater inflammation characterized by increased expression of CD68+ and CD163+ macrophage subsets, and Lp-PLA2. Symptomatic plaques also exhibited greater necrotic core area and increased apoptosis, as compared with asymptomatic lesions. In contrast, statin treatment did not appear to influence any of these parameters, except for the extent of apoptosis, which was less in statin treated as compared with statin naïve lesions. Overall, Lp-PLA2 expression correlated positively with necrotic core area, CD68+ and CD163+ macrophage area, and cell death. Finally, in vitro assays and dual immunofluorescence staining confirmed CD163-expressing monocytes/macrophages are also a major source of Lp-PLA2. Statin treatment has no effect on local atherosclerotic lesion Lp-PLA2 activity, therefore, the addition of anti-inflammatory treatments to further decrease macrophage Lp-PLA2 expression in atherosclerotic lesions may reduce lesional inflammation and cell death, and prevent necrotic core expansion and lesion progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Cigarette smoking and cardio-renal events in patients with atherosclerotic renal artery stenosis.

    Directory of Open Access Journals (Sweden)

    Christopher A Drummond

    Full Text Available Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731 clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931 were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001. In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD. Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001. Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01 whereas creatinine and estimated glomerular filtration rate (eGFR were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.

  18. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque.

    Science.gov (United States)

    Goel, Sunny; Miller, Avraham; Agarwal, Chirag; Zakin, Elina; Acholonu, Michael; Gidwani, Umesh; Sharma, Abhishek; Kulbak, Guy; Shani, Jacob; Chen, On

    2015-01-01

    Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level.

  19. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    Directory of Open Access Journals (Sweden)

    Sunny Goel

    2015-01-01

    Full Text Available Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level.

  20. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

    DEFF Research Database (Denmark)

    Bowman, Louise; Hopewell, Jemma C; Chen, Fang

    2017-01-01

    BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol...... vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per...... was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin...

  1. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    OpenAIRE

    Goel, Sunny; Miller, Avraham; Agarwal, Chirag; Zakin, Elina; Acholonu, Michael; Gidwani, Umesh; Sharma, Abhishek; Kulbak, Guy; Shani, Jacob; Chen, On

    2015-01-01

    Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstabl...

  2. A Review on Atherosclerotic Biology, Wall Stiffness, Physics of Elasticity, and Its Ultrasound-Based Measurement.

    Science.gov (United States)

    Patel, Anoop K; Suri, Harman S; Singh, Jaskaran; Kumar, Dinesh; Shafique, Shoaib; Nicolaides, Andrew; Jain, Sanjay K; Saba, Luca; Gupta, Ajay; Laird, John R; Giannopoulos, Argiris; Suri, Jasjit S

    2016-12-01

    Functional and structural changes in the common carotid artery are biomarkers for cardiovascular risk. Current methods for measuring functional changes include pulse wave velocity, compliance, distensibility, strain, stress, stiffness, and elasticity derived from arterial waveforms. The review is focused on the ultrasound-based carotid artery elasticity and stiffness measurements covering the physics of elasticity and linking it to biological evolution of arterial stiffness. The paper also presents evolution of plaque with a focus on the pathophysiologic cascade leading to arterial hardening. Using the concept of strain, and image-based elasticity, the paper then reviews the lumen diameter and carotid intima-media thickness measurements in combined temporal and spatial domains. Finally, the review presents the factors which influence the understanding of atherosclerotic disease formation and cardiovascular risk including arterial stiffness, tissue morphological characteristics, and image-based elasticity measurement.

  3. Uniaxial tensile testing approaches for characterisation of atherosclerotic plaques.

    Science.gov (United States)

    Walsh, M T; Cunnane, E M; Mulvihill, J J; Akyildiz, A C; Gijsen, F J H; Holzapfel, G A

    2014-03-03

    The pathological changes associated with the development of atherosclerotic plaques within arterial vessels result in significant alterations to the mechanical properties of the diseased arterial wall. There are several methods available to characterise the mechanical behaviour of atherosclerotic plaque tissue, and it is the aim of this paper to review the use of uniaxial mechanical testing. In the case of atherosclerotic plaques, there are nine studies that employ uniaxial testing to characterise mechanical behaviour. A primary concern regarding this limited cohort of published studies is the wide range of testing techniques that are employed. These differing techniques have resulted in a large variance in the reported data making comparison of the mechanical behaviour of plaques from different vasculatures, and even the same vasculature, difficult and sometimes impossible. In order to address this issue, this paper proposes a more standardised protocol for uniaxial testing of diseased arterial tissue that allows for better comparisons and firmer conclusions to be drawn between studies. To develop such a protocol, this paper reviews the acquisition and storage of the tissue, the testing approaches, the post-processing techniques and the stress-strain measures employed by each of the nine studies. Future trends are also outlined to establish the role that uniaxial testing can play in the future of arterial plaque mechanical characterisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Amputation of extremity in patients with atherosclerotic gangrene

    Directory of Open Access Journals (Sweden)

    Tsareva Yu.O.

    2011-12-01

    Full Text Available Aim of investigation — to analyze the results of treatment of patients with atherosclerotic gangrene of a limb, to identify the causes of adverse outcomes amputation. Materials and methods: We analyzed the results of examination and treatment of 218 patients with atherosclerotic gangrene of the limb. Good outcome of amputation was considered the primary surgical wound healing of the stump. Suppuration, secondary healing, re-amputation and death we attributed to the adverse results of amputation. Results: The adverse outcomes of amputation due to technical errors in surgery, properly chosen level, inadequate drainage of the wound stump, an unsuccessful operation on the arteries of a limb, inadequate empirical antibiotic therapy, patient's age, functional capabilities of myocardium, the duration of critical ischemia, as well as the lack of psychological adaptation of patients before amputation. Conclusion: To decide the need for amputation in patients with atherosclerotic gangrene follows the assessment of possible vascular reconstructive surgery. In determining the level of amputation is necessary to objectively assess the degree of disruption of regional blood flow using multilevel manometry and laser Dopplerflowmetry. In preparation for amputation should be paid special attention to the correction of rheological and coagulation properties of blood, normalization of the functional state of the myocardium, as well as specialized psychotherapeutic training for timely and adequate psychological adaptation of the patient

  5. Lipocalin (LCN 2 Mediates Pro-Atherosclerotic Processes and Is Elevated in Patients with Coronary Artery Disease.

    Directory of Open Access Journals (Sweden)

    Raghav Oberoi

    Full Text Available Lipocalin (LCN 2 is associated with multiple acute and chronic inflammatory diseases but the underlying molecular and cellular mechanisms remain unclear. Here, we investigated whether LCN2 is released from macrophages and contributes to pro-atherosclerotic processes and whether LCN2 plasma levels are associated with the severity of coronary artery disease progression in humans.In an autocrine-paracrine loop, tumor necrosis factor (TNF-α promoted the release of LCN2 from murine bone-marrow derived macrophages (BMDM and vice versa. Moreover, LCN2 stimulation of BMDM led to up-regulation of M1 macrophage markers. In addition, enhanced migration of monocytic J774A.1 cells towards LCN2 was observed. Furthermore, LCN2 increased the expression of the scavenger receptors Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1 as well as scavenger receptor class A-1 (SRA-1 and induced the conversion of macrophages to foam cells. In atherosclerotic lesions of low density lipoprotein receptor-deficient (ldlr-/- mice fed a high fat, high cholesterol diet, LCN2 was found to be co-localized with macrophages in the shoulder region of the atherosclerotic plaque. In addition, LCN2 plasma levels were significantly increased in plasma samples of these mice. Finally, LCN2 plasma levels correlated with the severity of coronary artery disease (CAD in patients as determined by coronary angiography.Here we demonstrated that LCN2 plays a pivotal role in processes involved in atherogenesis by promoting polarization and migration of monocytic cells and development of macrophages towards foam cells. Moreover, LCN2 may be used as a prognostic marker to determine the status of CAD progression.

  6. [Screening strategies for the diagnosis of asymptomatic arterial lesions in patients with atherothrombosis].

    Science.gov (United States)

    Varenne, O; Touzé, E; Collet, J P; Raoux, F; Boissier, C; Carpentier, P H; Alpérovitch, A; Mas, J L; Montalescot, G

    2005-10-01

    Atherosclerosis is a ubiquitous inflammatory disease. Patients presenting an acute atherothrombotic event (acute coronary syndrom, stroke, aortic aneurysm, ...) have an increased risk of events in remote arterial territories affected by atherosclerosis. These patients could benefit from systematic screening of asymptomatic atherosclerotic lesions to avoid these complications. For each atherosclerotic territory (coronary artery, carotid artery, aorta, peripheral arteries including renal arteries), we review the methods for screening asymptomatic atherothrombotic lesions which could justify specific treatments: coronary artery stenosis > or = 50%, carotid artery stenosis > or = 60%, renal artery stenosis > or = 50%, and abdominal aortic aneurysm > or = 30 mm. This review shows that non invasive methods (ie, echography, tomodensitometry) are widely available for diagnosis of asymptomatic lesions in carotid and renal arteries, and in the aorta. Despite its invasive caracteristic, coronarory angiography remains the gold-standard for the diagnosis of coronary artery disease. However, cardiac multi-slices CT-scan appears a promising technique for asymptomatic patients.

  7. Dynamic MRI of orbital lesions

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Akihiro; Matsumoto, Hiroko (Kochi Medical School, Nangoku (Japan))

    1991-04-01

    Study of time intensity curves was performed for 15 orbital lesions. Inflammatory lesions (2 chronic dacryoadenitis, 1 chalazion, 1 inflammatory pseudotumor), 1 meningioma, and 4 pseudolymphoma showed rapid increase with run off. They showed peak formations within 2 minutes. Tumors except for meningioma (3 malignant lymphoma, 2 retinoblastoma, 1 pleomorphic adenoma of lacrimal gland) showed gradual increase without peak formation. No difference between benign and malignancy was detected. Dynamic MRI would be useful for differential diagnosis between pseudotumor and malignant lymphoma, that has been difficult for imaging diagnosis so far. (author).

  8. Links between atherosclerotic and periodontal disease.

    Science.gov (United States)

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-02-01

    Periodontal disease (PD) and cardiovascular disease (CVD) are highly prevalent in the modern community. Both pathologies are chronic inflammatory disorders, which are influenced by multiple risk factors. In part, these factors such as age, smoking, and diabetes overlap between PD and CVD. Epidemiological studies suggest that PD is strongly associated with increased CVD risk. Biochemical and physiological analyses involving in vitro experiments, animal models, and clinical studies provided evidence for the substantial impact of periodontal pathogens, their virulence factors, and bacterial endotoxins on all general pathogenic CVD mechanisms such as endothelial dysfunction, systemic inflammation, oxidative stress, foam cell formation, lipid accumulation, vascular remodeling, and atherothrombosis. Interventional studies showed moderate beneficial effects of PD treatment on reducing systemic inflammation and endothelial dysfunction. However, no interventional studies were performed to assess whether periodontal therapy can primarily prevent CVD. In summary, current data suggest for a strong contributory role of periodontal infection to CVD but cannot provide sufficient evidence for a role of PD as a cause for cardiovascular pathology. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. High-Resolution magnetic resonance imaging of carotid atherosclerotic plaque; Hochaufloesende Bildgebung atherosklerotischer Gefaesswandlaesionen der Karotiden durch die Magnetresonanztomografie

    Energy Technology Data Exchange (ETDEWEB)

    Saam, T.; Reiser, M.; Nikolaou, K. [Inst. fuer Klinische Radiologie, Ludwig-Maximilians-Univ. Muenchen (Germany); Schoenberg, S.O. [Inst. fuer Klinische Radiologie, Klinikum Mannheim gGmbH, Universitaetsklinikum Medizinische Fakultaet Mannheim (Germany); Hatsukami, T.S. [Surgery, VA Puget Sound Health Care System and Univ. of Washington (United States); Yuan, C. [Radiology, Univ. of Washington (United States)

    2008-02-15

    Stroke is the third most common cause of mortality in the United States with an incidence rate of approximately 700 000 deaths per year. As a means to prevent cerebrovascular events, current concepts advocate endarterectomy or carotid stenting in patients with advanced carotid disease. Arterial stenosis alone has been shown to be a poor predictor of cardiovascular events and therefore both arterial stenosis and patient symptom status are taken as indications for interventional therapy. Several studies have shown that symptomatic subjects benefit more from a carotid endarterectomy than asymptomatic subjects: 3 - 6 carotid endarterectomies are needed to prevent one stroke per year in symptomatic subjects with > 70% stenosis compared to 14 - 17 carotid endarterectomies in asymptomatic patients with > 50% stenosis. It is commonly accepted today that factors other than the degree of luminal stenosis can determine a patient's symptom status, such as the composition or the superficial structure of atherosclerotic plaque. High-resolution magnetic resonance imaging has overcome the limitations of current angiographic techniques and has emerged as a leading non-invasive imaging modality for atherosclerotic disease, especially within carotid arteries and other large vessels. In this review, the state of the art in MRI of atherosclerosis is presented in terms of hardware and image acquisition protocols. Also, the results of validation studies for measuring lesion size, composition and inflammation will be summarized. Finally, the status of several clinical trials involving MRI of atherosclerosis will be reviewed. (orig.)

  10. Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Johan L M Björkegren

    2014-02-01

    Full Text Available Plasma cholesterol lowering (PCL slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80% and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr(-/-Apob (100/100 Mttp (flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions.

  11. Hematopoietic arginase 1 deficiency results in decreased leukocytosis and increased foam cell formation but does not affect atherosclerosis.

    Science.gov (United States)

    Ren, Baoyan; Van Kampen, Erik; Van Berkel, Theo J C; Cruickshank, Sheena M; Van Eck, Miranda

    2017-01-01

    Arginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages. In endothelial cells, conversely, NO is strongly anti-atherogenic. However, until now, the role of Arg1 in atherosclerosis is largely unknown. The aim of this study is to specifically investigate the effect of Arg1 deletion in hematopoietic cells on atherosclerosis susceptibility. Ldlr KO mice were transplanted with Arg1(flox/flox);Tie2-Cre (Arg1 KO) bone marrow (BM) or wildtype (WT) BM. After 8 weeks of recovery on chow diet, recipients mice were fed a Western-Type Diet (WTD) for 10 weeks to induce atherosclerosis. After 10-week WTD challenge, blood leukocyte counts were decreased by 25% (p atherosclerosis could be demonstrated, indicating that hematopoietic Arg1 function is not a decisive factor in atherosclerotic plaque formation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Renal Artery Stenting in Patients With Documented Resistant Hypertension and Atherosclerotic Renal Artery Stenosis (ANDORRA)

    Science.gov (United States)

    2018-01-24

    Hypertension; Hypertension Resistant to Conventional Therapy; Angiographically Proven Grade III Unilateral or Bilateral Atherosclerotic Renal Artery Stenosis (ARAS) Greater Than or Equal to 60 Percent

  13. {sup 18}F-FDG PET and intravascular ultrasonography (IVUS) images compared with histology of atherosclerotic plaques: {sup 18}F-FDG accumulates in foamy macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Ishino, Seigo [Takeda Pharmaceutical Company Limited, Pharmaceutical Research Division, Fujisawa (Japan); Takeda Pharmaceutical Company Limited, Biomolecular Research Laboratories, Pharmaceutical Research Division, Fujisawa, Kanagawa (Japan); Ogawa, Mikako; Magata, Yasuhiro [Hamamatsu University School of Medicine, Medical Photonics Research Center, Hamamatsu (Japan); Mori, Ikuo; Nishimura, Satoshi; Ikeda, Shota; Sugita, Taku; Oikawa, Tatsuo; Horiguchi, Takashi [Takeda Pharmaceutical Company Limited, Pharmaceutical Research Division, Fujisawa (Japan)

    2014-04-15

    Intravascular ultrasonography (IVUS) and {sup 18}F-FDG PET have been used to evaluate the efficacy of antiatherosclerosis drugs. These two modalities image different characteristics of atherosclerotic plaques, and a comparison of IVUS and PET images with histology has not been performed. The aim of this study was to align IVUS and PET images using anatomic landmarks in Watanabe heritable hyperlipidaemic (WHHL) rabbits, enabling comparison of their depiction of aortic atherosclerosis. Cellular {sup 18}F-FDG localization was evaluated by {sup 3}H-FDG microautoradiography (micro-ARG). A total of 19 WHHL rabbits (7 months of age) were divided into three groups: baseline (n = 6), 3 months (n = 4), and 6 months (n = 9). PET, IVUS and histological images of the same aortic segments were analysed. Infiltration by foamy macrophages was scored from 0 to IV using haematoxylin and eosin (H and E) and antimacrophage immunohistochemical staining, and compared with {sup 3}H-FDG micro-ARG findings in two additional WHHL rabbits. IVUS images did not identify foamy macrophage deposition but revealed the area of intimal lesions (r = 0.87). {sup 18}F-FDG PET revealed foamy macrophage distribution in the plaques. The intensity of {sup 18}F-FDG uptake was correlated positively with the degree of foamy macrophage infiltration. Micro-ARG showed identical {sup 3}H-FDG accumulation in the foamy macrophages surrounding the lipid core of the plaques. F-FDG PET localized and quantified the degree of infiltration of foamy macrophages in atherosclerotic lesions. IVUS defined the size of lesions. {sup 18}F-FDG PET is a promising imaging technique for evaluating atherosclerosis and for monitoring changes in the composition of atherosclerotic plaques affecting their stability. (orig.)

  14. Peripheral ARtery Atherosclerotic DIsease and SlEep disordered breathing (PARADISE) trial - protocol for an observational cohort study.

    Science.gov (United States)

    Szymański, Filip M; Gałązka, Zbigniew; Płatek, Anna E; Górko, Dariusz; Ostrowski, Tomasz; Adamkiewicz, Karolina; Łęgosz, Paweł; Ryś, Anna; Semczuk-Kaczmarek, Karolina; Celejewski, Krzysztof; Filipiak, Krzysztof J

    2017-01-01

    increased oxidative stress and vascular endothelial injury associated with OSA, patients afflicted with this condition will not only have more advanced atherosclerotic lesions, but also in their histopathological examination their atherosclerotic plaque will exhibit evidence of greater instability and adverse morphology. We also expect to show that in patients with OSA, achieving cor¬rect control of cardiovascular risk factors will be more difficult. The study may improve PAD control through assuring better multispecialty care in PAD patients.

  15. An immunomodulating fatty acid analogue targeting mitochondria exerts anti-atherosclerotic effect beyond plasma cholesterol-lowering activity in apoe(-/- mice.

    Directory of Open Access Journals (Sweden)

    Rita Vik

    Full Text Available Tetradecylthioacetic acid (TTA is a hypolipidemic antioxidant with immunomodulating properties involving activation of peroxisome proliferator-activated receptors (PPARs and proliferation of mitochondria. This study aimed to penetrate the effect of TTA on the development of atherosclerotic lesions in apolipoprotein (apo-E(-/- mice fed a high-fat diet containing 0.3% TTA for 12 weeks. These mice displayed a significantly less atherosclerotic development vs control. Plasma cholesterol was increased by TTA administration and triacylglycerol (TAG levels in plasma and liver were decreased by TTA supplementation, the latter, probably due to increased mitochondrial fatty acid oxidation and reduced lipogenesis. TTA administration also changed the fatty acid composition in the heart, and the amount of arachidonic acid (ARA and eicosapentaenoic acid (EPA was reduced and increased, respectively. The heart mRNA expression of inducible nitric oxidase (NOS-2 was decreased in TTA-treated mice, whereas the mRNA level of catalase was increased. Finally, reduced plasma levels of inflammatory mediators as IL-1α, IL-6, IL-17, TNF-α and IFN-γ were detected in TTA-treated mice. These data show that TTA reduces atherosclerosis in apoE(-/- mice and modulates risk factors related to atherosclerotic disorders. TTA probably acts at both systemic and vascular levels in a manner independent of changes in plasma cholesterol, and triggers TAG catabolism through improved mitochondrial function.

  16. Identification of Atherosclerotic Plaques in Carotid Artery by Fluorescence Spectroscopy

    Science.gov (United States)

    Rocha, Rick; Villaverde, Antonio Balbin; Silveira, Landulfo; Costa, Maricília Silva; Alves, Leandro Procópio; Pasqualucci, Carlos Augusto; Brugnera, Aldo

    2008-04-01

    The aim of this work was to identify the presence of atherosclerotic plaques in carotid artery using the Fluorescence Spectroscopy. The most important pathogeny in the cardiovascular disorders is the atherosclerosis, which may affect even younger individuals. With approximately 1.2 million heart attacks and 750,000 strokes afflicting an aging American population each year, cardiovascular disease remains the number one cause of death. Carotid artery samples were obtained from the Autopsy Service at the University of São Paulo (São Paulo, SP, Brazil) taken from cadavers. After a histopathological analysis the 60 carotid artery samples were divided into two groups: normal (26) and atherosclerotic plaques (34). Samples were irradiated with the wavelength of 488 nm from an Argon laser. A 600 μm core optical fiber, coupled to the Argon laser, was used for excitation of the sample, whereas another 600 optical fiber, coupled to the spectrograph entrance slit, was used for collecting the fluorescence from the sample. Measurements were taken at different points on each sample and then averaged. Fluorescence spectra showed a single broad line centered at 549 nm. The fluorescence intensity for each sample was calculated by subtracting the intensity at the peak (550 nm) and at the bottom (510 nm) and then data were statistically analyzed, looking for differences between both groups of samples. ANOVA statistical test showed a significant difference (p<0,05) between both types of tissues, with regard to the fluorescence peak intensities. Our results indicate that this technique could be used to detect the presence of the atherosclerotic in carotid tissue.

  17. Atherosclerotic plaque detection by confocal Brillouin and Raman microscopies

    Science.gov (United States)

    Meng, Zhaokai; Basagaoglu, Berkay; Yakovlev, Vladislav V.

    2015-02-01

    Atherosclerosis, the development of intraluminal plaque, is a fundamental pathology of cardiovascular system and remains the leading cause of morbidity and mortality worldwide. Biomechanical in nature, plaque rupture occurs when the mechanical properties of the plaque, related to the morphology and viscoelastic properties, are compromised, resulting in intraluminal thrombosis and reduction of coronary blood flow. In this report, we describe the first simultaneous application of confocal Brillouin and Raman microscopies to ex-vivo aortic wall samples. Such a non-invasive, high specific approach allows revealing a direct relationship between the biochemical and mechanical properties of atherosclerotic tissue.

  18. Periodontal disease and risk of atherosclerotic coronary heart disease.

    Science.gov (United States)

    Nakajima, Takako; Yamazaki, Kazuhisa

    2009-07-01

    Atherosclerosis is an important component of coronary heart disease (CHD), which is the leading cause of death worldwide, including in Japan. Because atherosclerotic processes are typified by chronic inflammatory responses, which are similar to those elicited by chronic infection, the role of infection in promoting or accelerating atherosclerosis has received considerable focus. Increasing evidence supports the notion that periodontitis is associated with increased risk of atherosclerosis through dysfunction of endothelial cells induced by either periodontopathic bacteria or their products, or inflammatory mediators derived from infected periodontal tissue. Here we review whether periodontitis represents a risk factor for CHD or atherosclerosis, particularly in a Japanese population.

  19. Protein corona and phospholipase activity drive selective accumulation of nanomicelles in atherosclerotic plaques.

    Science.gov (United States)

    Lechuga-Vieco, Ana V; Groult, Hugo; Pellico, Juan; Mateo, Jesús; Enríquez, Jose A; Ruiz-Cabello, Jesús; Herranz, Fernando

    2018-01-06

    ApoB-100 and Phosphatidylcholine-specific phospholipase C (PC-PLC) are important contributors to atherosclerosis development. ApoB-100 is the main structural protein of LDL, being directly associated with atherosclerosis plaque generation. PC-PLC is highly expressed in atherosclerosis lesions and contributes to their progression. We show how phosphatidylcholine-coated nanomicelles can be used for specific characterisation of atherosclerosis plaque. Results show that ApoB-100 in the protein corona of the nanomicelle targets the particles to atherosclerotic areas in apolipoprotein E -/- mice. Furthermore, PC-PLC selectively removes the polar heads from the phospholipid coating of the nanomicelles leading to their accumulation. To fully characterise the behaviour of the nanomicelles, we developed multimodal probes using a nanoemulsion step. Hybrid imaging revealed plaque accumulation of the nanomicelles and colocalisation with PC-PLC expression and ApoB-100 in the plaque. This study shows how protein corona composition and enzyme-driven nanomaterial accumulation can be used for detection of atherosclerosis. Copyright © 2018. Published by Elsevier Inc.

  20. Application of an Integrative Computational Framework in Trancriptomic Data of Atherosclerotic Mice Suggests Numerous Molecular Players

    Directory of Open Access Journals (Sweden)

    Olga Papadodima

    2012-01-01

    Full Text Available Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throughout its manifestation. The present study aims to exploit bioinformatic tools in order to analyze microarray data of atherosclerotic aortic lesions of ApoE knockout mice, a model widely used in atherosclerosis research. In particular, a dynamic analysis was performed among young and aged animals, resulting in a list of 852 significantly altered genes. Pathway analysis indicated alterations in critical cellular processes related to cell communication and signal transduction, immune response, lipid transport, and metabolism. Cluster analysis partitioned the significantly differentiated genes in three major clusters of similar expression profile. Promoter analysis applied to functional related groups of the same cluster revealed shared putative cis-elements potentially contributing to a common regulatory mechanism. Finally, by reverse engineering the functional relevance of differentially expressed genes with specific cellular pathways, putative genes acting as hubs, were identified, linking functionally disparate cellular processes in the context of traditional molecular description.

  1. Characterization of atherosclerotic disease in thoracic aorta: A 3D, multicontrast vessel wall imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Changwu [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China); Department of Radiology, The Second Clinical Medical College, Yangzhou University, Yangzhou (China); Qiao, Huiyu; He, Le [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China); Yuan, Chun [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China); Department of Radiology, University of Washington, Seattle, WA (United States); Chen, Huijun; Zhang, Qiang; Li, Rui [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China); Wang, Wei; Du, Fang [Department of Radiology, The Second Clinical Medical College, Yangzhou University, Yangzhou (China); Li, Cheng, E-mail: cjr.licheng@vip.163.com [Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing (China); Zhao, Xihai, E-mail: xihaizhao@tsinghua.edu.cn [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China)

    2016-11-15

    Purpose: To investigate the characteristics of plaque in the thoracic aorta using three dimensional multicontrast magnetic resonance imaging. Materials and methods: Elderly subjects (≥60 years) were recruited in this study. Thoracic aorta was imaged on a 3.0T MR scanner by acquiring multicontrast sequences. The plaque burden was evaluated by measuring lumen area, wall area, wall thickness, and normalized wall index. The presence or absence of plaque and intraplaque hemorrhage (IPH)/mural thrombus (MT) were identified. The characteristics of atherosclerosis among different thoracic aorta segments (AAO: ascending aorta; AOA: aortic arch, and DOA: descending aorta) were determined. Results: Of 66 recruited subjects (mean age 72.3 ± 6.2 years, 30 males), 55 (83.3%) had plaques in the thoracic aorta. The prevalence of plaque in AAO, AOA, and DAO was 5.4%, 72.7%, and 71.2%, respectively. In addition, 21.2% of subjects were found to have lesions with IPH/MT in the thoracic aorta. The prevalence of IPH/MT in segment of AAO, AOA and DAO was 0%, 13.6%, and 12.1%, respectively. The aortic wall showed the highest NWI in DAO (34.1% ± 4.8%), followed by AOA (31.2% ± 5%), and AAO (26.8% ± 3.3%) (p < 0.001). Conclusion: Three dimensional multicontrast MR imaging is capable of characterizing atherosclerotic plaques in the thoracic aorta. The findings of high prevalence of plaques and the presence of high risk plaques in the thoracic aorta suggest early screening for aortic vulnerable lesions in the elderly.

  2. Talar Dome Lesion

    Science.gov (United States)

    ... Please enable Javascript in your browser. Talar Dome Lesion What Is a Talar Dome Lesion? The ankle joint is composed of the bottom ... on the specific case. Complications of Talar Dome Lesions Depending on the amount of damage to the ...

  3. Contrast enhancement by lipid-based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study

    NARCIS (Netherlands)

    den Adel, Brigit; van der Graaf, Linda M.; Que, Ivo; Strijkers, Gustav J.; Löwik, Clemens W.; Poelmann, Robert E.; van der Weerd, Louise

    2013-01-01

    The use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of two differently sized gadolinium-based contrast agents to enhance atherosclerotic plaques in ApoE(-/-) mice was evaluated with MRI. We

  4. Experience With Intravascular Ultrasound Imaging Of Human Atherosclerotic Arteries

    Science.gov (United States)

    Mallery, John A.; Gessert, James M.; Maciel, Mario; Tobis, John M.; Griffith, James M.; Berns, Michael W.; Henry, Walter L.

    1989-08-01

    Normal human arteries have a well-defined structure on intravascular images. The intima appears very thin and is most likely represented by a bright reflection arising from the internal elastic lamina. The smooth muscle tunica media is echo-lucent on the ultrasound image and appears as a dark band separating the intima from the adventitia. The adventitia is a brightly reflective layer of variable thickness. The thickness of the intima, and therefore of the atherosclerotic plaque can be accurately measured from the ultrasound images and correlates well with histology. Calcification within the wall of arteries is seen as bright echo reflection with shadowing of the peripheral wall. Fibrotic regions are highly reflective but do not shadow. Necrotic liquid regions within advanced atherosclerotic plaques are seen on ultrasound images as large lucent zones surrounded by echogenic tissue. Imaging can be performed before and after interventional procedures, such as laser angioplasty, balloon angioplasty and atherectomy. Intravascular ultrasound appears to provide an imaging modality for identifying the histologic characteristics of diseased arteries and for quantifying plaque thickness. It might be possible to perform such quantification to evaluate the results of interventional procedures.

  5. CO2 vascular anastomosis of atherosclerotic and calcified arteries

    Science.gov (United States)

    White, John V.; Leefmans, Eric; Stewart, Gwendolyn J.; Katz, Mira L.; Comerota, Anthony J.

    1990-06-01

    The technique for CO2 laser fusion vascular anastomosis in normal vessels has been well established. Normal arterial wall has a predictable thermal response to the incident laser energy, with rapid heating and cooling of collagen within the arterial wall. Since atherosclerosis involves subendothelial cellular proliferation, lipid and calcium deposition, it may modify the thermal responsiveness of the arterial wall. To this study, CO2 laser fusion anastomoses were attempted in rabbits with non-calcific atherosclerosis and humans with calcific atherosclerosis. All anastomoses were successfully completed without alteration in technique despite the presence of plaque at the site of laser fusion. Histology of rabbit vessels revealed the classic laser fusion cap within the adventitia and persistent atherosclerotic plaque at the flow surface. Duplex imaging of patients post-operatively demonstrated long term anastomotic patency in 2 of 3 fistulae. These results suggest that neither non-calcified or calcified atherosclerosis significantly alters the arterial wall thermal responsiveness to CO2 laser energy or inhibits creation of laser fusion anastomoses. Therefore, this technique may be applicable to the treatment of patients with atherosclerotic occlusive disease.

  6. Tensile and compressive properties of fresh human carotid atherosclerotic plaques.

    LENUS (Irish Health Repository)

    Maher, Eoghan

    2009-12-11

    Accurate characterisation of the mechanical properties of human atherosclerotic plaque is important for our understanding of the role of vascular mechanics in the development and treatment of atherosclerosis. The majority of previous studies investigating the mechanical properties of human plaque are based on tests of plaque tissue removed following autopsy. This study aims to characterise the mechanical behaviour of fresh human carotid plaques removed during endarterectomy and tested within 2h. A total of 50 radial compressive and 17 circumferential tensile uniaxial tests were performed on samples taken from 14 carotid plaques. The clinical classification of each plaque, as determined by duplex ultrasound is also reported. Plaques were classified as calcified, mixed or echolucent. Experimental data indicated that plaques were highly inhomogeneous; with variations seen in the mechanical properties of plaque obtained from individual donors and between donors. The mean behaviour of samples for each classification indicated that calcified plaques had the stiffest response, while echolucent plaques were the least stiff. Results also indicated that there may be a difference in behaviour of samples taken from different anatomical locations (common, internal and external carotid), however the large variability indicates that more testing is needed to reach significant conclusions. This work represents a step towards a better understanding of the in vivo mechanical behaviour of human atherosclerotic plaque.

  7. Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques.

    Science.gov (United States)

    Honoré, E K; Williams, J K; Anthony, M S; Clarkson, T B

    1997-01-01

    To examine the effects of soy phytoestrogens on coronary vascular reactivity in atherosclerotic male and female rhesus monkeys. A prospective, randomized, blinded, controlled study. Comparative Medicine Clinical Research Center of an academic medical center. Twenty-two young adult rhesus monkeys with pre-existing diet-induced atherosclerosis. Monkeys were fed soy-based diets for 6 months identical in composition, except that the isoflavones were extracted from one flow-isoflavone) and intact in the other (high-isoflavone). Quantitative coronary angiography was performed at the end of the study period. Females in the low-isoflavone group under went a second angiography after an acute IV dose of genistein. Percent change in diameter of the proximal left circumflex coronary artery in response to intracoronary acetylcholine and nitroglycerin, compared with control diameter. Arteries from males constricted in response to acetylcholine. Arteries from females in the low-isoflavone group constricted (-6.2% +/- 2.8%, mean +/- SEM), whereas arteries from females in the high-isoflavone group dilated (6.4% +/- 1.2%, mean +/- SEM). Intravenous administration of genistein caused dilation in the previously constricting low-isoflavone females (3.3% +/- 2.8%). Like mammalian estrogens, dietary soy isoflavones enhance the dilator response to acetylcholine of atherosclerotic arteries in female monkeys.

  8. Associations of Osteocalcin, Osteoprotegerin, and Calcitonin with Inflammation Biomarkers in Atherosclerotic Plaques of Coronary Arteries.

    Science.gov (United States)

    Polonskaya, Ya V; Kashtanova, E V; Murashov, I S; Volkov, A M; Kurguzov, A V; Chernyavsky, A M; Ragino, Yu I

    2017-04-01

    We studied associations of osteocalcin, osteoprotegerin, and calcitonin with markers of inflammation in atherosclerotic plaques in coronary arteries and assessed the influence of these biomolecules on calcification of atherosclerotic plaques. The initial stage of calcification of atherosclerotic plaques is characterized by activation of inflammatory processes, which is seen from increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-α, and IL-1β). Progressive calcification of atherosclerotic plaques is accompanied by insignificant accumulation of calcitonin and osteoprotegerin. The exception is osteocalcin, its concentration significantly increased during calcification. The results suggest that severe vascular calcification can be regarded as non-specific marker of atherosclerosis. Instability of atherosclerotic plaques is associated with higher level of calcification.

  9. Earlobe crease in women: evaluation of reproductive factors, alcohol use, and Quetelet index and relation to atherosclerotic disease.

    Science.gov (United States)

    Petrakis, N L

    1995-10-01

    The diagonal earlobe crease (ELC) has been found to be associated with atherosclerotic heart disease. Although atherosclerotic cardiovascular disease is less prevalent among women than among men, no studies have been reported for women on the possible relationship of reproductive factors, contraceptive and menopausal estrogen use, and alcohol use on the expression of the ELC. The presence of ELC was determined in 625 white women who were seen as part of a breast research project. Information was obtained on age, height, weight, age at menarche, parity, age at first full-term pregnancy, use of oral contraceptives or menopausal estrogens, alcohol consumption, and smoking. Statistical methods used included estimation of the age-adjusted odds ratios and their 95% confidence intervals, and multiple logistic regression. No association was found between the ELC and reproductive factors and smoking. Only age, Quetelet index, and alcohol use were associated with the ELC. The ELC was negatively associated with alcohol use, and was more marked in women under 59 years of age. The positive association of ELC with the Quetelet index progressively became more marked with advancing age, especially after 60 years of age. The negative association found between the ELC and alcohol use is of interest because of the reported protective effect of moderate alcohol consumption on risk of coronary heart disease. No significant association was found between the ELC and reproductive risk factors. Based on events occurring during the embryonic development of the earlobes, a new hypothesis is proposed for the formation and peculiar diagonal localization of the ELC in adult earlobes in association with atherosclerotic vascular disease.

  10. F-18 fluoride positron emission tomography-computed tomography for detecting atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Won Jun [Dept. of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-12-15

    A large number of major cardiovascular events occur in patients due to minimal or some lumen narrowing of the coronary artery. Recent biological studies have shown that the biological composition or vulnerability of the plaque is more critical for plaque rupture compared to the degree of stenosis. To overcome the limitations of anatomical images, molecular imaging techniques have been suggested as promising imaging tools in various fields. F-18 fluorodeoxyglucose (FDG), which is widely used in the field of oncology, is an example of molecular probes used in atherosclerotic plaque evaluation. FDG is a marker of plaque macrophage glucose utilization and inflammation, which is a prominent characteristic of vulnerable plaque. Recently, F-18 fluoride has been used to visualize vulnerable plaque in clinical studies. F-18 fluoride accumulates in regions of active microcalcification, which is normally observed during the early stages of plaque formation. More studies are warranted on the accumulation of F-18 fluoride and plaque formation/vulnerability; however, due to high specific accumulation, low background activity, and easy accessibility, F-18 fluoride is emerging as a promising non-invasive imaging probe to detect vulnerable plaque.

  11. An unexpected intriguing effect of Toll-like receptor regulator RP105 (CD180) on atherosclerosis formation with alterations on B-cell activation.

    Science.gov (United States)

    Karper, J C; de Jager, S C A; Ewing, M M; de Vries, M R; Bot, I; van Santbrink, P J; Redeker, A; Mallat, Z; Binder, C J; Arens, R; Jukema, J W; Kuiper, J; Quax, P H A

    2013-12-01

    In atherosclerosis, Toll-like receptors (TLRs) are traditionally linked to effects on tissue macrophages or foam cells. RP105, a structural TLR4 homolog, is an important regulator of TLR signaling. The effects of RP105 on TLR signaling vary for different leukocyte subsets known to be involved in atherosclerosis, making it unique in its role of either suppressing (in myeloid cells) or enhancing (in B cells) TLR-regulated inflammation in different cell types. We aimed to identify a role of TLR accessory molecule RP105 on circulating cells in atherosclerotic plaque formation. Irradiated low density lipoprotein receptor deficient mice received RP105(-/-) or wild-type bone marrow. RP105(-/-) chimeras displayed a 57% reduced plaque burden. Interestingly, total and activated B-cell numbers were significantly reduced in RP105(-/-) chimeras. Activation of B1 B cells was unaltered, suggesting that RP105 deficiency only affected inflammatory B2 B cells. IgM levels were unaltered, but anti-oxidized low-density lipoprotein and anti-malondialdehyde-modified low-density lipoprotein IgG2c antibody levels were significantly lower in RP105(-/-) chimeras, confirming effects on B2 B cells rather than B1 B cells. Moreover, B-cell activating factor expression was reduced in spleens of RP105(-/-) chimeras. RP105 deficiency on circulating cells results in an intriguing unexpected TLR-associated mechanisms that decrease atherosclerotic lesion formation with alterations on proinflammatory B2 B cells.

  12. Distribution of selected elements in atherosclerotic plaques of apoE/LDLR-double knockout mice subjected to dietary and pharmacological treatments

    Energy Technology Data Exchange (ETDEWEB)

    Gajda, Mariusz, E-mail: mmgajda@cyf-kr.edu.pl [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Kowalska, Joanna [Institute of Nuclear Physics, Radzikowskiego 152, 31-342 Krakow (Poland); Banas, Agnieszka; Banas, Krzysztof [Singapore Synchrotron Light Source, National University of Singapore, 5 Research Link, 117603 Singapore (Singapore); Kwiatek, Wojciech M. [Institute of Nuclear Physics, Radzikowskiego 152, 31-342 Krakow (Poland); Kostogrys, Renata B. [Department of Human Nutrition, Agricultural University of Krakow, Balicka 122, 30-149, Krakow (Poland); Mateuszuk, Lukasz; ChLopicki, Stefan [Department of Experimental Pharmacology, Jagiellonian University Medical College, Kopernika 7, 31-531 Krakow (Poland); Litwin, Jan A. [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Appel, Karen [Hasylab, DESY, Notkestrasse 85, D-22607, Hamburg (Germany)

    2011-10-15

    Gene-targeted, apolipoprotein E and LDL receptor-double knockout (apoE/LDLR{sup -/-}) mice represent a new animal model that displays severe hyperlipidemia and atherosclerosis. The aim of the present study was to show changes in histomorphology and in distribution of selected elements in atherosclerotic plaques of apoE/LDLR{sup -/-} mice fed egg-rich proatherosclerotic diet (5% egg-yolk lyophilisate) supplemented or not with perindopril (inhibitor of angiotensin converting enzyme; 2 mg/kg b.w.). Synchrotron radiation micro-X-ray fluorescence spectrometry was combined with histological stainings to determine distribution and concentration of trace and essential elements in atherosclerotic lesions. More advanced atherosclerotic lesions expressed by total area occupied by lipids (oil red-O staining) and by macrophages (CD68 immunohistochemistry) were observed in animals fed egg-rich diet. The perindopril treatment attenuated these effects. No significant differences were observed in the number of intimal smooth muscle cells (smooth muscle actin immunohistochemistry). In animals fed egg-rich diet significantly higher concentrations of Ca and significantly lower contents of S, Cl, , Fe, Cu, Zn and Se in atheromas were seen in comparison to chow diet-fed animals. After pharmacological treatment, concentrations of S, Cl, Fe, Cu, Zn and Se showed the tendency to achieve levels like in animals fed normal diet. K level differed only in group treated with perindopril. Concentration of P did not significantly vary in all experimental groups. Perindopril showed its potency to reduce atherosclerosis, as estimated by the size of the atheroma and content of pro- and antiatherogenic elements.

  13. Genistein Supplementation Inhibits Atherosclerosis with Stabilization of the Lesions in Hypercholesterolemic Rabbits

    OpenAIRE

    Lee, Choong-Sik; Kwon, Su-Jin; Na, Sun-Young; Lim, Seung-Pyung; Lee, Jung-Hee

    2004-01-01

    The effect of genistein on aortic atherosclerosis was studied by immunohistochemistry with RAM-11 and HHF-35 antibodies and western blotting for matrix metalloproteinase-3 (MMP-3) in New Zealand White rabbits. After provocation of atherosclerosis with hyperlipidemic diet, the rabbits were divided as hyperlipidemic diet group (HD), normal diet group (ND) and hyperlipidemic plus genistein diet group (HD+genistein) for 4 and half months. The average cross sectional area of atherosclerotic lesion...

  14. Long-term stable expression of human apolipoprotein A-I mediated by helper-dependent adenovirus gene transfer inhibits atherosclerosis progression and remodels atherosclerotic plaques in a mouse model of familial hypercholesterolemia.

    Science.gov (United States)

    Belalcazar, L Maria; Merched, Aksam; Carr, Boyd; Oka, Kazuhiro; Chen, Kuang-Hua; Pastore, Lucio; Beaudet, Arthur; Chan, Lawrence

    2003-06-03

    Epidemiologic studies and transgenic mouse experiments indicate that high plasma HDL and apolipoprotein (apo) A-I protect against atherosclerosis. We used helper-dependent adenovirus (HD-Ad) gene transfer to examine the effect of long-term hepatic apoA-I expression on atherosclerotic lesion progression and remodeling in a mouse model of familial hypercholesterolemia. We treated LDL receptor-deficient (LDLR-/-) mice maintained on a high-cholesterol diet for 6 weeks with either a HD-Ad containing human apoA-I gene (HD-Ad-AI) or saline (control). HD-Ad-AI treatment did not affect plasma liver enzymes but induced the appearance of plasma human apoA-I at or above human levels for the duration of the study. Substantial amounts of human apoA-I existed in lipid-free plasma. Compared with controls, HDLs from treated mice were larger and had a greater inhibitory effect on tumor necrosis factor-alpha-induced vascular cellular adhesion molecule-1 expression in cultured endothelial cells. Twenty-four weeks after injection, aortic atherosclerotic lesion area in saline-treated mice progressed approximately 700%; the rate of progression was reduced by >50% by HD-Ad-AI treatment. The lesions in HD-Ad-AI-treated mice contained human apoA-I that colocalized mainly with macrophages; they also contained less lipid, fewer macrophages, and less vascular cellular adhesion molecule-1 immunostaining but more smooth muscle cells (alpha-actin staining) and collagen. HD-Ad-AI treatment of LDLR-/- mice leads to long-term overexpression of apoA-I, retards atherosclerosis progression, and remodels the lesions to a more stable-appearing phenotype. HD-Ad-mediated transfer of apoA-I may be a useful clinical approach for protecting against atherosclerosis progression and stabilizing atherosclerotic lesions associated with dyslipidemia in human patients.

  15. CD154: the atherosclerotic risk factor in rheumatoid arthritis?

    Science.gov (United States)

    2013-01-01

    Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features. Indeed, evidence pertaining to this matter indicates that inflammation and its multiple components are the driving force behind the pathogenesis of these disorders. Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications. Indeed, CD154 signaling elicits critical inflammatory responses that are common to the pathogenesis of both diseases. Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients. PMID:23433179

  16. The Evolving Paradigm in the Management of Intracranial Atherosclerotic Disease

    Directory of Open Access Journals (Sweden)

    Ali K. Ozturk

    2012-01-01

    Full Text Available Intracranial atherosclerotic disease (ICAD is a major cause of ischemic stroke worldwide and represents a significant health problem. The pathogenesis and natural history of ICAD are poorly understood, and rigorous treatment paradigms do not exist as they do for extracranial atherosclerosis. Currently, the best treatment for ICAD remains aspirin therapy, but many patients who are placed on aspirin continue to experience recurrent strokes. As microsurgical and endovascular techniques continue to evolve, the role of extracranial to intracranial bypass operations and stenting are increasingly being reconsidered. We performed a PubMed review of the English literature with a particular focus on treatment options for ICAD and present evidence-based data for the role of surgery and stenting in ICAD against medical therapy alone.

  17. Gene expression and 18FDG uptake in atherosclerotic carotid plaques

    DEFF Research Database (Denmark)

    Pedersen, Sune Folke; Græbe, Martin; Hag, Anne Mette Fisker

    2010-01-01

    by carotid endarterectomy. The gene expression of markers of vulnerability - CD68, IL-18, matrix metalloproteinase 9, cathepsin K, GLUT-1, and hexokinase type II (HK2) - were measured in plaques by quantitative PCR. RESULTS: In a multivariate linear regression model, GLUT-1, CD68, cathepsin K, and HK2 gene......) and an additional ipsilateral internal carotid artery stenosis of greater than 60% were recruited. FDG uptake in the carotids was determined by PET/computed tomography and expressed as mean and maximal standardized uptake values (SUVmean and SUVmax). The atherosclerotic plaques were subsequently recovered...... destabilization. Accordingly, FDG-PET could prove to be an important predictor of cerebrovascular events in patients with carotid plaques....

  18. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G

    2016-01-01

    Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need...... that triglyceride-rich lipoproteins are causally associated with ASCVD and all-cause mortality. Finally, genetic evidence also demonstrates that high concentrations of triglyceride-rich lipoproteins are causally associated with low-grade inflammation. This suggests that an important part of inflammation...... in atherosclerosis and ASCVD is because of triglyceride-rich lipoprotein degradation and uptake into macrophage foam cells in the arterial intima. Taken together, new insights now strongly suggest that elevated triglyceride-rich lipoproteins represent causal risk factors for low-grade inflammation, ASCVD, and all...

  19. Low-density lipoproteins cause atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Ference, Brian A.; Ginsberg, Henry N.; Graham, Ian

    2017-01-01

    Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from...... genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL...... receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies...

  20. Ticagrelor promotes atherosclerotic plaque stability in a mouse model of advanced atherosclerosis.

    Science.gov (United States)

    Preusch, Michael R; Rusnak, Jonas; Staudacher, Kathrin; Mogler, Carolin; Uhlmann, Lorenz; Sievers, Philipp; Bea, Florian; Katus, Hugo A; Blessing, Erwin; Staudacher, Ingo

    2016-01-01

    There is increasing evidence supporting the role of platelets in atherosclerotic vascular disease. The G-protein-coupled receptor P2Y12 is a central mediator of platelet activation and aggregation but has also been linked to platelet-independent vascular disease. Ticagrelor is an oral P2Y12 antagonist that is used as a standard treatment in patients after acute myocardial infarction. However, the effects of ticagrelor on advanced atherosclerosis have not been investigated. Twenty-week-old apolipoprotein-E-deficient mice received standard chow or standard chow supplemented with 0.15% ticagrelor (approximately 270 mg/kg/day) for 25 weeks. The lesion area was evaluated in the aortic sinus by Movat's pentachrome staining and lesion composition, thickness of the fibrous cap, and size of the necrotic core evaluated by morphometry. RAW 264.7 macrophages were serum starved and treated with ticagrelor in vitro for the detection and quantification of apoptosis. In addition, oxLDL uptake in RAW 264.7 macrophages was evaluated. A trend toward the reduction of total lesion size was detected. However, data did not reach the levels of significance (control, n=11, 565,881 μm(2) [interquartile range {IQR} 454,778-603,925 μm(2)] versus ticagrelor, n=13, 462,595 μm(2) [IQR 379,740-546,037 μm(2)]; P=0.1). A significant reduction in the relative area of the necrotic core (control, n=11, 0.46 [IQR 0.4-0.51] versus ticagrelor, n=13, 0.34 [IQR 0.31-0.39]; P=0.008), and a significant increase in fibrous caps thickness (control, n=11, 3.7 μm [IQR 3.4-4.2 μm] versus ticagrelor, n=13, 4.7 [IQR 4.3-5.5 μm], P=0.04) were seen in ticagrelor-treated mice. In vitro studies demonstrated a reduction in apoptotic RAW 264.7 macrophages (control 0.07±0.03 versus ticagrelor 0.03±0.03; P=0.0002) when incubated with ticagrelor. Uptake of oxLDL in RAW 264.7 was significantly reduced when treated with ticagrelor (control 9.2 [IQR 5.3-12.9] versus ticagrelor 6.4 [IQR 2.5-9.5], P=0.02). The present

  1. Tissue factor pathway inhibitor gene delivery using HVJ-AVE liposomes markedly reduces restenosis in atherosclerotic arteries.

    Science.gov (United States)

    Yin, Xinhua; Yutani, Chikao; Ikeda, Yoshihiko; Enjyoji, Keiichi; Ishibashi-Ueda, Hatsue; Yasuda, Satoshi; Tsukamoto, Yoshitane; Nonogi, Hiroshi; Kaneda, Yasufumi; Kato, Hisao

    2002-12-01

    Tissue factor pathway inhibitor (TFPI), as a primary inhibitor of TF-induced coagulation, reduces neointimal formation and luminal stenosis by inhibiting coagulation and thrombosis after vessel wall injury. Here, we investigated the effect of TFPI gene delivery with a HVJ-AVE liposome vector on restenosis in atherosclerotic arteries after angioplasty in rabbits. We also evaluated the safety of the novel gene therapeutic strategy to prevent restenosis. Local iliac artery atherosclerosis was induced by a combination of balloon denudation and high-cholesterol diet in Japanese white rabbits, which were then subjected to angioplasty. Infusion of an HVJ-AVE liposome containing the TFPI gene or an "empty" pcDNA 3.1 expression vector, or HVJ-liposome vector only, or saline was performed at the site of angioplasty using a Dispatch((R)) catheter. Quantitative angiography and histopathology were performed before and after gene delivery and at 4 weeks follow-up. The safety of the gene therapy was evaluated over a 6-month observation period. TFPI mRNA and protein were detected in local TFPI gene transferred vessels after gene transfer. The mean minimal luminal diameter of the TFPI group was markedly greater than that of the control groups (PHVJ-AVE liposome-mediated TFPI gene transfer. HVJ-AVE liposome-mediated TFPI gene transfer significantly reduced neointimal hyperplasia, inhibited thrombosis, and attenuated vascular remodeling and lumimal stenosis after angioplasty in atherosclerotic arteries without any significant adverse effects.

  2. The role of Visfatin in atherosclerotic peripheral arterial obstructive disease.

    Science.gov (United States)

    Pitoulias, Matthaios G; Skoura, Lemonia; Pitoulias, Apostolos G; Chatzidimitriou, Dimitris; Margariti, Apostolia; Arsenakis, Minas; Pitoulias, Georgios A

    2017-03-01

    Visfatin is an adipokine molecule acting as an essential coenzyme in multiple cellular redox reactions. The increased serum levels of Visfatin have been correlated with metabolic syndrome and endothelial homeostasis. In this study we investigate the possible relationship of Visfatin serum levels with the severity and location of atherosclerotic peripheral arterial occlusive disease (PAOD). Study protocol included 45 consecutive PAOD and 20 Control patients with age >55years old. Definition of PAOD was based in Rutherord's classification (RC). End-stage PAOD patients (RC-V & -VI) were excluded from study. Data were collected prospectively and included age, gender, atherosclerotic risk factors and the body mass index (BMI). In PAOD patients recorded the PAOD's clinical stage and the presence of carotid stenosis >50%. PAOD patients divided in two subgroups, those with mild (RC-I & -II) and moderate disease (RC-III & -IV). In all serum samples Visfatin was measured, blindly, twice by anosoenzymatic technique. Statistical analysis was performed by non-parametric Mann-Whitney U test, Pearson's chi-square, One Way Anova and Kruskall-Wallis tests, as appropriate. The mean Visfatin value in PAOD and Control groups were 38.5±16.0 and 13.9±3.8ng/ml respectively (p0.05). Univariate analysis showed that severity of PAOD (mild vs severe), presence of carotid stenosis >50% and multilevel disease significantly affected outcomes (p=0.018, p=0.010 and p=0.006 respectively). In multivariate regression analysis severity of PAOD was the solely factor with strong correlation with high visfatin values (p=0.001). High Visfatin levels seem to be strongly correlated with the presence and severity of PAOD. Further and in depth investigation is needed to define the possible role of Visfatin in atherosclerosis and it's value as a potential prognostic biomarker of PAOD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Uptake of inflammatory cell marker [{sup 11}C]PK11195 into mouse atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Laitinen, Iina; Marjamaeki, Paeivi; Naagren, Kjell; Roivainen, Anne; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Laine, V.J.O. [Turku University Hospital, Department of Pathology, Turku (Finland); Wilson, Ian [GE Healthcare Biosciences, Medical Diagnostics, London (United Kingdom); Leppaenen, Pia; Ylae-Herttuala, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland)

    2009-01-15

    The ligand [{sup 11}C]PK11195 binds with high affinity and selectivity to peripheral benzodiazepine receptor, expressed in high amounts in macrophages. In humans, [{sup 11}C]PK11195 has been used successfully for the in vivo imaging of inflammatory processes of brain tissue. The purpose of this study was to explore the feasibility of [{sup 11}C]PK11195 in imaging inflammation in the atherosclerotic plaques. The presence of PK11195 binding sites in the atherosclerotic plaques was verified by examining the in vitro binding of [{sup 3}H]PK11195 onto mouse aortic sections. Uptake of intravenously administered [{sup 11}C]PK11195 was studied ex vivo in excised tissue samples and aortic sections of a LDLR/ApoB48 atherosclerotic mice. Accumulation of the tracer was compared between the atherosclerotic plaques and non-atherosclerotic arterial sites by autoradiography and histological analyses. The [{sup 3}H]PK11195 was found to bind to both the atherosclerotic plaques and the healthy wall. The autoradiography analysis revealed that the uptake of [{sup 11}C]PK11195 to inflamed regions in plaques was more prominent (p = 0.011) than to non-inflamed plaque regions, but overall it was not higher than the uptake to the healthy vessel wall. Also, the accumulation of {sup 11}C radioactivity into the aorta of the atherosclerotic mice was not increased compared to the healthy control mice. Our results indicate that the uptake of [{sup 11}C]PK11195 is higher in inflamed atherosclerotic plaques containing a large number of inflammatory cells than in the non-inflamed plaques. However, the tracer uptake to other structures of the artery wall was also prominent and may limit the use of [{sup 11}C]PK11195 in clinical imaging of atherosclerotic plaques. (orig.)

  4. Detection of Atherosclerotic Inflammation by (68)Ga-DOTATATE PET Compared to [(18)F]FDG PET Imaging.

    Science.gov (United States)

    Tarkin, Jason M; Joshi, Francis R; Evans, Nicholas R; Chowdhury, Mohammed M; Figg, Nichola L; Shah, Aarti V; Starks, Lakshi T; Martin-Garrido, Abel; Manavaki, Roido; Yu, Emma; Kuc, Rhoda E; Grassi, Luigi; Kreuzhuber, Roman; Kostadima, Myrto A; Frontini, Mattia; Kirkpatrick, Peter J; Coughlin, Patrick A; Gopalan, Deepa; Fryer, Tim D; Buscombe, John R; Groves, Ashley M; Ouwehand, Willem H; Bennett, Martin R; Warburton, Elizabeth A; Davenport, Anthony P; Rudd, James H F

    2017-04-11

    Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET), [(18)F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. This study tested the efficacy of gallium-68-labeled DOTATATE ((68)Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation. We confirmed (68)Ga-DOTATATE binding in macrophages and excised carotid plaques. (68)Ga-DOTATATE PET imaging was compared to [(18)F]FDG PET imaging in 42 patients with atherosclerosis. Target SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific (68)Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo (68)Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). (68)Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). (68)Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p 68)Ga-DOTATATE PET scans were readable in all patients. We validated (68)Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that (68)Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [(18)F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188). Copyright

  5. Expression of the vitamin K-dependent proteins GAS6 and protein S and the TAM receptor tyrosine kinases in human atherosclerotic carotid plaques.

    Science.gov (United States)

    Hurtado, B; Muñoz, X; Recarte-Pelz, P; García, N; Luque, A; Krupinski, J; Sala, N; García de Frutos, P

    2011-05-01

    The GAS6/ProS-TAM system is composed of two vitamin K-dependent ligands (GAS6 and protein S) and their three protein tyrosine kinase receptors TYRO3, AXL and MERTK, known as the TAM receptors. The system plays a prominent role in conditions of injury, inflammation and repair. In murine models of atherosclerotic plaque formation, mutations in its components affect atherosclerosis severity. Here we used Taqman low-density arrays and immunoblotting to study mRNA and protein expression of GAS6, ProS and the TAM receptors in human carotid arteries with different degrees of atherosclerosis. The results show a clear down-regulation of the expression of AXL in atheroma plaques with respect to normal carotids that is matched by decreased abundance of AXL in protein extracts detected by immunoblotting. A similar decrease was observed in PROS1 mRNA expression in atherosclerotic carotids compared to the normal ones, but in this case protein S (ProS) was clearly increased in protein extracts of carotid arteries with increasing grade of atherosclerosis, suggesting that ProS is carried into the plaque. MERTK was also increased in atherosclerotic carotid arteries with respect to the normal ones, suggesting that the ProS-MERTK axis is functional in advanced human atherosclerotic plaques. MERTK was expressed in macrophages, frequently in association with ProS, while ProS was abundant also in the necrotic core. Our data suggest that the ProS-MERTK ligand-receptor pair was active in advanced stages of atherosclerosis, while AXL signalling is probably down-regulated.

  6. SPECT/CT Imaging of High-Risk Atherosclerotic Plaques using Integrin-Binding RGD Dimer Peptides.

    Science.gov (United States)

    Yoo, Jung Sun; Lee, Jonghwan; Jung, Jae Ho; Moon, Byung Seok; Kim, Soonhag; Lee, Byung Chul; Kim, Sang Eun

    2015-06-30

    Vulnerable atherosclerotic plaques with unique biological signatures are responsible for most major cardiovascular events including acute myocardial infarction and stroke. However, current clinical diagnostic approaches for atherosclerosis focus on anatomical measurements such as the degree of luminal stenosis and wall thickness. An abundance of neovessels with elevated expression of integrin αvβ3 is closely associated with an increased risk of plaque rupture. Herein we evaluated the potential of an αvβ3 integrin-targeting radiotracer, (99m)Tc-IDA-D-[c(RGDfK)]2, for SPECT/CT imaging of high-risk plaque in murine atherosclerosis models. In vivo uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 was significantly higher in atherosclerotic aortas than in relatively normal aortas. Comparison with the negative-control peptide, (99m)Tc-IDA-D-[c(RADfK)]2, proved specific binding of (99m)Tc-IDA-D-[c(RGDfK)]2 for plaque lesions in in vivo SPECT/CT and ex vivo autoradiographic imaging. Histopathological characterization revealed that a prominent SPECT signal of (99m)Tc-IDA-D-[c(RGDfK)]2 corresponded to the presence of high-risk plaques with a large necrotic core, a thin fibrous cap, and vibrant neoangiogenic events. Notably, the RGD dimer based (99m)Tc-IDA-D-[c(RGDfK)]2 showed better imaging performance in comparison with the common monomeric RGD peptide probe (123)I-c(RGDyV) and fluorescence tissue assay corroborated this. Our preclinical data demonstrated that (99m)Tc-IDA-D-[c(RGDfK)]2 SPECT/CT is a sensitive tool to noninvasively gauge atherosclerosis beyond vascular anatomy by assessing culprit plaque neovascularization.

  7. Comparison between MDCT and Grayscale IVUS in a Quantitative Analysis of Coronary Lumen in Segments with or without Atherosclerotic Plaques

    Energy Technology Data Exchange (ETDEWEB)

    Falcão, João L. A. A.; Falcão, Breno A. A. [Heart Institute (InCor), University of São Paulo Medical School (USP), São Paulo, SP (Brazil); Gurudevan, Swaminatha V. [Cedars-Sinai Heart Institute, Los Angeles, California, USA (United States); Campos, Carlos M.; Silva, Expedito R.; Kalil-Filho, Roberto; Rochitte, Carlos E.; Shiozaki, Afonso A.; Coelho-Filho, Otavio R.; Lemos, Pedro A. [Heart Institute (InCor), University of São Paulo Medical School (USP), São Paulo, SP (Brazil)

    2015-04-15

    The diagnostic accuracy of 64-slice MDCT in comparison with IVUS has been poorly described and is mainly restricted to reports analyzing segments with documented atherosclerotic plaques. We compared 64-slice multidetector computed tomography (MDCT) with gray scale intravascular ultrasound (IVUS) for the evaluation of coronary lumen dimensions in the context of a comprehensive analysis, including segments with absent or mild disease. The 64-slice MDCT was performed within 72 h before the IVUS imaging, which was obtained for at least one coronary, regardless of the presence of luminal stenosis at angiography. A total of 21 patients were included, with 70 imaged vessels (total length 114.6 ± 38.3 mm per patient). A coronary plaque was diagnosed in segments with plaque burden > 40%. At patient, vessel, and segment levels, average lumen area, minimal lumen area, and minimal lumen diameter were highly correlated between IVUS and 64-slice MDCT (p < 0.01). However, 64-slice MDCT tended to underestimate the lumen size with a relatively wide dispersion of the differences. The comparison between 64-slice MDCT and IVUS lumen measurements was not substantially affected by the presence or absence of an underlying plaque. In addition, 64-slice MDCT showed good global accuracy for the detection of IVUS parameters associated with flow-limiting lesions. In a comprehensive, multi-territory, and whole-artery analysis, the assessment of coronary lumen by 64-slice MDCT compared with coronary IVUS showed a good overall diagnostic ability, regardless of the presence or absence of underlying atherosclerotic plaques.

  8. Bilateral symmetry of local inflammatory activation in human carotid atherosclerotic plaques.

    Science.gov (United States)

    Benetos, Georgios; Toutouzas, Konstantinos; Drakopoulou, Maria; Tolis, Elias; Masoura, Constantina; Nikolaou, Charalampia; Tsekoura, Dorothea; Tsiamis, Eleftherios; Grassos, Harris; Siores, Elias; Stefanadis, Christodoulos; Tousoulis, Dimitris

    2015-01-01

    Only a few studies have investigated the structural and functional characteristics of carotid arteries bilaterally. Furthermore, there is controversy as to whether inflammation in paired vascular beds is a local or systemic phenomenon. We aimed to examine, in patients with coronary artery disease, whether intra-subject left and right carotid arteries have similar inflammatory status, as determined non-invasively by microwave radiometry (MWR). Consecutive patients (n=200) with significant coronary artery disease were evaluated via an ultrasound echo-colour Doppler (US-ECD) study of both carotid arteries and temperature measurements with MWR. During thermography, thermal heterogeneity (ΔT) was defined as the maximum temperature along the carotid artery minus the minimum temperature. Mean T was similar between the left and right carotid arteries (0.78 ± 0.48 vs. 0.84 ± 0.52°C, p=0.12). Mean right intima-media thickness (IMT) was greater compared to mean left IMT (2.16 ± 1.20 vs. 1.93 ± 0.94 mm, p<0.01). In all carotids, there was a correlation between left and right carotid plaque ΔT (R=0.38, p<0.001) and between left and right IMT (R=0.48, p<0.001). Independent predictors for the presence of bilateral carotid plaques were found to be the extent of coronary artery disease, high ΔT, and therapy with angiotensin II receptor blockers; predictors for the presence of high ΔT bilaterally were bilateral carotid plaques, male sex, diabetes mellitus, and hypertension. There is bilateral inflammatory activation in the carotid atherosclerotic lesions of patients with coronary artery disease. At this stage of carotid disease, arterial hypertension and diabetes mellitus are more strongly correlated with bilateral functional abnormalities in carotid plaques than with structural changes.

  9. Relationship between an increased serum kynurenine/tryptophan ratio and atherosclerotic parameters in hemodialysis patients.

    Science.gov (United States)

    Kato, Akihiko; Suzuki, Yuzo; Suda, Takafumi; Suzuki, Masako; Fujie, Michio; Takita, Takako; Furuhashi, Mitsuyoshi; Maruyama, Yukitaka; Chida, Kingo; Hishida, Akira

    2010-10-01

    Essential amino acid tryptophan (Trp) is mainly catabolized by indoleamine 2,3-dioxygenase, which leads to the formation of kynurenine (Kyn). In this study, we reexamined whether an increased indoleamine 2,3-dioxygenase activity, as estimated by the Kyn/Trp ratio (μM/mM), is associated with atherosclerotic parameters in hemodialysis (HD) patients. Serum Trp and Kyn were measured in 243 HD patients by liquid chromatography/electrospray ionization tandem mass spectrometry. We measured carotid artery intima-medial thickness, brachial-ankle pulse wave velocity, ankle-brachial pressure index, and the cardio-ankle vascular index. Log-transformed Kyn/Trp ratio was significantly correlated with log-transformed time on HD (ρ=0.28, PAnkle-brachial pressure index was lower in the second quartile (1.01±0.20), the third quartile (1.01±0.19), and the fourth quartile (1.03±0.15) compared with that in the first quartile (1.09±0.13) (PHemodialysis International © 2010 International Society for Hemodialysis.

  10. Leukotriene B4 levels in human atherosclerotic plaques and abdominal aortic aneurysms.

    Directory of Open Access Journals (Sweden)

    Pleunie van den Borne

    Full Text Available BACKGROUND: Leukotriene B4 (LTB4 has been associated with the initiation and progression of atherosclerosis and abdominal aortic aneurysm (AAA formation. However, associations of LTB4 levels with tissue characteristics and adverse clinical outcome of advanced atherosclerosis and AAA are scarcely studied. We hypothesized that LTB4 levels are associated with a vulnerable plaque phenotype and adverse clinical outcome. Furthermore, that LTB4 levels are associated with inflammatory AAA and adverse clinical outcome. METHODS: Atherosclerotic plaques and AAA specimens were selected from two independent databases for LTB4 measurements. Plaques were isolated during carotid endarterectomy from asymptomatic (n = 58 or symptomatic (n = 317 patients, classified prior to surgery. LTB4 levels were measured without prior lipid extraction and levels were corrected for protein content. LTB4 levels were related to plaque phenotype, baseline patient characteristics and clinical outcome within three years following surgery. Seven non-diseased mammary artery specimens served as controls. AAA specimens were isolated during open repair, classified as elective (n = 189, symptomatic (n = 29 or ruptured (n = 23. LTB4 levels were measured similar to the plaque measurements and were related to tissue characteristics, baseline patient characteristics and clinical outcome. Twenty-six non-diseased aortic specimens served as controls. RESULTS: LTB4 levels corrected for protein content were not significantly associated with histological characteristics specific for vulnerable plaques or inflammatory AAA as well as clinical presentation. Moreover, it could not predict secondary manifestations independently investigated in both databases. However, LTB4 levels were significantly lower in controls compared to plaque (p = 0.025 or AAA (p = 0.017. CONCLUSIONS: LTB4 levels were not associated with a vulnerable plaque phenotype or inflammatory AAA or clinical

  11. Chronic administration of mitochondrion-targeted peptide SS-31 prevents atherosclerotic development in ApoE knockout mice fed Western diet.

    Directory of Open Access Journals (Sweden)

    Meng Zhang

    Full Text Available Oxidative stress and inflammatory factors are deeply involved in progression of atherosclerosis. Mitochondrion-targeted peptide SS-31, selectively targeting to mitochondrial inner membrane reacting with cardiolipin, has been reported to inhibit ROS generation and mitigate inflammation. The present study was designed to investigate whether SS-31 could suppress the development of atherosclerosis in vivo.Male ApoE-/- mice (8 weeks old fed with Western diet were treated with normal saline or SS-31 (1 mg/kg/d or 3 mg/kg/d through subcutaneous injection for 12 weeks. Oil Red O staining was performed to evaluate area and sizes of the plaques. DHE staining and immunohistochemical staining of 8-OHDG was performed to assess the oxidative stress. The aorta ATP contents were assessed by the ATP bioluminescence assay kit. Immunohistochemical staining of CD68 and α-SMA and Masson's trichrome staining were performed to evaluate the composition of atherosclerotic plaque. Biochemical assays were performed to determine the protein level and activity of superoxide dismutase (SOD. The levels of CD36, LOX-1 and ABCA1 were immunohistochemically and biochemically determined to evaluate the cholesterol transport in aorta and peritoneal macrophages. Inflammatory factors, including ICAM-1, MCP-1, IL-6 and CRP in serum, were detected through ELISA.SS-31 administration reduced the area and sizes of western diet-induced atherosclerotic plaques and changed the composition of the plaques in ApoE-/- mice. Oxidative stress was suppressed, as evidenced by the reduced DHE stain, down-regulated 8-OHDG expression, and increased SOD activity after chronic SS-31 administration. Moreover, systemic inflammation was ameliorated as seen by decreasing serum ICAM-1, MCP-1, and IL-6 levels. Most importantly, SS-31 administration inhibited cholesterol influx by down-regulating expression of CD36 and LOX-1 to prevent lipid accumulation to further suppress the foam cell formation and

  12. Chronic administration of mitochondrion-targeted peptide SS-31 prevents atherosclerotic development in ApoE knockout mice fed Western diet.

    Science.gov (United States)

    Zhang, Meng; Zhao, Hongting; Cai, Jing; Li, Huihui; Wu, Qi; Qiao, Tong; Li, Kuanyu

    2017-01-01

    Oxidative stress and inflammatory factors are deeply involved in progression of atherosclerosis. Mitochondrion-targeted peptide SS-31, selectively targeting to mitochondrial inner membrane reacting with cardiolipin, has been reported to inhibit ROS generation and mitigate inflammation. The present study was designed to investigate whether SS-31 could suppress the development of atherosclerosis in vivo. Male ApoE-/- mice (8 weeks old) fed with Western diet were treated with normal saline or SS-31 (1 mg/kg/d or 3 mg/kg/d) through subcutaneous injection for 12 weeks. Oil Red O staining was performed to evaluate area and sizes of the plaques. DHE staining and immunohistochemical staining of 8-OHDG was performed to assess the oxidative stress. The aorta ATP contents were assessed by the ATP bioluminescence assay kit. Immunohistochemical staining of CD68 and α-SMA and Masson's trichrome staining were performed to evaluate the composition of atherosclerotic plaque. Biochemical assays were performed to determine the protein level and activity of superoxide dismutase (SOD). The levels of CD36, LOX-1 and ABCA1 were immunohistochemically and biochemically determined to evaluate the cholesterol transport in aorta and peritoneal macrophages. Inflammatory factors, including ICAM-1, MCP-1, IL-6 and CRP in serum, were detected through ELISA. SS-31 administration reduced the area and sizes of western diet-induced atherosclerotic plaques and changed the composition of the plaques in ApoE-/- mice. Oxidative stress was suppressed, as evidenced by the reduced DHE stain, down-regulated 8-OHDG expression, and increased SOD activity after chronic SS-31 administration. Moreover, systemic inflammation was ameliorated as seen by decreasing serum ICAM-1, MCP-1, and IL-6 levels. Most importantly, SS-31 administration inhibited cholesterol influx by down-regulating expression of CD36 and LOX-1 to prevent lipid accumulation to further suppress the foam cell formation and atherosclerotic

  13. Fatty acid amide hydrolase deficiency enhances intraplaque neutrophil recruitment in atherosclerotic mice

    NARCIS (Netherlands)

    Lenglet, Sébastien; Thomas, Aurélien; Soehnlein, Oliver; Montecucco, Fabrizio; Burger, Fabienne; Pelli, Graziano; Galan, Katia; Cravatt, Benjamin; Staub, Christian; Steffens, Sabine

    2013-01-01

    Endocannabinoid levels are elevated in human and mouse atherosclerosis, but their causal role is not well understood. Therefore, we studied the involvement of fatty acid amide hydrolase (FAAH) deficiency, the major enzyme responsible for endocannabinoid anandamide degradation, in atherosclerotic

  14. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

    NARCIS (Netherlands)

    Bot, M.; , van, Berkel T.J.C.

    2013-01-01

    Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by

  15. Serum Asymmetric Dimethylarginine, and Adiponectin as Predictors of Atherosclerotic Risk among Obese Egyptian Children

    Directory of Open Access Journals (Sweden)

    Enas R. Abdel Hameed

    2014-06-01

    CONCLUSIONS: Our results revealed that ADMA, Adiponectin and lipid profile can be considered as predictive biomarkers in prediction and prevention of atherosclerotic risk in the future among overweight and obese Egyptian children.

  16. Intravascular photoacoustic imaging of exogenously labeled atherosclerotic plaque through luminal blood

    Science.gov (United States)

    Yeager, Doug; Karpiouk, Andrei; Wang, Bo; Amirian, James; Sokolov, Konstantin; Smalling, Richard; Emelianov, Stanislav

    2012-10-01

    Combined intravascular ultrasound and intravascular photoacoustic (IVUS/IVPA) imaging has been previously established as a viable means for assessing atherosclerotic plaque morphological and compositional characteristics using both endogenous and exogenous contrast. In this study, IVUS/IVPA imaging of atherosclerotic rabbit aortas following systemic injection of gold nanorods (AUNRs) with peak absorbance within the tissue optical window is performed. Ex vivo imaging results reveal a high photoacoustic signal from localized AUNRs in regions with atherosclerotic plaques. Corresponding histological staining further confirms the preferential extravasation of AUNRs in atherosclerotic regions with compromised luminal endothelium and acute inflammation. The ability to detect AUNRs using combined IVUS and photoacoustic imaging in the presence of luminal saline and luminal blood is evaluated using both spectroscopic and single wavelength IVPA imaging techniques. Results demonstrate that AUNR detection within the arterial wall can be achieved using both methods, even in the case of imaging through luminal blood.

  17. International differences in dialysis mortality reflect background general population atherosclerotic cardiovascular mortality

    NARCIS (Netherlands)

    Yoshino, Maki; Kuhlmann, Martin K.; Kotanko, Peter; Greenwood, Roger N.; Pisoni, Ronald L.; Port, Friedrich K.; Jager, Kitty J.; Homel, Peter; Augustijn, Hans; de Charro, Frank T.; Collart, Frederic; Erek, Ekrem; Finne, Patrik; Garcia-Garcia, Guillermo; Grönhagen-Riska, Carola; Ioannidis, George A.; Ivis, Frank; Leivestad, Torbjorn; Løkkegaard, Hans; Lopot, Frantisek; Jin, Dong-Chan; Kramar, Reinhard; Nakao, Toshiyuki; Nandakumar, Mooppil; Ramirez, Sylvia; van der Sande, Frank M.; Schön, Staffan; Simpson, Keith; Walker, Rowan G.; Zaluska, Wojciech; Levin, Nathan W.

    2006-01-01

    Existing national, racial, and ethnic differences in dialysis patient mortality rates largely are unexplained. This study aimed to test the hypothesis that mortality rates related to atherosclerotic cardiovascular disease (ASCVD) in dialysis populations (DP) and in the background general populations

  18. Atherosclerotic renovascular disease and renal impairment : Can we predict the effect of intervention?

    NARCIS (Netherlands)

    Mui, Kwok-Wai; Woittiez, Arend-Jan; Navis, Gerjan

    Atherosclerotic renal artery stenosis (ARAS) is associated with hypertension, ischemic nephropathy, and high cardiovascular risk. We review the data on revascularization of the renal artery by percutaneous transluminal renal angioplasty (PTRA) and pharmacological therapy. In patients with severe

  19. Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration

    NARCIS (Netherlands)

    van der Valk, Fleur M.; van Wijk, Diederik F.; Lobatto, Mark E.; Verberne, Hein J.; Storm, G|info:eu-repo/dai/nl/073356328; Willems, Martine C M; Legemate, Dink A.; Nederveen, Aart J.; Calcagno, Claudia; Mani, Venkatesh; Ramachandran, Sarayu; Paridaans, Maarten P M; Otten, Maarten J.; Dallinga-Thie, Geesje M.; Fayad, Zahi A.; Nieuwdorp, Max; Schulte, Dominik M.; Metselaar, Josbert M.|info:eu-repo/dai/nl/244207690; Mulder, Willem J M; Stroes, Erik S.

    2015-01-01

    Drug delivery to atherosclerotic plaques via liposomal nanoparticles may improve therapeutic agents' risk-benefit ratios. Our paper details the first clinical studies of a liposomal nanoparticle encapsulating prednisolone (LN-PLP) in atherosclerosis. First, PLP's liposomal encapsulation improved its

  20. Compressive mechanical properties of atherosclerotic plaques - Indentation test to characterise the local anisotropic behaviour

    NARCIS (Netherlands)

    C.-K. Chai (Chen-Ket); L. Speelman (Lambert); C.W.J. Oomens (Cees); F.P.T. Baaijens (Frank)

    2014-01-01

    textabstractAccurate material models and associated parameters of atherosclerotic plaques are crucial for reliable biomechanical plaque prediction models. These biomechanical models have the potential to increase our understanding of plaque progression and failure, possibly improving risk assessment

  1. A selective ACAT-1 inhibitor, K-604, suppresses fatty streak lesions in fat-fed hamsters without affecting plasma cholesterol levels.

    Science.gov (United States)

    Ikenoya, Mami; Yoshinaka, Yasunobu; Kobayashi, Hideyuki; Kawamine, Katsumi; Shibuya, Kimiyuki; Sato, Fumiyasu; Sawanobori, Kimio; Watanabe, Takuya; Miyazaki, Akira

    2007-04-01

    Acyl-coenzyme A:cholesterol O-acyltransferase-1 (ACAT-1), a major ACAT isozyme in macrophages, plays an essential role in foam cell formation in atherosclerotic lesions. However, whether pharmacological inhibition of macrophage ACAT-1 causes exacerbation or suppression of atherosclerosis is controversial. We developed and characterized a novel ACAT inhibitor, K-604. The IC(50) values of K-604 for human ACAT-1 and ACAT-2 were 0.45 and 102.85 micromol/L, respectively, indicating that K-604 is 229-fold more selective for ACAT-1. Kinetic analysis indicated that the inhibition was competitive with respect to oleoyl-coenzyme A with a K(i) value of 0.378 micromol/L. Exposure of human monocyte-derived macrophages to K-604 inhibited cholesterol esterification with IC(50) of 68.0 nmol/L. Furthermore, cholesterol efflux from THP-1 macrophages to HDL(3) or apolipoprotein A-I was enhanced by K-604. Interestingly, administration of K-604 to F1B hamsters on a high-fat diet at a dose of >or=1mg/kg suppressed fatty streak lesions without affecting plasma cholesterol levels. K-604, a potent and selective inhibitor of ACAT-1, suppressed the development of atherosclerosis in an animal model without affecting plasma cholesterol levels, providing direct evidence that pharmacological inhibition of ACAT-1 in the arterial walls leads to suppression of atherosclerosis.

  2. Lesion activity assessment

    DEFF Research Database (Denmark)

    Ekstrand, K R; Zero, D T; Martignon, S

    2009-01-01

    of predictors increases the accuracy of lesion activity prediction for both primary coronal and root lesions. Three surrogate methods have been used for evaluating lesion activity (construct validity); all have disadvantages. If construct validity is accepted as a 'gold standard', it is possible to assess......This chapter focusses on the probability of a caries lesion detected during a clinical examination being active (progressing) or arrested. Visual and tactile methods to assess primary coronal lesions and primary root lesions are considered. The evidence level is rated as low (R...... in response to cariogenic plaque as well as lesion arrest. Based on this understanding, different clinical scoring systems have been developed to assess the severity/depth and activity of lesions. A recent system has been devised by the International Caries Detection and Assessment System Committee...

  3. Skin lesion removal

    Science.gov (United States)

    Shave excision - skin; Excision of skin lesions - benign; Skin lesion removal - benign; Cryosurgery - skin, benign; BCC - removal; Basal cell cancer - removal; Actinic keratosis - removal; Wart - removal; Squamous cell - removal; ...

  4. Skin lesion of blastomycosis

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000865.htm Skin lesion of blastomycosis To use the sharing features on this page, please enable JavaScript. A skin lesion of blastomycosis is a symptom of an infection ...

  5. Skin lesion aspiration

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003451.htm Skin lesion aspiration To use the sharing features on this page, please enable JavaScript. Skin lesion aspiration is the withdrawal of fluid from a ...

  6. Symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) with concurrent contralateral vertebral atherosclerotic diseases in 88 patients treated with the intracranial stenting

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zi-Liang [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China); Gao, Bu-Lang [Department of Medical Research Shijiazhuang First Hospital, Hebei Medical University (China); Li, Tian-Xiao, E-mail: litianxiaod@163.com [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China); Cai, Dong-Yang; Zhu, Liang-Fu; Bai, Wei-Xing; Xue, Jiang-Yu; Li, Zhao-Shuo [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China)

    2015-09-15

    Highlights: • Symptomatic vertebral artery stenosis can be treated with intracranial stenting. • Stenting for intracranial vertebral artery stenosis is safe and effective. • Stenting for intracranial vertebral artery stenosis can prevent long-term stroke. - Abstract: Purpose: To investigate the safety, effect and instent restenosis rate of Wingspan stenting in treating patients with intracranial vertebral artery atherosclerotic stenosis (70–99%) concurrent with contralateral vertebral artery atherosclerotic diseases. Materials and methods: Eighty-eight patients with severe symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) combined with contralateral vertebral artery atherosclerotic diseases were treated with the Wingpsan stent. All the baseline, cerebral angiography, success rate, perioperative complications, clinical and imaging follow-up data were prospectively analyzed. Results: The success rate of stenting was 100%, and the mean stenotic rate was reduced from prestenting (84.9 ± 6.8)% to poststenting (17.2 ± 5.9)%. The perioperative stroke rate was 1.1%. Among eighty patients (90.9%) with clinical follow-up 8-62 months (mean 29.3 ± 17.2) poststenting, five (6.3%) had posterior circulation TIA only, three (3.8%) had mild stroke in the posterior circulation but recovered completely, and another five patients greater than 70 years old died of non-ischemic stroke. Imaging follow-up in 46 patients (52.3%) 5–54 months (mean 9.9 ± 9.9) following stenting revealed instent restenosis in 12 patients (26.1%) including 7 (58.3%) symptomatic restenosis. Age and residual stenosis were the two factors to significantly (P < 0.05) affect instent restenosis. Conclusion: Wingspan stenting in the intracranial vertebral artery atherosclerotic stenosis combined with contralateral vertebral artery atherosclerotic diseases has a low perioperative stroke rate and a good preventive effect on long-term ischemic stroke, but the instent restenosis

  7. Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: Preliminary study of plaque progression

    OpenAIRE

    Assemat, P.; Siu, K.K.; Armitage, J.A.; Hokke, S.N.; Dart, A; Chin-Dusting, J; Hourigan, K.

    2014-01-01

    Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical mode...

  8. Moderate overweight is beneficial and severe obesity detrimental for patients with documented atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Azimi, Aziza; Charlot, Mette Gitz; Torp-Pedersen, Christian Tobias

    2013-01-01

    Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease.......Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease....

  9. Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl-Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct Formation.

    Science.gov (United States)

    Berger, Florence D; Sturla, Shana J; Kung, Ryan W; Montina, Tony; Wetmore, Stacey D; Manderville, Richard A

    2018-01-16

    Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently to the C8-site of 2'-deoxyguanosine (dG) to afford C8-dG adducts. The most studied C8-dG adducts are formed from arylamines and contain a N-linkage separating the dG from the C8-aryl moiety. Other carcinogenic species result in direct aryl ring attachment to the dG moiety, resulting in C-linked adducts. The resulting C-linked adducts have reduced conformational flexibility compared to the corresponding N-linked C8-dG adducts, which can alter their orientation in the DNA duplex. Described herein are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG) that has been incorporated into the reiterated G3-postion of the 12-mer NarI sequence and those containing other 5'-flanking nucleobases. FBP-dG displays a strong preference for adopting a syn conformation in the fully paired NarI duplex to produce an intercalated structure that exhibits stacking interactions between the C-linked biphenyl and the flanking bases. FBP-dG is also shown to significantly stabilize the slippage mutagenic intermediate (SMI) duplex containing the lesion and 5'-flanking base within a 2-base bulge. FBP-dG exhibits fluorescence sensitivity to SMI duplex formation that can readily distinguish it from the fully paired duplex. Molecular dynamics simulations and optical spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict increased rigidity of the biphenyl in the syn conformation. The greater propensity to generate the promutagenic syn conformation for the C-linked FBP-dG adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests greater mutagenicity for the C-linked analogue. These results highlight the effect of the adduct linkage type on the conformational properties of adducted DNA. The turn-on emission response of FBP-dG in the SMI duplex may be a powerful tool for monitoring SMI formation in the

  10. Genistein supplementation inhibits atherosclerosis with stabilization of the lesions in hypercholesterolemic rabbits.

    Science.gov (United States)

    Lee, Choong-Sik; Kwon, Su-Jin; Na, Sun-Young; Lim, Seung-Pyung; Lee, Jung-Hee

    2004-10-01

    The effect of genistein on aortic atherosclerosis was studied by immunohistochemistry with RAM-11 and HHF-35 antibodies and western blotting for matrix metalloproteinase-3 (MMP-3) in New Zealand White rabbits. After provocation of atherosclerosis with hyperlipidemic diet, the rabbits were divided as hyperlipidemic diet group (HD), normal diet group (ND) and hyperlipidemic plus genistein diet group (HD+genistein) for 4 and half months. The average cross sectional area of atherosclerotic lesion was 0.269 mm2 after provocation. The lesion was progressed by continuous hyperlipidemic diet (10.06 mm2) but was increased mildly by genistein (0.997 mm2), and decreased by normal diet (0.228 mm2). The ratio of macrophages to smooth muscle cells in the lesion was not changed by genistein supplementation. The western blotting showed reduction of MMP-3 expression in HD+genistein and ND groups than HD group. The inhibition of atherogenesis by genistein was might be due to improve the endothelial dysfunction rather than direct action on macrophages and/or smooth muscle cells in the lesion, since endothelial dysfunction by lipid peroxidation was the main atherogenic factor in the hypercholesterolemic rabbits. The genistein supplementation also suggests that it helps the stabilization of the atherosclerotic lesion by inhibition of MMP-3 expression.

  11. Lysophosphatidic acid directly induces macrophage-derived foam cell formation by blocking the expression of SRBI.

    Science.gov (United States)

    Chen, Linmu; Zhang, Jun; Deng, Xiao; Liu, Yan; Yang, Xi; Wu, Qiong; Yu, Chao

    2017-09-23

    The leading cause of morbidity and mortality is the result of cardiovascular disease, mainly atherosclerosis. The formation of macrophage foam cells by ingesting ox-LDL and focal retention in the subendothelial space are the hallmarks of the early atherosclerotic lesion. Lysophosphatidic acid (LPA), which is a low-molecular weight lysophospholipid enriched in oxidized LDL, exerts a range of effects on the cardiovascular system. Previous reports show that LPA increases the uptake of ox-LDL to promote the formation of foam cells. However, as the most active component of ox-LDL, there is no report showing whether LPA directly affects foam cell formation. The aim of this study was to investigate the effects of LPA on foam cell formation, as well as to elucidate the underlying mechanism. Oil red O staining and a Cholesterol/cholesteryl ester quantitation assay were used to evaluate foam cell formation in Raw264.7 macrophage cells. We utilized a Western blot and RT-PCR to investigate the relationship between LPA receptors and lipid transport related proteins. We found that LPA promoted foam cell formation, using 200 μM for 24 h. Meanwhile, the expression of the Scavenger receptor BI (SRBI), which promotes the efflux of free cholesterol, was decreased. Furthermore, the LPA 1/3 receptor antagonist Ki16425 significantly abolished the LPA effects, indicating that LPA 1/3 was involved in the foam cell formation and SRBI expression induced by LPA. Additionally, the LPA-induced foam cell formation was blocked with an AKT inhibitor. Our results suggest that LPA-enhanced foam cell formation is mediated by LPA 1/3 -AKT activation and subsequent SRBI expression. Copyright © 2017. Published by Elsevier Inc.

  12. Dihydrocapsaicin Attenuates Plaque Formation through a PPARγ/LXRα Pathway in apoE(-/- Mice Fed a High-Fat/High-Cholesterol Diet.

    Directory of Open Access Journals (Sweden)

    Yan-Wei Hu

    Full Text Available Atherosclerosis is a chronic inflammatory disease and represents the major cause of cardiovascular morbidity and mortality. There is evidence that dihydrocapsaicin (DHC can exert multiple pharmacological and physiological effects. Here, we explored the effect of DHC in atherosclerotic plaque progression in apoE(-/- mice fed a high-fat/high-cholesterol diet.apoE(-/- mice were randomly divided into two groups and fed a high-fat/high-cholesterol diet with or without DHC for 12 weeks. We demonstrated that cellular cholesterol content was significantly decreased while apoA1-mediated cholesterol efflux was significantly increased following treatment with DHC in THP-1 macrophage-derived foam cells. We also observed that plasma levels of TG, LDL-C, VLDL-C, IL-1β, IL-6, TNF-α and CRP were markedly decreased while plasma levels of apoA1 and HDL-C were significantly increased, and consistent with this, atherosclerotic lesion development was significantly inhibited by DHC treatment of apoE(-/- mice fed a high-fat/high-cholesterol diet. Moreover, treatment with both LXRα siRNA and PPARγ siRNA made the up-regulation of DHC on ABCA1, ABCG1, ABCG5, SR-B1, NPC1, CD36, LDLR, HMGCR, apoA1 and apoE expression notably abolished while made the down-regulation of DHC on SRA1 expression markedly compensated. And treatment with PPARγ siRNA made the DHC-induced up-regulation of LXRα expression notably abolished while treatment with LXRα siRNA had no effect on DHC-induced PPARγ expression.These observations provide direct evidence that DHC can significantly decrease atherosclerotic plaque formation involving in a PPARγ/LXRα pathway and thus DHC may represent a promising candidate for a therapeutic agent for the treatment or prevention of atherosclerosis.

  13. Tumefactive demyelinating lesions

    Energy Technology Data Exchange (ETDEWEB)

    Dagher, A.P. [Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States). Div. of Neuroradiology; Smirniotopoulos, J. [Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States). Div. of Neuroradiology]|[Armed Forces Inst. of Pathology, Washington, DC (United States). Dept. of Radiological Pathology

    1996-08-01

    We studied 21 cases of pathologically confirmed tumefactive demyelinating lesions and reviewed the spectrum of tumefactive demyelinating lesions in the literature. Radiological features and clinical data were reviewed to characterize the lesions as consistent with a known demyelinating disease, most notably multiple sclerosis. Atypical clinical or radiological features (other than tumefaction) were noted. Most lesions were part of a clinical and/or radiological picture consistent with multiple sclerosis. No case strongly suggestive of variants or related diseases, such as Schilder`s disease or Balo`s concentric sclerosis, were found. There was one case suggestive of acute disseminated encephalomyelitis. Features which help distinguish the lesions from tumour are discussed. (orig.)

  14. Paramagnetic Manganese in the Atherosclerotic Plaque of Carotid Arteries

    Directory of Open Access Journals (Sweden)

    Yury Chelyshev

    2016-01-01

    Full Text Available The search for adequate markers of atherosclerotic plaque (AP instability in the context of assessment of the ischemic stroke risk in patients with atherosclerosis of the carotid arteries as well as for solid physical and chemical factors that are connected with the AP stability is extremely important. We investigate the inner lining of the carotid artery specimens from the male patients with atherosclerosis (27 patients, 42–64 years old obtained during carotid endarterectomy by using different analytical tools including ultrasound angiography, X-ray analysis, immunological, histochemical analyses, and high-field (3.4 T pulse electron paramagnetic resonance (EPR at 94 GHz. No correlation between the stable and unstable APs in the sense of the calcification is revealed. In all of the investigated samples, the EPR spectra of manganese, namely, Mn2+ ions, are registered. Spectral and relaxation characteristics of Mn2+ ions are close to those obtained for the synthetic (nano hydroxyapatite species but differ from each other for stable and unstable APs. This demonstrates that AP stability could be specified by the molecular organization of their hydroxyapatite components. The origin of the obtained differences and the possibility of using EPR of Mn2+ as an AP stability marker are discussed.

  15. Anti-atherosclerotic effect of hesperidin in LDLr-/-mice and its possible mechanism.

    Science.gov (United States)

    Sun, Ye-Zi; Chen, Jian-Fei; Shen, Li-Min; Zhou, Ji; Wang, Cui-Fang

    2017-11-15

    Hesperidin, a citrus bioflavonoid, exerts numerous pharmacological activities. However, its protective effect against atherosclerosis in vivo remains poorly understood. In the present study, we aimed to observe the effects of hesperidin on high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient (LDLr -/- ) mice. After 12 weeks of treatment, the animals were sacrificed. The blood samples were collected for further analysis. Mouse peritoneal macrophages were collected. Hepatic lipid content, quantification of atherosclerosis, assessment of oxidative stress and inflammation, gene expressions were performed on liver and aorta samples. The data showed that hesperidin ameliorated HFD-induced weight gain, improved insulin resistance and ameliorated hyperlipidemia. Hesperidin suppressed HFD-induced hepatic steatosis, atherosclerotic plaque area and macrophage foam cell formation. Further study showed that hesperidin down-regulated expressions of acetyl coenzyme A carboxylase alpha (ACCα) and fatty acid synthase (FAS) which are two key enzymes in fatty acid and triglyceride synthesis in liver; and upregulated expression of hepatic ATP-binding cassette transporters G8 (ABCG8), macrophage ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1) which are transporters involved in the process of reverse cholesterol transport. Hesperidin also reduced oxidative stress by normalizing activities of antioxidant enzymes and inflammation in HFD-fed LDLr -/- mice. These findings suggest that hesperidin reduced atherosclerosis via its pleiotropic effects, including improvement of insulin resistance, amelioration of lipid profiles, inhibition of macrophage foam cell formation, anti-oxidative effect and anti-inflammatory action. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Detection of coronary atherosclerotic plaques with superficial proteoglycans and foam cells using real-time intrinsic fluorescence spectroscopy.

    Science.gov (United States)

    Angheloiu, George O; Haka, Abigail S; Georgakoudi, Irene; Arendt, Joseph; Müller, Markus G; Scepanovic, Obrad R; Evanko, Stephen P; Wight, Thomas N; Mukherjee, Prasun; Waldeck, David H; Dasari, Ramachandra R; Fitzmaurice, Maryann; Kramer, John R; Feld, Michael S

    2011-03-01

    The protein components of low-density lipoprotein (LDL), oxidized LDL and proteoglycans such as versican contain tryptophan, an amino acid with characteristic fluorescence features at 308 nm excitation wavelength. We hypothesize that intrinsic fluorescence spectroscopy at 308 nm excitation wavelength IFS308, a method suitable for clinical use, can identify coronary artery lesions with superficial foam cells (SFCs) and/or proteoglycans. We subjected 119 human coronary artery specimens to in vitro fluorescence and reflectance spectroscopy. We used 5 basis spectra to model IFS308, and extracted their contributions to each individual IFS308 spectrum. A diagnostic algorithm using the contributions of Total Tryptophan and fibrous cap to IFS308 was built to identify specimens with SFCs and/or proteoglycans in their top 50 μm. We detected SFCs and/or proteoglycans, such as versican or the glycosaminoglycan hyaluronan, in 24 fibrous cap atheromas or pathologic intimal thickening (PIT) lesions. An algorithm using the contributions of Total Tryptophan and fibrous cap to IFS308 was able to identify these segments with 92% sensitivity and 80% specificity. We were able to establish a set of characteristic LDL, oxidized LDL, versican and hyaluronan fluorescence spectra, ready to be used for real-time diagnosis. The IFS(308) technique detects SFCs and/or proteoglycans in fibrous cap atheromas and PIT lesions. SFCs and proteoglycans are histological markers of vulnerable plaques, and this study is a step further in developing an invasive clinical tool to detect the vulnerable atherosclerotic plaque. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Fibulin-2 is present in murine vascular lesions and is important for smooth muscle cell migration

    DEFF Research Database (Denmark)

    Ström, A.; Olin, A. I.; Aspberg, A.

    2006-01-01

    Objective: The vascular extracellular matrix (ECM) can affect smooth muscle cell (SMC) adhesion, migration and proliferation-events that are important during the atherosclerotic process. Fibulin-2 is a member of the ECM protein family of fibulins and has been found to cross-link versican/hyaluron......Objective: The vascular extracellular matrix (ECM) can affect smooth muscle cell (SMC) adhesion, migration and proliferation-events that are important during the atherosclerotic process. Fibulin-2 is a member of the ECM protein family of fibulins and has been found to cross-link versican...... migration was studied in the presence of two inhibiting peptides (FN III 3-5 and aggrecan C-type lectin-like domain). Results: Fibulin-2 is expressed in SMC rich regions of atherosclerotic lesions where it colocalises with versican and hyaluronan. It is also present in injury-induced vascular lesions...... and is upregulated during SMC phenotypic modulation in cell culture. Moreover, treatments with peptides that block the interaction between versican and fibulin-2 inhibit SMC migration in vitro. Conclusions: Fibulin-2 can be produced by SMC as a response to injury and may participate in the ECM organisation...

  18. Structural Remodeling of Sympathetic Innervation in Atherosclerotic Blood Vessels: Role of Atherosclerotic Disease Progression and Chronic Social Stress.

    Science.gov (United States)

    Noller, Crystal M; Mendez, Armando J; Szeto, Angela; Boulina, Marcia; Llabre, Maria M; Zaias, Julia; Schneiderman, Neil; McCabe, Philip M

    2017-01-01

    The sympathetic nervous system (SNS) can undergo dramatic structural plasticity in response to behavioral factors and/or the presence of disease, leading to SNS hyperinnervation of peripheral tissues. The SNS has been proposed as an important mediator between stressful behavior and the progression of atherosclerosis in the vasculature. The present study examined whether structural remodeling of the SNS occurs in the vasculature in a genetically hyperlipidemic animal model of atherosclerosis, the Watanabe heritable hyperlipidemic rabbit (WHHL; relative to normolipidemic New Zealand white rabbits [NZW]), and whether SNS plasticity is driven by the progression of disease and/or by stressful social behavior. WHHL and NZW rabbits were assigned to an unstable or stable social environment for 4 months. Aortic atherosclerosis was assessed and SNS aortic innervation quantified using immunofluorescent microscopy. Numerous SNS varicosities were observed throughout the aorta in WHHLs and NZWs, extending into the vascular media and intima, an innervation pattern not previously reported. WHHLs exhibited significantly greater innervation than NZWs (F(1,41) = 55.3, p Social environment did not influence innervation in NZWs (aortic arch: p = .078, thoracic aorta: p = .34) or WHHLs (arch: p = .97, thoracic: p = .61). The findings suggest that hyperinnervation is driven largely by the progression of disease rather than social environment. SNS innervation patterns observed in atherosclerotic human and mouse aortas were consistent with the rabbit, suggesting that SNS hyperinnervation of the diseased vessel wall is a general feature across mammalian species.

  19. The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine

    Directory of Open Access Journals (Sweden)

    Saskia J. H. Brinkmann

    2015-05-01

    Full Text Available Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS and thereby nitric oxide (NO, respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9, standard rabbit chow plus atorvastatin (group S, n = 8, standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8 or standard rabbit chow (group C, n = 9 as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.

  20. Antiatherogenicity of extra virgin olive oil and its enrichment with green tea polyphenols in the atherosclerotic apolipoprotein-E-deficient mice: enhanced macrophage cholesterol efflux.

    Science.gov (United States)

    Rosenblat, Mira; Volkova, Nina; Coleman, Raymond; Almagor, Yaron; Aviram, Michael

    2008-08-01

    The antiatherogenic properties of extra virgin olive oil (EVOO) enriched with green tea polyphenols (GTPPs; hereafter called EVOO-GTPP), in comparison to EVOO, were studied in the atherosclerotic apolipoprotein-E-deficient (E0) mice. E0 mice (eight mice in each group) consumed EVOO or EVOO-GTPP (7 microl/mouse/day, for 2 months) by gavage feeding. The placebo group received only water. At the end of the study, blood samples, peritoneal macrophages and aortas were collected. Consumption of EVOO or EVOO-GTPP resulted in a minimal increase in serum total and high-density lipoprotein (HDL) cholesterol levels (by 12%) and in serum paraoxonase 1 activity (by 6% and 10%). EVOO-GTPP (but not EVOO) decreased the susceptibility of the mouse serum to AAPH-induced lipid peroxidation (by 18%), as compared to the placebo-treated mice. The major effect of both EVOO and EVOO-GTPP consumption was on HDL-mediated macrophage cholesterol efflux. Consumption of EVOO stimulated cholesterol efflux rate from mouse peritoneal macrophages (MPMs) by 42%, while EVOO-GTPP increased it by as much as 139%, as compared to MPMs from placebo-treated mice. Finally, the atherosclerotic lesion size of mice was significantly reduced by 11% or 20%, after consumption of EVOO or EVOO-GTPP, respectively. We thus conclude that EVOO possesses beneficial antiatherogenic effects, and its enrichment with GTPPs further improved these effects, leading to the attenuation of atherosclerosis development.

  1. A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

    2014-01-01

    When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower l...... suggest that cholesterol matrix formation may play a pathogenic role in atherosclerotic inflammation, and they indicate a mechanism by which bacteria and/or bacterial products may play a role in processes leading to arteriosclerosis....

  2. A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

    2014-01-01

    When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower...... suggest that cholesterol matrix formation may play a pathogenic role in atherosclerotic inflammation, and they indicate a mechanism by which bacteria and/or bacterial products may play a role in processes leading to arteriosclerosis....

  3. Murine atherosclerotic plaque imaging with the USPIO Ferumoxtran-10.

    Science.gov (United States)

    Klug, Gert; Kampf, Thomas; Ziener, Christan; Parczyk, Marco; Bauer, Elizabeth; Herold, Volker; Rommel, Eberhard; Jakob, Peter Michael; Bauer, Wolfgang Rudolf

    2009-01-01

    In this study we intended to image plaque inflammation in a murine model of atherosclerosis with MRI and Ferumoxtran-10 (Sinerem, Guerbet, France). 8 apoE-/- mice were injected 500 micromol Fe/kg or 1000 micromol Fe/kg Ferumoxtran-10. 2 apoE-/- mice were injected NaCl. After a post-contrast time of 24 to 336 hours the mice were scarificed and the aortas were imaged ex vivo. All measurements were performed on a 17.6 Tesla Bruker AVANCE 750WB MR scanner (Bruker, Germany). Spin-echo sequences and gradient-echo sequences with variable TE were performed and T2* maps were generated. Prussian-blue and hematoxilin-eosin histology were obtained afterwards and iron-uptake was quantified by counting iron positive areas. 2 apoE-/- mice were imaged in vivo before and 48 hours after 1000 micromol Fe/kg. Atheroma iron uptake was not elevated after 24 hours compared to controls. 48 hours after 1000 micromol Fe/kg but not 500 micromol Fe/kg histology revealed a 1.3- fold increase in plaque iron content compared to NaCl injected mice. Normalized T2*-times decreased from 0.86+/-0.02 in controls to 0.66+/-0.15 after a dose of 500 micromol Fe/ml and 0.59+/-0.14 in mice injected with 1000 micromol Fe/Kg (p=0.038). These results translated into a mean of 122% increase in CNR, as measured by in vivo MRI. We have demonstrated that Ferumoxtran-10 is taken up by atherosclerotic plaques in untreated apoE-/- mice and this alters plaque signal properties.

  4. The Natural Compound Dansameum Reduces foam Cell Formation by Downregulating CD36 and Peroxisome Proliferator-activated Receptor-gamma; Expression.

    Science.gov (United States)

    Park, Kang-Seo; Ahn, Sang Hyun; Lee, Kang Pa; Park, Sun-Young; Cheon, Jin Hong; Choi, Jun-Yong; Kim, Kibong

    2018-01-01

    Atherosclerosis-induced vascular disorders are major causes of death in most western countries. During the development of atherosclerotic lesions, foam cell formation is essential and formed through the expression of CD36 and the peroxisome proliferator-activated receptor gamma (PPAR-γ). To investigate whether dansameum extract (DSE) could show anti-atherosclerotic effect through down-regulating cellular redox state including CD36 and PARP-γ expression in oxidative low-density lipoprotein (oxLDL)-treated RAW264.7 cells and on differentiated foam cells in ApoE Knockout (ApoE-/-) mice. The Korean polyherbal medicine DSE was prepared from three plants in the following proportions: 40 g of Salvia miltiorrhiza root, 4 g of Amomumxanthioides fruit, and 4 g of Santalum album lignum. The immunohistochemistry and reverse transcription-polymerase chain reaction was used for analysis of protein and mRNA involved in foam cell formation. We first showed that effects of DSE on foam cell formation in both oxLDL-induced RAW264.7 cells and in blood vessels from apolipoprotein E deficientApoE-/- mice with high fat diet-fed. DSE treatment significantly reduced the expression of CD36 and PPAR-γ in oxLDL-stimulated RAW264.7 cells and ApoE-/-mice, in the latter case by regulating heme oxygenase-1. Furthermore, DSE treatment also reduced cellular lipid content in vitro and in vivo experiments. Our data suggest that DSE may have anti-atherosclerotic properties through regulating foam cell formation. Dansameum extract (DSE) Regulates the expression of CD36 and peroxisome proliferator-activated receptor gamma in oxidative low-density lipoprotein-stimulated RAW264.7 Cells and ApoE Knockout (ApoE Knockout [ApoE-/-]) miceDSE Regulates Cholesterol Levels in the Serum of ApoE-deficient (ApoE-/-) miceDSE Reduced the Formation of Foam Cells by Regulating heme oxygenase-1 in ApoE-/- mice with high fat diet-fed. Abbreviations used: DSE: Dansameum extract, PPAR-γ: Peroxisome proliferator

  5. Uterine vascular lesions.

    Science.gov (United States)

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management.

  6. The content of copper and zinc in human ulcered atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Radak Đorđe

    2004-01-01

    Full Text Available INTRODUCTION Copper and zinc have significant antiatherogenic effect influencing activity of antioxidant enzyms (giutathion-peroxidase i superoxid-dismutase, mechanism of apoptosis and other mechanisms. Few studies showed increased copper and zinc concentration in atherosclerotic plaque in comparison to normal vascular tissue. AIM The aim of the study was to compare copper and zinc concentrations in carotid artery tissue without significant atherosclerotic changes and human ulcered atherosclerotic plaque. MATERIAL AND METHODS Study was conducted on 66 patients. Carotid endarterectomy due to the significant carotid atherosclerotic changes with cerebrovascular disorders was performed in 54 patients (81.8%. Control group consisted of 12 patients (18.2% without carotid atherosclerotic changes operated due to the symptomatic kinking and coiling of carotid artery. Operated group consisted of 38 man (62.96% and 16 woman (37.04%. Control group had the same number of patients: six men (50% and six women (50%. Preoperatively, all patients were examined by vascular surgeon, neurologist and cardiologist. Duplex sonografy of carotid and vertebral arteries was performed by Aloca DSD 630 ultrasound with mechanical and linear transducer 7.7 MHz. Indication for surgical treatment was obtained according to non-invasive diagnostic protocol and neurological symptoms. Copper and zinc concentration in human ulcered atherosclerotic plaque and carotid artery segment were estimated by spectophotometry (Varian AA-5. RESULTS Average age of our patients was 59.8±8.1 years. For males average age was 76.1 ±9.8 years. And for females 42.4±5.8 years. In group with carotid endarterectomy female patients were significantly younger than male patients (p<0.01. In group with carotid endarterectomy clinically determined neurological disorders were found in 47 patients (87.03%-35 male (74.47% and 12 female patients (25.53%. Regarding risk factors for cardiovascular diseases, no

  7. Diagnosis and management of atherosclerotic cardiovascular disease in chronic kidney disease: a review.

    Science.gov (United States)

    Mathew, Roy O; Bangalore, Sripal; Lavelle, Michael P; Pellikka, Patricia A; Sidhu, Mandeep S; Boden, William E; Asif, Arif

    2017-04-01

    Patients with chronic kidney disease (CKD) have a high prevalence of atherosclerotic cardiovascular disease, likely reflecting the presence of traditional risk factors. A greater distinguishing feature of atherosclerotic cardiovascular disease in CKD is the severity of the disease, which is reflective of an increase in inflammatory mediators and vascular calcification secondary to hyperparathyroidism of renal origin that are unique to patients with CKD. Additional components of atherosclerotic cardiovascular disease that are prominent in patients with CKD include microvascular disease and myocardial fibrosis. Therapeutic interventions that minimize cardiovascular events related to atherosclerotic cardiovascular disease in patients with CKD, as determined by well-designed clinical trials, are limited to statins. Data are lacking regarding other available therapeutic measures primarily due to exclusion of patients with CKD from major trials studying cardiovascular disease. Data from well-designed randomized controlled trials are needed to guide clinicians who care for this high-risk population in the management of atherosclerotic cardiovascular disease to improve clinical outcomes. Published by Elsevier Inc.

  8. Decreased cathepsin K levels in human atherosclerotic plaques are associated with plaque instability.

    Science.gov (United States)

    Zhao, Huiying; Qin, Xiujiao; Wang, Shuai; Sun, Xiwei; Dong, Bin

    2017-10-01

    Investigating the determinants and dynamics of atherosclerotic plaque instability is a key area of current cardiovascular research. Extracellular matrix degradation from excessive proteolysis induced by enzymes such as cathepsin K (Cat K) is implicated in the pathogenesis of unstable plaques. The current study assessed the expression of Cat K in human unstable atherosclerotic plaques. Specimens of popliteal arteries with atherosclerotic plaques were classified as stable (K and cystatin C (Cys C) were assessed by immunohistochemical examination and levels of Cat K mRNA were detected by semi-quantitative reverse transcriptase polymerase chain reaction. Morphological changes including a larger lipid core, endothelial proliferation with foam cells and destruction of internal elastic lamina were observed in unstable atherosclerotic plaques. In unstable plaques, the expression of Cat K protein and mRNA was upregulated, whereas Cys C protein expression was downregulated. The interplay between Cat K and Cys C may underlie the progression of plaques from stable to unstable and the current study indicated that Cat K and Cys C are potential targets for preventing and treating vulnerable atherosclerotic plaque ruptures.

  9. In vivo distribution of single chain variable fragment (scFv) against atherothrombotic oxidized LDL/β2-glycoprotein I complexes into atherosclerotic plaques of WHHL rabbits: Implication for clinical PET imaging.

    Science.gov (United States)

    Sasaki, Takanori; Kobayashi, Kazuko; Kita, Shoichi; Kojima, Kazuo; Hirano, Hiroyuki; Shen, Lianhua; Takenaka, Fumiaki; Kumon, Hiromi; Matsuura, Eiji

    2017-02-01

    Oxidized LDL (oxLDL) can exist as a complex with β2-glycoprotein I (β2GPI) in plasma/serum of patients with non-autoimmune atherosclerotic disease or antiphospholipid syndrome (APS). Nonetheless, direct in vivo evidence supporting the pathophysiological involvement of oxLDL/β2GPI complexes and specific autoantibody against the complexes in developing atherothrombosis has yet been established. In the present study, we demonstrated in vivo distribution of single chain variable fragment of IgG anti-oxLDL/β2GPI complexes (3H3-scFv) in Watanabe heritable hyperlipidemic (WHHL) rabbits by PET/CT imaging. An antibody-based PET probe, 64Cu-3H3-scFv, was established, and WHHL rabbits were applied for a non-autoimmune atherosclerotic model to demonstrate in vivo distribution of the probe. 3H3-scFv has exhibits specificity towards β2GPI complexed with oxLDL but neither a free form of β2GPI nor oxLDL alone. Post-intravenous administration of 64Cu-3H3-scFv into WHHL rabbits has demonstrated a non-invasive approach for in vivo visualization of atherosclerotic lesion. The imaging probe achieved ideal blood clearance and distribution for optimal imaging capacity in 24h, significantly shorter than that of an intact IgG-based imaging probe. 64Cu-3H3-scFv targeted on atherosclerotic plaques in aortas of WHHL rabbits where extensive accumulation of lipid deposits was observed by lipid staining and autoradiography. The accumulation of 64Cu-3H3-scFv in aortic segments of WHHL rabbits was 2.8-folds higher than that of controls (p=0.0045). The present in vivo evidence supports the pathophysiological involvement of oxLDL/β2GPI complexes in atherosclerotic complications of WHHL rabbits. 64Cu-3H3-scFv represents a novel PET imaging probe for non-invasive pathophysiological assessment of oxLDL/β2GPI complexes accumulated in atherosclerotic plaques. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Ticagrelor promotes atherosclerotic plaque stability in a mouse model of advanced atherosclerosis

    Directory of Open Access Journals (Sweden)

    Preusch MR

    2016-08-01

    Full Text Available Michael R Preusch,1 Jonas Rusnak,1 Kathrin Staudacher,2 Carolin Mogler,3 Lorenz Uhlmann,4 Philipp Sievers,1 Florian Bea,1 Hugo A Katus,1 Erwin Blessing,1 Ingo Staudacher1 1Department of Internal Medicine III, 2Department of Neonatology, 3Department of Pathology, 4Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Objective: There is increasing evidence supporting the role of platelets in atherosclerotic vascular disease. The G-protein-coupled receptor P2Y12 is a central mediator of platelet activation and aggregation but has also been linked to platelet-independent vascular disease. Ticagrelor is an oral P2Y12 antagonist that is used as a standard treatment in patients after acute myocardial infarction. However, the effects of ticagrelor on advanced atherosclerosis have not been investigated.Materials and methods: Twenty-week-old apolipoprotein-E-deficient mice received standard chow or standard chow supplemented with 0.15% ticagrelor (approximately 270 mg/kg/day for 25 weeks. The lesion area was evaluated in the aortic sinus by Movat’s pentachrome staining and lesion composition, thickness of the fibrous cap, and size of the necrotic core evaluated by morphometry. RAW 264.7 macrophages were serum starved and treated with ticagrelor in vitro for the detection and quantification of apoptosis. In addition, oxLDL uptake in RAW 264.7 macrophages was evaluated.Results: A trend toward the reduction of total lesion size was detected. However, data did not reach the levels of significance (control, n=11, 565,881 µm2 [interquartile range {IQR} 454,778–603,925 µm2] versus ticagrelor, n=13, 462,595 µm2 [IQR 379,740–546,037 µm2]; P=0.1. A significant reduction in the relative area of the necrotic core (control, n=11, 0.46 [IQR 0.4–0.51] versus ticagrelor, n=13, 0.34 [IQR 0.31–0.39]; P=0.008, and a significant increase in fibrous caps thickness (control, n=11, 3.7 µm [IQR 3.4–4.2 µm] versus

  11. The role of damage- and pathogen-associated molecular patterns in inflammation-mediated vulnerability of atherosclerotic plaques.

    Science.gov (United States)

    Rai, Vikrant; Agrawal, Devendra K

    2017-10-01

    Atherosclerosis is a chronic inflammatory disease resulting in the formation of the atherosclerotic plaque. Plaque formation starts with the inflammation in fatty streaks and progresses through atheroma, atheromatous plaque, and fibroatheroma leading to development of stable plaque. Hypercholesterolemia, dyslipidemia, and hyperglycemia are the risk factors for atherosclerosis. Inflammation, infection with viruses and bacteria, and dysregulation in the endothelial and vascular smooth muscle cells leads to advanced plaque formation. Death of the cells in the intima due to inflammation results in secretion of damage-associated molecular patterns (DAMPs) such as high mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), alarmins (S100A8, S100A9, S100A12, and oxidized low-density lipoproteins), and infection with pathogens leads to secretion of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides, lipoteichoic acids, and peptidoglycans. DAMPs and PAMPs further activate the inflammatory surface receptors such as TREM-1 and toll-like receptors and downstream signaling kinases and transcription factors leading to increased secretion of pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-1β, IL-6, and interferon-γ and matrix metalloproteinases (MMPs). These mediators and cytokines along with MMPs render the plaque vulnerable for rupture leading to ischemic events. In this review, we have discussed the role of DAMPs and PAMPs in association with inflammation-mediated plaque vulnerability.

  12. Dietary Silicon Deficiency Does Not Exacerbate Diet-Induced Fatty Lesions in Female ApoE Knockout Mice.

    Science.gov (United States)

    Jugdaohsingh, Ravin; Kessler, Katharina; Messner, Barbara; Stoiber, Martin; Pedro, Liliana D; Schima, Heinrich; Laufer, Günther; Powell, Jonathan J; Bernhard, David

    2015-07-01

    Dietary silicon has been positively linked with vascular health and protection against atherosclerotic plaque formation, but the mechanism of action is unclear. We investigated the effect of dietary silicon on 1) serum and aorta silicon concentrations, 2) the development of aortic lesions and serum lipid concentrations, and 3) the structural and biomechanic properties of the aorta. Two studies, of the same design, were conducted to address the above objectives. Female mice, lacking the apolipoprotein E (apoE) gene, and therefore susceptible to atherosclerosis, were separated into 3 groups of 10-15 mice, each exposed to a high-fat diet (21% wt milk fat and 1.5% wt cholesterol) but with differing concentrations of dietary silicon, namely: silicon-deprived (-Si; silicon/g feed), silicon-replete in feed (+Si-feed; 100-μg silicon/g feed), and silicon-replete in drinking water (+Si-water; 115-μg silicon/mL) for 15-19 wk. Silicon supplementation was in the form of sodium metasilicate (feed) or monomethylsilanetriol (drinking water). The serum silicon concentration in the -Si group was significantly lower than in the +Si-feed (by up to 78%; P silicon concentration was also lower in the -Si group than in the +Si-feed group (by 65%; P = 0.025), but not compared with the +Si-water group. There were no differences in serum and aorta silicon concentrations between the silicon-replete groups. Body weights, tissue wet weights at necropsy, and structural, biomechanic, and morphologic properties of the aorta were not affected by dietary silicon; nor were the development of fatty lesions and serum lipid concentrations. These findings suggest that dietary silicon has no effect on atherosclerosis development and vascular health in the apoE mouse model of diet-induced atherosclerosis, contrary to the reported findings in the cholesterol-fed rabbit model.

  13. Stiffness Properties of Adventitia, Media, and Full Thickness Human Atherosclerotic Carotid Arteries in the Axial and Circumferential Directions.

    Science.gov (United States)

    Hoffman, Allen H; Teng, Zhongzhao; Zheng, Jie; Wu, Zheyang; Woodard, Pamela K; Billiar, Kristen L; Wang, Liang; Tang, Dalin

    2017-12-01

    Arteries can be considered as layered composite material. Experimental data on the stiffness of human atherosclerotic carotid arteries and their media and adventitia layers are very limited. This study used uniaxial tests to determine the stiffness (tangent modulus) of human carotid artery sections containing American Heart Association type II and III lesions. Axial and circumferential oriented adventitia, media, and full thickness specimens were prepared from six human carotid arteries (total tissue strips: 71). Each artery yielded 12 specimens with two specimens in each of the following six categories; axial full thickness, axial adventitia (AA), axial media (AM), circumferential full thickness, circumferential adventitia (CA), and circumferential media (CM). Uniaxial testing was performed using Inspec 2200 controlled by software developed using labview. The mean stiffness of the adventitia was 3570 ± 667 and 2960 ± 331 kPa in the axial and circumferential directions, respectively, while the corresponding values for the media were 1070 ± 186 and 1800 ± 384 kPa. The adventitia was significantly stiffer than the media in both the axial (p = 0.003) and circumferential (p = 0.010) directions. The stiffness of the full thickness specimens was nearly identical in the axial (1540 ± 186) and circumferential (1530 ± 389 kPa) directions. The differences in axial and circumferential stiffness of media and adventitia were not statistically significant.

  14. Joint learning of ultrasonic backscattering statistical physics and signal confidence primal for characterizing atherosclerotic plaques using intravascular ultrasound.

    Science.gov (United States)

    Sheet, Debdoot; Karamalis, Athanasios; Eslami, Abouzar; Noël, Peter; Chatterjee, Jyotirmoy; Ray, Ajoy K; Laine, Andrew F; Carlier, Stephane G; Navab, Nassir; Katouzian, Amin

    2014-01-01

    Intravascular Ultrasound (IVUS) is a predominant imaging modality in interventional cardiology. It provides real-time cross-sectional images of arteries and assists clinicians to infer about atherosclerotic plaques composition. These plaques are heterogeneous in nature and constitute fibrous tissue, lipid deposits and calcifications. Each of these tissues backscatter ultrasonic pulses and are associated with a characteristic intensity in B-mode IVUS image. However, clinicians are challenged when colocated heterogeneous tissue backscatter mixed signals appearing as non-unique intensity patterns in B-mode IVUS image. Tissue characterization algorithms have been developed to assist clinicians to identify such heterogeneous tissues and assess plaque vulnerability. In this paper, we propose a novel technique coined as Stochastic Driven Histology (SDH) that is able to provide information about co-located heterogeneous tissues. It employs learning of tissue specific ultrasonic backscattering statistical physics and signal confidence primal from labeled data for predicting heterogeneous tissue composition in plaques. We employ a random forest for the purpose of learning such a primal using sparsely labeled and noisy samples. In clinical deployment, the posterior prediction of different lesions constituting the plaque is estimated. Folded cross-validation experiments have been performed with 53 plaques indicating high concurrence with traditional tissue histology. On the wider horizon, this framework enables learning of tissue-energy interaction statistical physics and can be leveraged for promising clinical applications requiring tissue characterization beyond the application demonstrated in this paper. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Delayed 18F-fluorodeoxyglucose PET/CT imaging improves quantitation of atherosclerotic plaque inflammation

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Thomassen, Anders; Takx, Richard A P

    2014-01-01

    BACKGROUND: This study aimed to determine if delayed (18)F-fluorodeoxyglucose ((18)FDG) PET/CT imaging improves quantitation of atherosclerotic plaque inflammation. Blood-pool activity can disturb the arterial (18)FDG signal. With time, blood-pool activity declines. Therefore, delayed imaging can...... at 180 minutes significant positive relations were observed between SCORE % and carotid (τ = 0.25, P = .045) and aortic (τ = 0.33, P = .008) cSUVMAX. CONCLUSIONS: Delayed (18)FDG PET/CT imaging at 180 minutes improves quantitation of atherosclerotic plaque inflammation over imaging at 90 minutes....... Therefore, the optimal acquisition time-point to assess atherosclerotic plaque inflammation lies beyond the advocated time-point of 90 minutes after (18)FDG administration....

  16. Texture based segmentation method to detect atherosclerotic plaque from optical tomography images

    Science.gov (United States)

    Prakash, Ammu; Hewko, Mark; Sowa, Michael; Sherif, Sherif

    2013-06-01

    Optical coherence tomography (OCT) imaging has been widely employed in assessing cardiovascular disease. Atherosclerosis is one of the major cause cardio vascular diseases. However visual detection of atherosclerotic plaque from OCT images is often limited and further complicated by high frame rates. We developed a texture based segmentation method to automatically detect plaque and non plaque regions from OCT images. To verify our results we compared them to photographs of the vascular tissue with atherosclerotic plaque that we used to generate the OCT images. Our results show a close match with photographs of vascular tissue with atherosclerotic plaque. Our texture based segmentation method for plaque detection could be potentially used in clinical cardiovascular OCT imaging for plaque detection.

  17. Assessment of atherosclerotic plaque inflammation can be improved by delayed time point FDG PET CT imaging

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

    2013-01-01

    Objectives: Blood pool FDG activity can cloud the atherosclerotic plaque FDG signal. Over time, blood pool FDG activity declines. Therefore, delayed time point FDG PET CT imaging can potentially enhance the assessment of atherosclerotic plaque inflammation. Methods: Twelve healthy volunteers...... without traditional cardiovascular risk factors and three subjects with angina pectoris were prospectively assessed by dual time point 18-FDG PET CT imaging at 90 and 180 minutes after tracer injection. The ratio between aortic SUVmax and the blood pool SUVmean (TBR) was calculated to show the change......,35; df = 12; P = 0.037). Conclusions: Based on these preliminary data, we can make three conclusions: 1) aging and male gender are significantly correlated to atherosclerotic plaque FDG avidity, 2) over time, a significant increase is observed in TBR, and 3) the increase in cSUV over time results...

  18. Human activin-A is expressed in the atherosclerotic lesion and promotes the contractile phenotype of smooth muscle cells

    NARCIS (Netherlands)

    M.A. Engelse (Marten); J.M. Neele; T.A.E. van Achterberg (Tanja); B.E. van Aken (Benien); R.H.N. van Schaik (Ron); H. Pannekoek (Hans); C.J.M. de Vries (Carlie)

    1999-01-01

    textabstractActivin is a member of the transforming growth factor-beta superfamily, and it modulates the proliferation and differentiation of various target cells. In this study, we investigated the role of activin in the initiation and progression of human atherosclerosis. The

  19. Proliferation and extracellular matrix synthesis of smooth muscle cells cultured from human coronary atherosclerotic and restenotic lesions

    NARCIS (Netherlands)

    D.C. MacLeod (Donald); B.H. Strauss (Bradley); J. Escaned (Javier); V.A.W.M. Umans (Victor); R-J. van Suylen (Robert-Jan); A. Verkerk (Anton); P.J. de Feyter (Pim); P.W.J.C. Serruys (Patrick); M. de Jong (Marcel)

    1994-01-01

    textabstractOBJECTIVES. The purpose of this study was to examine the proliferative capacity and extracellular matrix synthesis of human coronary plaque cells in vitro. BACKGROUND. Common to both primary atherosclerosis and restenosis are vascular smooth muscle cell proliferation and production of

  20. Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions

    NARCIS (Netherlands)

    de Boer, Onno J.; van der Meer, Jelger J.; Teeling, Peter; van der Loos, Chris M.; van der Wal, Allard C.

    2007-01-01

    BACKGROUND: T cell mediated inflammation contributes to atherogenesis and the onset of acute cardiovascular disease. Effector T cell functions are under a tight control of a specialized T cell subset, regulatory T cells (Treg). At present, nothing is known about the in situ presence of Treg in human

  1. Plasma viscosity increase with progression of peripheral arterial atherosclerotic disease.

    Science.gov (United States)

    Poredos, P; Zizek, B

    1996-03-01

    -macroglobulin (r=0.78, P < 0.01). These results indicate that in patients with peripheral arterial disease plasma viscosity increases with the progression of the atherosclerotic process and is correlated with the clinical stages of the disease.

  2. Lipid lowering and anti-atherosclerotic properties of Tinospora ...

    African Journals Online (AJOL)

    No foam cell formation was visible in aorta of rabbits treated with TCAE in dose dependent manner. However, there was visible foam cell formation in the aorta of hyperlipidemia group. In conclusion, this study suggests that supplementation of 450 mg/kg of T. crispa extract would be able to reduce or retard the progression ...

  3. Bacteria and bacterial DNA in atherosclerotic plaque and aneurysmal wall biopsies from patients with and without periodontitis

    Directory of Open Access Journals (Sweden)

    Zahra Armingohar

    2014-05-01

    Full Text Available Background: Several studies have reported an association between chronic periodontitis (CP and cardiovascular diseases. Detection of periodontopathogens, including red complex bacteria (RCB, in vascular lesions has suggested these bacteria to be involved in the pathogenesis of atherosclerosis and abdominal aortic aneurysms. Objective: In this study, we investigate bacteria and their DNA in vascular biopsies from patients with vascular diseases (VD; i.e. abdominal aortic aneurysms, atherosclerotic carotid, and common femoral arteries, with and without CP. Methods: DNA was extracted from vascular biopsies selected from 40 VD patients: 30 with CP and 10 without CP. The V3-V5 region of the 16S rDNA (V3-V5 was polymerase chain reaction (PCR-amplified, and the amplicons were cloned into Escherichia coli, sequenced, and classified (GenBank and the Human Oral Microbiome database. Species-specific primers were used for the detection of Porphyromonas gingivalis. In addition, 10 randomly selected vascular biopsies from the CP group were subjected to scanning electron microscopy (SEM for visualization of bacteria. Checkerboard DNA–DNA hybridization was performed to assess the presence of RCB in 10 randomly selected subgingival plaque samples from CP patients. Results: A higher load and mean diversity of bacteria were detected in vascular biopsies from VD patients with CP compared to those without CP. Enterobacteriaceae were frequently detected in vascular biopsies together with cultivable, commensal oral, and not-yet-cultured bacterial species. While 70% of the subgingival plaque samples from CP patients showed presence of RCB, only P. gingivalis was detected in one vascular biopsy. Bacterial cells were seen in all 10 vascular biopsies examined by SEM. Conclusions: A higher bacterial load and more diverse colonization were detected in VD lesions of CP patients as compared to patients without CP. This indicated that a multitude of bacterial species both

  4. Molecular analysis of oral bacteria in dental biofilm and atherosclerotic plaques of patients with vascular disease.

    Science.gov (United States)

    Fernandes, Clarissa Pessoa; Oliveira, Francisco Artur Forte; Silva, Paulo Goberlânio de Barros; Alves, Ana Paula Negreiros Nunes; Mota, Mário Rogério Lima; Montenegro, Raquel Carvalho; Burbano, Rommel Mario Rodriguez; Seabra, Aline Damasceno; Lobo Filho, José Glauco; Lima, Danilo Lopes Ferreira; Soares Filho, Antônio Wilon Evelin; Sousa, Fabrício Bitu

    2014-07-01

    Oral bacteria have been detected in atherosclerotic plaques at a variable frequency; however, the connection between oral health and vascular and oral bacterial profiles of patients with vascular disease is not clearly established. The aim of this study was to evaluate the presence of oral bacterial DNA in the mouth and atherosclerotic plaques, in addition to assessing the patients' caries and periodontal disease history. Thirty samples of supragingival and subgingival plaque, saliva and atherosclerotic plaques of 13 patients with carotid stenosis or aortic aneurysm were evaluated, through real-time polymerase chain reaction, for the presence of Streptococcus mutans (SM), Prevotella intermedia (PI), Porphyromonas gingivalis (PG) and Treponema denticola (TD). All patients were submitted to oral examination using the DMFT (decayed, missing and filled teeth) and PSR (Periodontal Screening and Recording) indexes. Histopathological analysis of the atherosclerotic plaques was performed. Most of the patients were edentulous (76.9%). SM, PI, PG and TD were detected in 100.0%, 92.0%, 15.3% and 30.7% of the oral samples, respectively. SM was the most prevalent targeted bacteria in atherosclerotic plaques, detected in 100% of the samples, followed by PI (7.1%). The vascular samples were negative for PG and TD. There was a statistically significant difference (p<0.05) between the presence of PG and TD in the oral cavity and vascular samples. SM was found at a high frequency in oral and vascular samples, even in edentulous patients, and its presence in atherosclerotic plaques suggests the possible involvement of this bacterium in the disease progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. {sup 68}Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    Energy Technology Data Exchange (ETDEWEB)

    Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Iveson, Peter; Wilson, Ian [Medical Diagnostics, GE Healthcare Biosciences, London (United Kingdom); Karlsen, Hege; Cuthbertson, Alan [GE Healthcare MDx Research, Oslo (Norway); Laine, Jukka [Turku University Hospital, Department of Pathology, Turku (Finland); Leppaenen, Pia; Ylae-Herttula, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland); Roivainen, Anne [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Turku Centre for Disease Modelling, Turku (Finland)

    2009-12-15

    Increased expression of {alpha}v{beta}3/{alpha}v{beta}5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel {sup 68}Ga-DOTA-RGD peptide binds with high affinity to {alpha}v{beta}3/{alpha}v{beta}5 integrin. The aim of this study was to investigate the uptake of the {sup 68}Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered {sup 68}Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR{sup -/-}ApoB{sup 100/100} atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced {sup 68}Ga. The tracer had reasonably good specific radioactivity (8.7 {+-} 1.1 GBq/{mu}mol) and was quite stable in vivo. According to ex vivo biodistribution results, {sup 68}Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of {sup 68}Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio {+-} SD 1.4 {+-} 0.1, p = 0.0004). We observed that {sup 68}Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

  6. Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations

    NARCIS (Netherlands)

    Vegter, Eline L.; Ovchinnikova, Ekaterina S.; van Veldhuisen, Dirk J.; Jaarsma, Tiny; Berezikov, Eugene; van der Meer, Peter; Voors, Adriaan A.

    Objective Circulating microRNAs (miRNAs) have been implicated in both heart failure and atherosclerotic disease. The aim of this study was to examine associations between heart failure specific circulating miRNAs, atherosclerotic disease and cardiovascular-related outcome in patients with heart

  7. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism

    DEFF Research Database (Denmark)

    Helgadottir, Anna; Gretarsdottir, Solveig; Thorleifsson, Gudmar

    2012-01-01

    The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components.......The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components....

  8. Renovascular heart failure: heart failure in patients with atherosclerotic renal artery disease.

    Science.gov (United States)

    Kawarada, Osami; Yasuda, Satoshi; Noguchi, Teruo; Anzai, Toshihisa; Ogawa, Hisao

    2016-07-01

    Atherosclerotic renal artery disease presents with a broad spectrum of clinical features, including heart failure as well as hypertension, and renal failure. Although recent randomized controlled trials failed to demonstrate renal artery stenting can reduce blood pressure or the number of cardiovascular or renal events more so than medical therapy, increasing attention has been paid to flash pulmonary edema and congestive heart failure associated with atherosclerotic renal artery disease. This clinical entity "renovascular heart failure" is diagnosed retrospectively. Given the increasing global burden of heart failure, this review highlights the background and catheter-based therapeutic aspects for renovascular heart failure.

  9. Ultrastructural researches on rabbit myxomatosis. Lymphnodal lesions.

    Science.gov (United States)

    Marcato, P S; Simoni, P

    1977-07-01

    Ultrastructural examination of head and neck lymph nodes in rabbits with spontaneous subacute myxomatosis showed fusion of immature reticuloendothelial cells which lead to the formation of polykarocytes. There was no ultrastructural evidence of viral infection of these polykaryocytes. Histiosyncytial lymphadenitis can be considered a specific lesion of myxomatosis.

  10. Intraosseous osteolytic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Adler, C.P.; Wenz, W.

    1981-10-01

    Any pathological damage occurring in a bone will produce either an osteolytic or osteosclerotic lesion which can be seen in the macroscopic specimen as well as in the roentgenogram. Various bone lesions may lead to local destructions of the bone. An osteoma or osteoplastic osteosarcoma produces an osteosclerotic lesion showing a dense mass in the roentgenogram; a chondroblastoma or an osteoclastoma, on the other hand, induces an osteolytic focal lesion. This paper presents examples of different osteolytic lesions of the humerus. An osteolytic lesion seen in the roentgenogram may be either produced by an underlying non-ossifying fibroma of the bone, by fibrous dysplasia, osteomyelitis or Ewing's sarcoma. Differential diagnostic considerations based on the radiological picture include eosinophilic bone granuloma, juvenile or aneurysmal bone cyst, multiple myeloma or bone metastases. Serious differential diagnostic problems may be involved in case of osteolytic lesions occurring in the humerus. Cases of this type involving complications have been reported and include the presence of an teleangiectatic osteosarcoma as well as that of a hemangiosarcoma of the bone.

  11. Estimating risk of atherosclerotic cardiovascular diseases in non-atherosclerotic Pakistani patients: Study conducted at National Institute of Cardiovascular Diseases, Karachi, Pakistan.

    Science.gov (United States)

    Ashraf, Tariq; Achakzai, Abdul Samad; Farooq, Fawad; Memon, Muhammad Anis; Mengal, Naeem; Abbas, Khawaja Yawar; Ishaq, Haroon; Mueed, Abdul

    2017-04-01

    To assess ten-year and lifetime estimated cardiovascular disease risks in non-atherosclerotic subjects. This cross-sectional study was carried out at the National Institute of Cardiovascular Disease, Karachi, from July 2014 to March 2015, and comprised male and female subjects with multi-ethnic background, aged 20-79 years and having non-atherosclerotic disease. SPSS 22 was used for data analysis. Of the 437 participants, 174(39.8%) were men and 263(60.2%) were women. The overall mean age was 42.65±11.45 years. The mean age of men was 43.3±12.1 years and that of women was 42.2±10.8 years. Moreover, ten-year and lifetime risk assessment rates were higher in men (50[28.2%] and 86[49.4%] respectively) compared to women (28[10.6%] and 84[31.9%], respectively). Urdu-speaking Pakistanis were found to be at higher risk from atherosclerotic cardiovascular disease.

  12. Image-based numerical modeling of HIFU-induced lesions

    Science.gov (United States)

    Almekkaway, Mohamed K.; Shehata, Islam A.; Haritonova, Alyona; Ballard, John; Casper, Andrew; Ebbini, Emad

    2017-03-01

    Atherosclerosis is a chronic vascular disease affecting large and medium sized arteries. Several treatment options are already available for treatment of this disease. Targeting atherosclerotic plaques by high intensity focused ultrasound (HIFU) using dual mode ultrasound arrays (DMUA) was recently introduced in literature. We present a finite difference time domain (FDTD) simulation modeling of the wave propagation in heterogeneous medium from the surface of a 3.5 MHz array prototype with 32-elements. After segmentation of the ultrasound image obtained for the treatment region in-vivo, we integrated this anatomical information into our simulation to account for different parameters that may be caused by these multi-region anatomical complexities. The simulation program showed that HIFU was able to induce damage in the prefocal region instead of the target area. The HIFU lesions, as predicted by our simulation, were well correlated with the actual damage detected in histology.

  13. Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

    Energy Technology Data Exchange (ETDEWEB)

    Karki, Rajendra [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City (United States); Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of); Kim, Seong-Bin [Jeollanamdo Development Institute for Korean Traditional Medicine, Jangheung gun, Jeollanamdo (Korea, Republic of); Kim, Dong-Wook, E-mail: dbkim@mokpo.ac.kr [Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of)

    2013-12-10

    Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

  14. Effect of light intensity on Sekiguchi lesion development in lesion mimic mutant of rice inoculated with Magnaporthe grisea

    OpenAIRE

    Ueno, Makoto; Imaoka, Atsuko; Kihara, Junichi; Arase, Sakae

    2006-01-01

    The effect of light intensity on Sekiguchi lesion formation and tryptamine accumulation involved in light-induced resistance of rice(cv. Sekiguchi-asahi)inoculated with Magnaporthe grisea was determined by using neutral density filters(ND). When the M. griseainoculated leaves were irradiated by ND-filtered lights from daylight fluorescent lamps, there was no difference in number of Sekiguchi lesions among attenuation rates0,20,50,75and90%. However Sekiguchi lesion development and tryptamine a...

  15. Gram stain of skin lesion

    Science.gov (United States)

    Skin lesion gram stain ... skin sore. This procedure is called a skin lesion biopsy . Before the biopsy, your provider will numb ... means bacteria have been found in the skin lesion. Further tests are needed to confirm the results. ...

  16. Acute periodontal lesions

    OpenAIRE

    Herrera Gonzalez, David; Alonso Álvarez, Bettina; Arriba de la Fuente, Lorenzo; Santa- Cruz Astorqui, Isabel; Serrano, Cristina; Sanz Alonso, Mariano

    2014-01-01

    This is a review and update on acute conditions affecting the gingival tissues, including abscesses in the periodontium, necrotizing periodontal diseases, and other acute conditions that cause gingival lesions with acute presentation, such as infectious process not associated with oral bacterial biofilms, muco-cutanenous disorders, and traumatic and allergic lesions. A periodontal abscess is clinically important since it is a relatively frequent dental emergency, it can compromise the periodo...

  17. Frequency of USP6 rearrangements in myositis ossificans, brown tumor, and cherubism: molecular cytogenetic evidence that a subset of "myositis ossificans-like lesions" are the early phases in the formation of soft-tissue aneurysmal bone cyst.

    Science.gov (United States)

    Sukov, William R; Franco, Marcello F; Erickson-Johnson, Michele; Chou, Margaret M; Unni, K Krishnan; Wenger, Doris E; Wang, Xiaoke; Oliveira, Andre M

    2008-04-01

    USP6 rearrangements with several partner genes have been identified recently in primary but not in secondary aneurysmal bone cysts (ABCs). Several lesions show histologic features that may overlap with ABC, including myositis ossificans (MO), brown tumor, and cherubism. The objective of this study was to assess whether these lesions harbored USP6 rearrangements. Twelve patients with classic radiologic and histologic features of MO, 6 with brown tumors, and 5 with cherubism diagnosed at our institution were studied for the presence of USP6 rearrangements using fluorescence in situ hybridization with probes flanking the USP6 locus on chromosome 17p13. In addition, conventional cytogenetic analysis was performed in 2 patients with cherubism. USP6 rearrangements were identified in 2 patients with radiologic and histologic features consistent with MO. None of the patients with brown tumor or cherubism demonstrated USP6 rearrangements. Cytogenetic analysis of the cherubism patients demonstrated normal karyotypes. These findings indicate that a subset of cases with apparent classic histologic and imaging features of MO are rather better classified as being soft-tissue ABC with clonal USP6 rearrangements. In contrast, no USP6 rearrangements were found in patients with cherubism or brown tumor, supporting the prevailing view that these lesions are distinct biologic entities.

  18. Traditional lesion detection aids.

    Science.gov (United States)

    Neuhaus, K W; Ellwood, R; Lussi, A; Pitts, N B

    2009-01-01

    Lesion detection aids ideally aim at increasing the sensitivity of visual caries detection without trading off too much in terms of specificity. The use of a dental probe (explorer), bitewing radiography and fibre-optic transillumination (FOTI) have long been recommended for this purpose. Today, probing of suspected lesions in the sense of checking the 'stickiness' is regarded as obsolete, since it achieves no gain of sensitivity and might cause irreversible tooth damage. Bitewing radiography helps to detect lesions that are otherwise hidden from visual examination, and it should therefore be applied to a new patient. The diagnostic performance of radiography at approximal and occlusal sites is different, as this relates to the 3-dimensional anatomy of the tooth at these sites. However, treatment decisions have to take more into account than just lesion extension. Bitewing radiography provides additional information for the decision-making process that mainly relies on the visual and clinical findings. FOTI is a quick and inexpensive method which can enhance visual examination of all tooth surfaces. Both radiography and FOTI can improve the sensitivity of caries detection, but require sufficient training and experience to interpret information correctly. Radiography also carries the burden of the risks and legislation associated with using ionizing radiation in a health setting and should be repeated at intervals guided by the individual patient's caries risk. Lesion detection aids can assist in the longitudinal monitoring of the behaviour of initial lesions. Copyright 2009 S. Karger AG, Basel

  19. Oral lesions in leprosy

    Directory of Open Access Journals (Sweden)

    Costa A

    2003-11-01

    Full Text Available BACKGROUND: Leprotic oral lesions are more common in the lepromatous form of leprosy, indicate a late manifestation, and have a great epidemiological importance as a source of infection. METHODS: Patients with leprosy were examined searching for oral lesions. Biopsies of the left buccal mucosa in all patients, and of oral lesions, were performed and were stained with H&E and Wade. RESULTS: Oral lesions were found in 26 patients, 11 lepromatous leprosy, 14 borderline leprosy, and one tuberculoid leprosy. Clinically 5 patients had enanthem of the anterior pillars, 3 of the uvula and 3 of the palate. Two had palatal infiltration. Viable bacilli were found in two lepromatous patients. Biopsies of the buccal mucosa showed no change or a nonspecific inflammatory infiltrate. Oral clinical alterations were present in 69% of the patients; of these 50% showed histopathological features in an area without any lesion. DISCUSSION: Our clinical and histopathological findings corroborate earlier reports that there is a reduced incidence of oral changes, which is probably due to early treatment. The maintenance of oral infection in this area can also lead to and maintain lepra reactions, while they may also act as possible infection sources. Attention should be given to oral disease in leprosy because detection and treatment of oral lesions can prevent the spread of the disease.

  20. Aspects of haemostatic function in healthy subjects with microalbuminuria--a potential atherosclerotic risk factor

    DEFF Research Database (Denmark)

    Jensen, J S; Myrup, B; Borch-Johnsen, K

    1995-01-01

    Microalbuminuria, i.e., slightly elevated urinary albumin excretion rate (UAER), notifies increased risk for atherosclerotic disease and may reflect an early generalized vascular abnormality in healthy subjects. This study was designed in order to examine whether such abnormality is associated wi...

  1. Angiopoietin-2 blocking antibodies reduce early atherosclerotic plaque development in mice

    NARCIS (Netherlands)

    Theelen, Thomas L.; Lappalainen, Jari P.; Sluimer, Judith C.; Gurzeler, Erika; Cleutjens, Jack P.; Gijbels, Marion J.; Biessen, Erik A. L.; Daemen, Mat J. A. P.; Alitalo, Kari; Ylä-Herttuala, Seppo

    2015-01-01

    Angiopoietin-2 (Ang-2) blocking agents are currently undergoing clinical trials for use in cancer treatment. Ang-2 has also been associated with rupture-prone atherosclerotic plaques in humans, suggesting a role for Ang-2 in plaque stability. Despite the availability of Ang-2 blocking agents, their

  2. Positron emission tomography of the vulnerable atherosclerotic plaque in man – a contemporary review

    DEFF Research Database (Denmark)

    Pedersen, Sune F; Hag, Anne Mette F; Klausen, Thomas L

    2014-01-01

    to treat symptomatic patients with high-grade carotid artery stenosis due to atherosclerosis - a procedure known as carotid endarterectomy (CEA). By removing the atherosclerotic plaque from the affected carotid artery of these patients, CEA is beneficial by preventing subsequent ipsilateral ischemic stroke...

  3. 3D reconstruction of carotid atherosclerotic plaque: comparison between spatial compound ultrasound models and anatomical models

    DEFF Research Database (Denmark)

    Lind, Bo L.; Fagertun, Jens; Wilhjelm, Jens E.

    2007-01-01

    This study deals with the creation of 3D models that can work as a tool for discriminating between tissue and background in the development of tissue classification methods. Ten formalin-fixed atherosclerotic carotid plaques removed by endarterectomy were scanned with 3D multi-angle spatial...

  4. Feasibility of simultaneous PET/MR in diet-induced atherosclerotic minipig

    DEFF Research Database (Denmark)

    Pedersen, Sune F; Ludvigsen, Trine Pagh; Johannesen, Helle H

    2014-01-01

    Novel hybrid 18-fluoro-deoxy-D-glucose ((18)F-FDG) based positron emission tomography (PET) and magnetic resonance imaging (MRI) has shown promise for characterization of atherosclerotic plaques clinically. The purpose of this study was to evaluate the method in a pre-clinical model of diet-induc...

  5. β-Sarcoglycan Deficiency Reduces Atherosclerotic Plaque Development in ApoE-Null Mice.

    Science.gov (United States)

    Murugesan, Vignesh; Degerman, Eva; Holmen-Pålbrink, Ann-Kristin; Duner, Pontus; Knutsson, Anki; Hultgårdh-Nilsson, Anna; Rauch, Uwe

    2017-01-01

    Smooth muscle cells are important for atherosclerotic plaque stability. Their proper ability to communicate with the extracellular matrix is crucial for maintaining the correct tissue integrity. In this study, we have investigated the role of β-sarcoglycan within the matrix-binding dystrophin-glycoprotein complex in the development of atherosclerosis. Atherosclerotic plaque development was significantly reduced in ApoE-deficient mice lacking β-sarcoglycan, and their plaques contained an increase in differentiated smooth muscle cells. ApoE-deficient mice lacking β-sarcoglycan showed a reduction in ovarian adipose tissue and adipocyte size, while the total weight of the animals was not significantly different. Western blot analysis of adipose tissues showed a decreased activation of protein kinase B, while that of AMP-activated kinase was increased in mice lacking β-sarcoglycan. Analysis of plasma in β-sarcoglycan-deficient mice revealed reduced levels of leptin, adiponectin, insulin, cholesterol, and triglycerides but increased levels of IL-6, IL-17, and TNF-α. Our results indicate that the dystrophin-glycoprotein complex and β-sarcoglycan can affect the atherosclerotic process. Furthermore, the results show the effects of β-sarcoglycan deficiency on adipose tissue and lipid metabolism, which may also have contributed to the atherosclerotic plaque reduction. © 2017 S. Karger AG, Basel.

  6. Atherosclerotic risk and social jetlag in rotating shift-workers : First evidence from a pilot study

    NARCIS (Netherlands)

    Kantermann, Thomas; Duboutay, Françoise; Haubruge, Damien; Kerkhofs, Myriam; Schmidt-Trucksäss, Arno; Skene, Debra J

    2013-01-01

    OBJECTIVE: The aim of this study was to identify atherosclerotic risk using pulse wave velocity (PWV) in steel workers employed in different shift-work rotations, and to elucidate its relationship to social jetlag and shift schedule details. PARTICIPANTS: Male workers in a steel factory (n=77, 32

  7. Treatment of periodontitis improves the atherosclerotic profile : a systematic review and meta-analysis

    NARCIS (Netherlands)

    Teeuw, Wijnand J.; Slot, Dagmar E.; Susanto, Hendri; Gerdes, Victor E. A.; Abbas, Frank; D'Aiuto, Francesco; Kastelein, John J. P.; Loos, Bruno G.

    AimSystematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. Material and MethodsLiterature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials,

  8. Treatment of periodontitis improves the atherosclerotic profile: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Teeuw, W.J.; Slot, D.E.; Susanto, H.; Gerdes, V.E.A.; Abbas, F.; D'Aiuto, F.; Kastelein, J.J.P.; Loos, B.G.

    2014-01-01

    Aim Systematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. Material and Methods Literature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials,

  9. Treatment of periodontitis improves the atherosclerotic profile: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Teeuw, Wijnand J.; Slot, Dagmar E.; Susanto, Hendri; Gerdes, Victor E. A.; Abbas, Frank; D'Aiuto, Francesco; Kastelein, John J. P.; Loos, Bruno G.

    2014-01-01

    AimSystematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. Material and MethodsLiterature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials,

  10. A Meta Analysis and Hierarchical Classification of HU-Based Atherosclerotic Plaque Characterization Criteria

    NARCIS (Netherlands)

    Kristanto, Wisnumurti; van Ooijen, Peter M. A.; Jansen-van der Weide, Marijke C.; Vliegenthart, Rozemarijn; Oudkerk, Matthijs

    2013-01-01

    Background: Many computed tomography (CT) studies have reported that lipid-rich, presumably rupture-prone atherosclerotic plaques can be characterized according to their Hounsfield Unit (HU) value. However, the published HU-based characterization criteria vary considerably. The present study aims to

  11. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard

    2012-01-01

    Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and ...

  12. 16S rRNA-based detection of oral pathogens in coronary atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Mahendra Jaideep

    2010-01-01

    Full Text Available Background: Atherosclerosis develops as a response of the vessel wall to injury. Chronic bacterial infections have been associated with an increased risk for atherosclerosis and coronary artery disease. The ability of oral pathogens to colonize in coronary atheromatous plaque is well known. Aim: The aim of this study was to detect the presence of Treponema denticola, Porphyromonas gingivalis and Campylobacter rectus in the subgingival and atherosclerotic plaques of patients with coronary artery disease. Materials and Methods: Fifty-one patients in the age group of 40-80 years with coronary artery disease were selected for the study. DNA was extracted from the plaque samples. The specific primers for T. denticola, C. rectus and P. gingivalis were used to amplify a part of the 16S rRNA gene by polymerase chain reaction. Statistical Analysis Used: Chi-square analysis, correlation coefficient and prevalence percentage of the microorganisms were carried out for the analysis. Results: Of the 51 patients, T. denticola, C. rectus and P. gingivalis were detected in 49.01%, 21.51% and 45.10% of the atherosclerotic plaque samples. Conclusions: Our study revealed the presence of bacterial DNA of the oral pathogenic microorganisms in coronary atherosclerotic plaques. The presence of the bacterial DNA in the coronary atherosclerotic plaques in significant proportion may suggest the possible relationship between periodontal bacterial infection and genesis of coronary atherosclerosis.

  13. The association between atherosclerotic risk factors and renal function in the general population

    NARCIS (Netherlands)

    Verhave, JC; Hillege, HL; Burgerhof, JGM; Gansevoort, RT; de Zeeuw, D; de Jong, PE

    Background. Generalized atherosclerosis is increasingly recognized as an important cause of end-stage renal disease (ESRD). We questioned to what extent atherosclerotic risk factors determine renal function in the general population. Methods. We used baseline data of the Prevention of Renal and

  14. In vivo transfer of lipoprotein(a) into human atherosclerotic carotid arterial intima

    DEFF Research Database (Denmark)

    Nielsen, Lars Bo; Grønholdt, Marie-Louise; Schroeder, T V

    1997-01-01

    The aim of this study was to compare the atherogenic potential of lipoprotein(a) [Lp(a)] and LDL by measuring the intimal clearance of these two plasma lipoproteins in the atherosclerotic intima of the human carotid artery in vivo. Autologous 131I-Lp(a) and 125I-LDL were mixed and reinjected intr...

  15. Repair of an Atherosclerotic Coronary Artery Aneurysm by Implantation of a Coronary Covered Stent

    Directory of Open Access Journals (Sweden)

    Antenor Portela

    2002-05-01

    Full Text Available An atherosclerotic aneurysm of the right coronary artery complicated by a recent myocardial infarction was successfully treated with coronary artery stenting, using a device consisting of 2 stents with a layer of expandable polytetrafluorethylene (PTFE placed between them. A follow-up angiograph 5 months after the procedure showed sustained initial results.

  16. Repair of an Atherosclerotic Coronary Artery Aneurysm by Implantation of a Coronary Covered Stent

    OpenAIRE

    Portela, Antenor; Bastos, Raldir; Costa, Itamar; Paiva, Jayro

    2002-01-01

    An atherosclerotic aneurysm of the right coronary artery complicated by a recent myocardial infarction was successfully treated with coronary artery stenting, using a device consisting of 2 stents with a layer of expandable polytetrafluorethylene (PTFE) placed between them. A follow-up angiograph 5 months after the procedure showed sustained initial results.

  17. Cognitive functioning and quality of life of atherosclerotic patients following carotid endarterectomy.

    NARCIS (Netherlands)

    Bossema, E.R.; Brand, A.N.; Moll, F.L.; Ackerstaff, R.G.A.; Doornen, L.J.P. van

    2002-01-01

    Background: Carotid endarterectomy (CEA) is a surgical procedure to remove atherosclerotic plaque from one of the carotid arteries in patients with severe stenosis. The purpose is to prevent future cerebral ischemic attacks. Whether patients, in addition, improve in cognitive functions and quality

  18. Effect of rosuvastatin on inflammatory factors and carotid atherosclerotic plaque in patients with acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    YAN Jun

    2013-10-01

    Full Text Available Carotid atherosclerosis is closely related with ischemic stroke occurrence, development and recurrence. This study aims to make an evaluation of the effects of rosuvastatin on inflammatory factors, serum lipid and carotid atherosclerotic plaque in patients with acute ischemic stroke. In this study, 98 patients with acute ischemic stroke and carotid atherosclerosis were given oral administration of rosuvastatin calcium (10 mg once every night, and the course of treatment was 6 months. After treatment, the changes of serum high-sensitivity C-reactive protein (hs-CRP, tumor necrosis factor-alpha (TNF-α and blood lipid were measured, as well as carotid atherosclerotic intima-media thickness (IMT and the calculation of carotid atherosclerotic plaque score. According to the examination results, after 6 months' treatment with rosuvastatin, serum hs-CRP, TNF-α, total cholesterol (TC, triglyceride (TG and low-density lipoprotein cholestrol (LDL-C decreased significantly (P < 0.01, for all, while high-density lipoprotein cholestrol (HDL-C increased significantly (P < 0.01; the total number of plaque reduced, while the number of stable plaque increased (P < 0.05; carotid artery IMT and carotid artery plaque score decreased significantly (P < 0.05. There were significant differences between before and after treatment. The results of this study show that rosuvastatin plays a role in anti-inflammation and alleviates the degree of carotid atherosclerotic plaque.

  19. Fast and Accurate Pressure-Drop Prediction in Straightened Atherosclerotic Coronary Arteries

    NARCIS (Netherlands)

    J.T.C. Schrauwen (Jelle); D. Koeze (Dion); J.J. Wentzel (Jolanda); F.N. van de Vosse (Frans); A.F.W. van der Steen (Ton); F.J.H. Gijsen (Frank)

    2014-01-01

    textabstractAtherosclerotic disease progression in coronary arteries is influenced by wall shear stress. To compute patient-specific wall shear stress, computational fluid dynamics (CFD) is required. In this study we propose a method for computing the pressure-drop in regions proximal and distal to

  20. Disease-specific molecular events in cortical multiple sclerosis lesions

    National Research Council Canada - National Science Library

    Fischer, Marie Therese; Wimmer, Isabella; Höftberger, Romana; Gerlach, Susanna; Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Mahad, Don; Binder, Christoph J; Krumbholz, Markus; Bauer, Jan; Bradl, Monika; Lassmann, Hans

    2013-01-01

    Cortical lesions constitute an important part of multiple sclerosis pathology. Although inflammation appears to play a role in their formation, the mechanisms leading to demyelination and neurodegeneration are poorly understood...

  1. Preventive and therapeutic moderate aerobic exercise programs convert atherosclerotic plaques into a more stable phenotype.

    Science.gov (United States)

    Cardinot, Themis M; Lima, Thais M; Moretti, Ana I S; Koike, Marcia K; Nunes, Valeria S; Cazita, Patricia M; Krieger, Marta H; Brum, Patricia C; Souza, Heraldo P

    2016-05-15

    The mechanisms by which exercise affects atherosclerotic plaque stability remain incompletely understood. We evaluated the effects of two training protocols on both atherosclerotic plaque structure and the signaling pathways involved in plaque rupture. Male low-density lipoprotein (LDL) receptor knockout mice were fed a high-fat, high-cholesterol diet (HFD). One group was subjected to moderate exercise using a treadmill for 14weeks (preventive protocol). The other group started an exercise regimen after 16weeks of the HFD (therapeutic group). Atherosclerotic plaques within the aorta were evaluated for lipid and collagen contents, as well as for inflammatory markers. Plasma cholesterol and cytokine levels were also determined. The mice receiving a HFD developed hypercholesterolemia and atherosclerotic plaques within the aorta. The aortas from the animals in the preventive protocol exhibited smaller lipid cores and higher collagen content. These animals also exhibited lower CD40 expression within the plaques. The aortas of the mice in the therapeutic group exhibited higher collagen content, but no differences in either lipid core size or plaque size were noted. No differences in blood pressure, plasma cholesterol, cytokine levels, plaque size or metalloproteinase 9 expression were observed in the trained animals compared with the sedentary animals. Moderate aerobic exercise modified atherosclerotic plaque characteristics and converted the plaques into a more stable phenotype, increasing the collagen content in response to both exercise programs. Furthermore, moderate aerobic exercise reduced the animals' fat content and decreased the activity of the CD40-CD40L signaling pathway in the preventive group. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Antihypercholesterolemic and antioxidant efficacies of zerumbone on the formation, development, and establishment of atherosclerosis in cholesterol-fed rabbits

    Science.gov (United States)

    Hemn, Hassan Othman; Noordin, Muhammad Mustapha; Rahman, Heshu Sulaiman; Hazilawati, Hamza; Zuki, Abubakr; Chartrand, Max Stanley

    2015-01-01

    Owing to the high incidence of cholesterol-induced cardiovascular disease, particularly atherosclerosis, the current study was designed to investigate the preventive and therapeutic efficacies of dietary zerumbone (ZER) supplementation on the formation and development of atherosclerosis in rabbits fed with a high cholesterol diet. A total of 72 New Zealand white rabbits were divided randomly on two experimental studies carried out 8 weeks apart. The first experiment was designed to investigate the prophylactic efficacy of ZER in preventing early developed atheromatous lesion. The second experimental trial was aimed at investigating the therapeutic effect of ZER in reducing the atherosclerotic lesion progression and establishment. Sudanophilia, histopathological, and ultrastructural changes showed pronounced reduction in the plaque size in ZER-medicated aortas. On the other hand, dietary supplementation of ZER for almost 10 weeks as a prophylactic measure indicated substantially decreasing lipid profile values, and similarly, plaque size in comparison with high-cholesterol non-supplemented rabbits. Furthermore, the results of oxidative stress and antioxidant biomarker evaluation indicated that ZER is a potent antioxidant in suppressing the generation of free radicals in terms of atherosclerosis prevention and treatment. ZER significantly reduced the value of malondialdehyde and augmented the value of superoxide dismutase. In conclusion, our data indicated that dietary supplementation of ZER at doses of 8, 16, and 20 mg/kg alone as a prophylactic measure, and as a supplementary treatment with simvastatin, significantly reduced early plague formation, development, and establishment via significant reduction in serum lipid profile, together with suppression of oxidative damage, and therefore alleviated atherosclerosis lesions. PMID:26347047

  3. Using microgravity for defining novel anti-atherosclerotic therapy

    NARCIS (Netherlands)

    Verhaar, A; Krishnadath, KK; Peppelenbosch, MP

    2005-01-01

    Among the most important insights into coronary and inflammatory disease is that the formation of vessel occluding placques is its essence an inflammatory process, that is counteracted by anti-inflammatory drugs Current therapeutical options of dealing with the increased challenge to public health

  4. Coronary artery plaque formation at coronary CT angiography: morphological analysis and relationship to hemodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Enrico, Benedetta [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Universita' Cattolica del Sacro Cuore, Department of Radiology, Rome (Italy); Suranyi, Pal; Costello, Philip [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Thilo, Christian; Schoepf, U.J. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Division of Cardiology, Department of Medicine, Charleston, SC (United States); Bonomo, Lorenzo [Universita' Cattolica del Sacro Cuore, Department of Radiology, Rome (Italy)

    2009-04-15

    We aimed to demonstrate that coronary CT angiography (cCTA) can be used to non-invasively study the effect of hemodynamic factors in the pathophysiology of plaque formation. cCTA data of 73 patients were analyzed. All detected plaques were classified according to location (bifurcation, non-branching segment), configuration (eccentric, concentric), orientation (myocardial, lateral, epicardial side of the vessel wall), and composition (calcified, mixed, non-calcified). Bifurcation lesions were further characterized using the Medina classification. Of 382 plaques, 8.1% were in the LM, 46.3% in the LAD, 18.3% in the LCx, and 25.9% in the RCA. Also, 25.1% were completely calcified, 72.3% were mixed, and 2.6% were purely non-calcified. Of the plaques, 51.3% were bifurcation lesions. The most frequent (40%) Medina pattern was 1.1.0 (lesion starts before, extends beyond bifurcation, sparing the side branch). Eighty percent of plaques were eccentric. A significant (p < 0.01) majority (55%) were on the myocardial side, while 17.3% were lateral, and 27.7% epicardial. Of all non-calcified and mixed plaques, 45.1% (p < 0.01) were myocardial, whereas only 14.3% were lateral, 20.6% epicardial, and 19.9% concentric. We conclude that cCTA can non-invasively study the effect of vascular hemodynamics, such as turbulent flow (bifurcations) and low shear stress (myocardial vessel wall), on the distribution and composition of atherosclerotic plaque deposition. (orig.)

  5. Meniscal Ramp Lesions

    Science.gov (United States)

    Chahla, Jorge; Dean, Chase S.; Moatshe, Gilbert; Mitchell, Justin J.; Cram, Tyler R.; Yacuzzi, Carlos; LaPrade, Robert F.

    2016-01-01

    Meniscal ramp lesions are more frequently associated with anterior cruciate ligament (ACL) injuries than previously recognized. Some authors suggest that this entity results from disruption of the meniscotibial ligaments of the posterior horn of the medial meniscus, whereas others support the idea that it is created by a tear of the peripheral attachment of the posterior horn of the medial meniscus. Magnetic resonance imaging (MRI) scans have been reported to have a low sensitivity, and consequently, ramp lesions often go undiagnosed. Therefore, to rule out a ramp lesion, an arthroscopic evaluation with probing of the posterior horn of the medial meniscus should be performed. Several treatment options have been reported, including nonsurgical management, inside-out meniscal repair, or all-inside meniscal repair. In cases of isolated ramp lesions, a standard meniscal repair rehabilitation protocol should be followed. However, when a concomitant ACL reconstruction (ACLR) is performed, the rehabilitation should follow the designated ACLR postoperative protocol. The purpose of this article was to review the current literature regarding meniscal ramp lesions and summarize the pertinent anatomy, biomechanics, diagnostic strategies, recommended treatment options, and postoperative protocol. PMID:27504467

  6. Monitoring pigmented skin lesions

    Science.gov (United States)

    Wallace, Vincent P.; Bamber, Jeffery C.; Ott, Robert J.; Crawford, Diane C.; Mortimer, Peter S.

    2002-06-01

    The rising incidence of skin cancer has led to an increase in the number of patients with skin lesions that require diagnosis, mostly using subjective visual examination. Successful treatment depends on early diagnosis. Unfortunately diagnostic accuracy, even by experts, can be as low as 56%; therefore, an accurate, objective diagnostic aid is greatly needed. Reflectance characteristics of pigmented skin lesions were documented to evaluate their diagnostic potential. Reflectance spectra in the wavelength range 320-1100nm were obtained from 260 lesions. Differences between spectra from benign and malignant lesions were utilized by extracting features with the best discriminating power. Discrimination was evaluated using two techniques: multivariate statistical analysis and artificial neural networks, using histology as the standard. Each technique was tested in a blind study and assessed in terms of its ability to diagnose new cases and compared to the clinical diagnosis. The artificial neural network achieved the best diagnostic performance for discriminating between malignant melanoma and benign nevi, having a sensitivity of 100% and a specificity of 65%. Utilization of visible and infrared techniques for monitoring skin lesions has lead to improvements in diagnostic accuracy. We conclude that these techniques are worthy of further development and evaluation in clinical practice as a screening tool.

  7. Non-invasive evaluation of culprit lesions by PET imaging: shifting the clinical paradigm away from resultant anatomy toward causative physiology

    OpenAIRE

    Caobelli, Federico; Bengel, Frank M.

    2014-01-01

    Although coronary angiography is the gold standard for assessing coronary artery disease (CAD), there is at best a weak correlation between degree of stenosis and the risk of developing cardiac events. Plaque rupture is the most common type of plaque complication, accounting for about 70% of fatal acute myocardial infarctions or sudden coronary deaths. Recently, the feasibility of 18F-fluoride PET/CT in the evaluation of atherosclerotic lesions was assessed. Radionuclide techniques allow non-...

  8. Suspected Acoustic Neuroma Demyelinating Lesions.

    Science.gov (United States)

    Zhou, Xiuming; Wang, Xiang; Zhang, Xiejun; Wu, Qiang; Huang, Guodong; Li, Weiping

    2016-11-01

    Demyelinating lesions were recognized as a kind of rare central nervous system demyelinating lesion. The diagnosis and differential diagnosis of demyelinating lesions is difficult. Once the diagnosis was delayed or incorrect, it will make a great impact on patients.Demyelinating lesions often involved in young and middle-aged, but this patient was the aged, which is rare.

  9. Vaccinia virus A43R gene encodes an orthopoxvirus-specific late non-virion type-1 membrane protein that is dispensable for replication but enhances intradermal lesion formation.

    Science.gov (United States)

    Sood, Cindy L; Moss, Bernard

    2010-01-05

    The vaccinia virus A43R open reading frame encodes a 168-amino acid protein with a predicted N-terminal signal sequence and a C-terminal transmembrane domain. Although A43R is conserved in all sequenced members of the orthopoxvirus genus, no non-orthopoxvirus homolog or functional motif was recognized. Biochemical and confocal microscopic studies indicated that A43 is expressed at late times following viral DNA synthesis and is a type-1 membrane protein with two N-linked oligosaccharide chains. A43 was present in Golgi and plasma membranes but only a trace amount was detected in sucrose gradient purified mature virions and none in CsCl gradient purified enveloped virions. Prevention of A43R expression had no effect on plaque size or virus replication in cell culture and little effect on virulence after mouse intranasal infection. Although the A43 mutant produced significantly smaller lesions in skin of mice than the control, the amounts of virus recovered from the lesions were similar.

  10. Effect of AVE 0991 angiotensin-(1-7) receptor agonist treatment on elemental and biomolecular content and distribution in atherosclerotic plaques of apoE-knockout mice

    Science.gov (United States)

    Kowalska, J.; Gajda, M.; Jawień, J.; Kwiatek, W. M.; Appel, K.; Dumas, P.

    2013-12-01

    Gene-targeted apolipoprotein E-knockout (apoE-KO) mice display early and highly progressive vascular lesions containing lipid deposits and they became a reliable animal model to study atherosclerosis. The aim of the present study was to investigate the effect of AVE 0991 angiotensin-(1-7) receptor agonist on the distribution of selected pro- and anti- inflammatory elements as well as biomolecules in atherosclerotic plaques of apoE-knockout mice. Synchrotron radiation-based X-ray fluorescence (micro-XRF) and Fourier Transform Infrared (micro-FTIR) microspectroscopies were applied. Two-month-old apoE-KO mice were fed for following four months diet supplemented with AVE 0991 (0.58 μmol/kg b.w. per day). Histological sections of ascending aortas were analyzed spectroscopically. The distribution of P, Ca, Fe and Zn were found to correspond with histological structure of the lesion. Significantly lower contents of P, Ca, Zn and significantly higher content of Fe were observed in animals treated with AVE 0991. Biomolecular analysis showed lower lipids saturation level and lower lipid to protein ratio in AVE 0991 treated group. Protein secondary structure was studied according to the composition of amide I band (1660 cm-1) and it demonstrated higher proportion of β-sheet structure as compared to α-helix in both studied groups.

  11. Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability.

    Science.gov (United States)

    Müller, Adrienne; Krämer, Stefanie D; Meletta, Romana; Beck, Katharina; Selivanova, Svetlana V; Rancic, Zoran; Kaufmann, Philipp A; Vos, Bernhard; Meding, Jörg; Stellfeld, Timo; Heinrich, Tobias K; Bauser, Marcus; Hütter, Joachim; Dinkelborg, Ludger M; Schibli, Roger; Ametamey, Simon M

    2014-08-01

    Atherosclerotic plaque rupture is the primary cause for myocardial infarction and stroke. During plaque progression macrophages and mast cells secrete matrix-degrading proteolytic enzymes, such as matrix metalloproteinases (MMPs). We studied levels of MMPs and tissue inhibitor of metalloproteinases-3 (TIMP-3) in relation to the characteristics of carotid plaques. We evaluated in vitro two radiolabeled probes targeting active MMPs towards non-invasive imaging of rupture-prone plaques. Human carotid plaques obtained from endarterectomy were classified into stable and vulnerable by visual and histological analysis. MMP-1, MMP-2, MMP-8, MMP-9, MMP-10, MMP-12, MMP-14, TIMP-3, and CD68 levels were investigated by quantitative polymerase chain reaction. Immunohistochemistry was used to localize MMP-2 and MMP-9 with respect to CD68-expressing macrophages. Western blotting was applied to detect their active forms. A fluorine-18-labeled MMP-2/MMP-9 inhibitor and a tritiated selective MMP-9 inhibitor were evaluated by in vitro autoradiography as potential lead structures for non-invasive imaging. Gene expression levels of all MMPs and CD68 were elevated in plaques. MMP-1, MMP-9, MMP-12 and MMP-14 were significantly higher in vulnerable than stable plaques. TIMP-3 expression was highest in stable and low in vulnerable plaques. Immunohistochemistry revealed intensive staining of MMP-9 in vulnerable plaques. Western blotting confirmed presence of the active form in plaque lysates. In vitro autoradiography showed binding of both inhibitors to stable and vulnerable plaques. MMPs differed in their expression patterns among plaque phenotypes, providing possible imaging targets. The two tested MMP-2/MMP-9 and MMP-9 inhibitors may be useful to detect atherosclerotic plaques, but not the vulnerable lesions selectively. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Perilipin1 deficiency in whole body or bone marrow-derived cells attenuates lesions in atherosclerosis-prone mice.

    Directory of Open Access Journals (Sweden)

    Xiaojing Zhao

    Full Text Available The objective of this study is to determine the role of perilipin 1 (Plin1 in whole body or bone marrow-derived cells on atherogenesis.Accumulated evidence have indicated the role of Plin1 in atherosclerosis, however, these findings are controversial. In this study, we showed that Plin1 was assembled and colocalized with CD68 in macrophages in atherosclerotic plaques of ApoE-/- mice. We further found 39% reduction of plaque size in the aortic roots of Plin1 and ApoE double knockout (Plin1-/-ApoE-/- females compared with ApoE-/- female littermates. In order to verify whether this reduction was macrophage-specific, the bone marrow cells from wild-type or Plin1 deficient mice (Plin1-/- were transplanted into LDL receptor deficient mice (LDLR-/-. Mice receiving Plin1-/- bone marrow cells showed also 49% reduction in aortic atherosclerotic lesions compared with LDLR-/- mice received wild-type bone marrow cells. In vitro experiments showed that Plin1-/- macrophages had decreased protein expression of CD36 translocase and an enhanced cholesterol ester hydrolysis upon aggregated-LDL loading, with unaltered expression of many other regulators of cholesterol metabolism, such as cellular lipases, and Plin2 and 3. Given the fundamental role of Plin1 in protecting LD lipids from lipase hydrolysis, it is reasonably speculated that the assembly of Plin1 in microphages might function to reduce lipolysis and hence increase lipid retention in ApoE-/- plaques, but this pro-atherosclerotic property would be abrogated on inactivation of Plin1.Plin1 deficiency in bone marrow-derived cells may be responsible for reduced atherosclerotic lesions in the mice.

  13. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Ida Rune

    Full Text Available The importance of the gut microbiota (GM in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD, and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/- mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis

  14. Lowbush blueberries inhibit scavenger receptors CD36 and SR-A expression and attenuate foam cell formation in ApoE-deficient mice

    Science.gov (United States)

    Blueberries have recently been reported to reduce atherosclerotic lesion progression in apoE deficient (apoE-/-) mice. However, the underlying mechanisms are not fully understood. The objective of this study was to determine whether blueberries altered scavenger receptors expression and foam cell fo...

  15. Mallory-Weiss lesions

    DEFF Research Database (Denmark)

    Lange, J.; Jensen, Lone Susanne

    2010-01-01

    Introduction: Malory-Weiss syndrome (MW) has been known since 1929. Only few studies exist which focus on the prognosis of the lesion. No Danish MW data are available. The purpose of the study was to describe the demographics of patients admitted with an MW to a Danish surgical unit during a 5-year...

  16. Common conjunctival lesions

    African Journals Online (AJOL)

    where vision is affected, if the pterygium looks suspicious or if it is cosmetically unacceptable. Limbal dermoid (Fig. 6). A limbal dermoid is a congenital tumour that usually occurs at the inferotemporal limbus or globe. ... Such lesions may be multiple and appear in the caruncle or fornix. e sessile papilloma is more frequently ...

  17. White matter lesion progression

    DEFF Research Database (Denmark)

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C

    2015-01-01

    BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants asso...

  18. Managing Carious Lesions

    DEFF Research Database (Denmark)

    Schwendicke, F; Frencken, J E; Bjørndal, L

    2016-01-01

    or permanent teeth,selective removal to soft dentineshould be performed, although in permanent teeth,stepwise removalis an option. The evidence and, therefore, these recommendations support less invasive carious lesion management, delaying entry to, and slowing down, the restorative cycle by preserving tooth...

  19. Genital lesions following bestiality

    Directory of Open Access Journals (Sweden)

    Mittal A

    2000-01-01

    Full Text Available A 48-year-old man presented with painful genital lesions with history of bestiality and abnor-mal sexual behaviour. Examination revealed multiple irregular tender ulcers and erosions, with phimosis and left sided tender inguinal adenopathy. VDRL, TPHA, HIV-ELISA were negative. He was treated with ciprofloxacin 500mg b.d. along with saline compresses with complete resolution.

  20. Selective expansion of influenza A virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques

    NARCIS (Netherlands)

    T.T. Keller (Tymen); J.J. van der Meer (Jelger); P. Teeling (Peter); K.F. van der Sluijs (Koenraad); M.M. Idu (Mirza); G.F. Rimmelzwaan (Guus); M. Levi (Michael); A.C. van der Wal (Allard); O.J. de Boer (Onno)

    2008-01-01

    textabstractBACKGROUND AND PURPOSE - Evidence is accumulating that infection with influenza A virus contributes to atherothrombotic disease. Vaccination against influenza decreases the risk of atherosclerotic syndromes, indicating that inflammatory mechanisms may be involved. We tested the

  1. Cohort study of predictive value of urinary albumin excretion for atherosclerotic vascular disease in patients with insulin dependent diabetes

    DEFF Research Database (Denmark)

    Deckert, T; Yokoyama, H; Mathiesen, E

    1996-01-01

    OBJECTIVE: To examine whether slightly elevated urinary albumin excretion precedes development of atherosclerotic vascular disease in patients with insulin dependent diabetes independently of conventional atherogenic risk factors and of diabetic nephropathy. DESIGN: Cohort study with 11 year follow......, smoking habits, and serum concentrations of total cholesterol, high density lipoprotein cholesterol, sialic acid, and von Willebrand factor. END POINT: atherosclerotic vascular disease assessed by death certificates, mailed questionnaires, and hospital records. RESULTS: Thirty patients developed...... atherosclerotic vascular disease during follow up of 2457 person year. Elevated urinary albumin excretion was significantly predictive of atherosclerotic vascular disease (hazard ratio 1.06 (95% confidence interval 1.02 to 1.18) per 5 mg increase in 24 hour urinary albumin excretion, P = 0.002). Predictive effect...

  2. Morel-Lavallee lesion.

    Science.gov (United States)

    Li, Hui; Zhang, Fangjie; Lei, Guanghua

    2014-01-01

    To review current knowledge of the Morel-Lavallee lesion (MLL) to help clinicians become familiar with this entity. Familiarization may decrease missed diagnoses and misdiagnoses. It could also help steer the clinician to the proper treatment choice. A search was performed via PubMed and EMBASE from 1966 to July 2013 using the following keywords: Morel-Lavallee lesion, closed degloving injury, concealed degloving injury, Morel-Lavallee effusion, Morel-Lavallee hematoma, posttraumatic pseudocyst, posttraumatic soft tissue cyst. Chinese and English language literatures relevant to the subject were collected. Their references were also reviewed. Morel-Lavallee lesion is a relatively rare condition involving a closed degloving injury. It is characterized by a filled cystic cavity created by separation of the subcutaneous tissue from the underlying fascia. Apart from the classic location over the region of the greater trochanter, MLLs have been described in other parts of the body. The natural history of MLL has not yet been established. The lesion may decrease in volume, remain stable, enlarge progressively or show a recurrent pattern. Diagnosis of MLL was often missed or delayed. Ultrasonography, computed tomography, and magnetic resonance imaging have great value in the diagnosis of MLL. Treatment of MLL has included compression, local aspiration, open debridement, and sclerodesis. No standard treatment has been established. A diagnosis of MLL should be suspected when a soft, fluctuant area of skin or chronic recurrent fluid collection is found in a region exposed to a previous shear injury. Clinicians and radiologists should be aware of both the acute and chronic appearances to make the correct diagnosis. Treatment decisions should base on association with fractures, the condition of the lesion, symptom and desire of the patient.

  3. Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR -/- mice.

    Science.gov (United States)

    Gajda, Mariusz; Jawień, Jacek; Mateuszuk, Lukasz; Lis, Grzegorz J; Radziszewski, Andrzej; Chłopicki, Stefan; Litwin, Jan A

    2008-01-01

    This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA), macrophages (rat anti-CD68) and T lymphocytes (rabbit anti-CD3). Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment.

  4. Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR -/- mice.

    Directory of Open Access Journals (Sweden)

    Stefan Chłopicki

    2008-06-01

    Full Text Available This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/- mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA, macrophages (rat anti-CD68 and T lymphocytes (rabbit anti-CD3. Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment.

  5. Atherosclerotic plaque component segmentation in combined carotid MRI and CTA data incorporating class label uncertainty

    DEFF Research Database (Denmark)

    van Engelen, Arna; Niessen, Wiro J.; Klein, Stefan

    2014-01-01

    Atherosclerotic plaque composition can indicate plaque vulnerability. We segment atherosclerotic plaque components from the carotid artery on a combination of in vivo MRI and CT-angiography (CTA) data using supervised voxelwise classification. In contrast to previous studies the ground truth...... for training is directly obtained from 3D registration with histology for fibrous and lipid-rich necrotic tissue, and with [Formula: see text]CT for calcification. This registration does, however, not provide accurate voxelwise correspondence. We therefore evaluate three approaches that incorporate uncertainty...... in the ground truth used for training: I) soft labels are created by Gaussian blurring of the original binary histology segmentations to reduce weights at the boundaries between components, and are weighted by the estimated registration accuracy of the histology and in vivo imaging data (measured by overlap...

  6. A case of atherosclerotic inferior mesenteric artery aneurysm secondary to high flow state.

    Science.gov (United States)

    Troisi, Nicola; Esposito, Giovanni; Cefalì, Pietro; Setti, Marco

    2011-07-01

    Inferior mesenteric artery aneurysms are very rare and they are among the rarest of visceral artery aneurysms. Sometimes, the distribution of the blood flow due to chronic atherosclerotic occlusion of some arteries can establish an increased flow into a particular supplying district (high flow state). A high flow state in a stenotic inferior mesenteric artery in compensation for a mesenteric occlusive disease can produce a rare form of aneurysm. We report the case of an atherosclerotic inferior mesenteric aneurysm secondary to high flow state (association with occlusion of the celiac trunk and severe stenosis of the superior mesenteric artery), treated by open surgical approach. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  7. Research progress of noninvasive high - resolution magnetic resonance imaging in carotid atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Peng GAO

    2017-07-01

    Full Text Available Carotid atherosclerotic stenosis is closely related to recurrent ischemic stroke. Currently, therapies for carotid artery stenosis are mainly intensive medication or surgery, including carotid artery stenting (CAS and carotid endarterectomy (CEA. The prevention of stroke lies in identifying risk factors for carotid artery stenosis, screening patients with high risk of recurrent stroke, so as to benefit from medication or surgery. However, therapeutic schedule is formulated only according to the degrees of carotid artery stenosis, and there lacks of individualized treatment. Recently, new imaging modalities, such as noninvasive high.resolution MRI (HRMRI could detect the vulnerability of carotid atherosclerotic plaque. Compared with the degree of carotid artery stenosis measured by conventional DSA, noninvasive HRMRI can precisely predict the risk of ipsilateral stroke according to plaque morphology, so as to guide individualized treatment. DOI: 10.3969/j.issn.1672-6731.2017.05.012

  8. Simultaneous two-photon imaging of cerebral oxygenation and capillary blood flow in atherosclerotic mice

    Science.gov (United States)

    Lu, Xuecong; Li, Baoqiang; Moeini, Mohammad; Lesage, Frédéric

    2017-02-01

    Gradual changes in brain microvasculature and cerebral capillary blood flow occurring with atherosclerosis may significantly contribute to cognition decline due to their role in brain tissue oxygenation. However, previous stud- ies of the relationship between cerebral capillary blood flow and brain tissue oxygenation are limited. This study aimed to investigate vascular and concomitant changes in brain tissue pO2 with atherosclerosis. Experiments in young healthy C57B1/6 mice (n=6 , WT), young atherosclerotic mice (n=6 , ATX Y) and old atherosclerotic mice (n=6 , ATX O) were performed imaging on the left sensory-motor cortex at resting state under urethane (1.5 g/kg) anesthesia using two-photon fluorescence microscopy. The results showed that pO2 around capillaries, correlated with red blood cell (RBC) flux, increased with atherosclerosis.

  9. Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

    DEFF Research Database (Denmark)

    Barascuk, Natasha; Skjøt-Arkil, Helene; Register, Thomas C

    2010-01-01

    BACKGROUND: Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular......-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women...... with aortic calcifications compared to those without. CONCLUSIONS: Human macrophage foam cells degrade the atherosclerotic plaques though cathepsin K mediated processes, resulting in increase in levels of CTX-I. Serum CTX-I was not elevated in women with aortic calcification, likely due to the contribution...

  10. The effect of aging on atherosclerotic plaque inflammation and molecular calcification: A PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Simonsen, Jane Angel

    Aim: Aging is an important independent risk factor for the inception and maturation of atherosclerotic plaques. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and molecular calcification. Methods: Thirteen healthy volunteers without traditional...... polynomial regression established that aging is a strong predictor of the degree of aortic plaque inflammation (R2 = 0.71, F statistic = 11.98, P = 0.002). A linear relationship was observed between aging and molecular calcification. Linear regression established that aging is a predictor of both the degree.......001). Conclusions: Based on preliminary data, a quadratic relationship appears to exist between aging and plaque inflammation. In contrast, a linear relationship was observed between aging and plaque molecular calcification. These data reject the existence of a linear relationship between plaque inflammation...

  11. Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR -/- mice.

    OpenAIRE

    Stefan Chłopicki; Andrzej Radziszewski; Grzegorz J Lis; Lukasz Mateuszuk; Jacek Jawień; Mariusz Gajda; Jan A Litwin

    2008-01-01

    This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA), macrophages (rat anti-CD68) and T...

  12. Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

    Science.gov (United States)

    2015-01-01

    Background Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue. Methods Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue. Results Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen. Conclusions Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large

  13. Weight loss therapy for clinical management of patients with some atherosclerotic diseases: a randomized clinical trial

    OpenAIRE

    Oshakbayev, Kuat; Dukenbayeva, Bibazhar; Otarbayev, Nurzhan; Togizbayeva, Gulnar; Tabynbayev, Nariman; Gazaliyeva, Meruyert; Idrisov, Alisher; Oshakbayev, Pernekul

    2015-01-01

    Background The prevalence and burden of atherosclerotic (AS) diseases are increasing during the last twenty years. Some studies show a close relationship between overweight and AS, but influence on AS diseases of different weight loss methods are still studying. The purpose of the research was to study the effectiveness of a weight loss program in AS patients in randomized controlled trial, and to develop a conception of evolution of AS. Methods A randomized controlled prospective clinical tr...

  14. A Quantitative Model of Early Atherosclerotic Plaques Parameterized Using In Vitro Experiments.

    Science.gov (United States)

    Thon, Moritz P; Ford, Hugh Z; Gee, Michael W; Myerscough, Mary R

    2018-01-01

    There are a growing number of studies that model immunological processes in the artery wall that lead to the development of atherosclerotic plaques. However, few of these models use parameters that are obtained from experimental data even though data-driven models are vital if mathematical models are to become clinically relevant. We present the development and analysis of a quantitative mathematical model for the coupled inflammatory, lipid and macrophage dynamics in early atherosclerotic plaques. Our modeling approach is similar to the biologists' experimental approach where the bigger picture of atherosclerosis is put together from many smaller observations and findings from in vitro experiments. We first develop a series of three simpler submodels which are least-squares fitted to various in vitro experimental results from the literature. Subsequently, we use these three submodels to construct a quantitative model of the development of early atherosclerotic plaques. We perform a local sensitivity analysis of the model with respect to its parameters that identifies critical parameters and processes. Further, we present a systematic analysis of the long-term outcome of the model which produces a characterization of the stability of model plaques based on the rates of recruitment of low-density lipoproteins, high-density lipoproteins and macrophages. The analysis of the model suggests that further experimental work quantifying the different fates of macrophages as a function of cholesterol load and the balance between free cholesterol and cholesterol ester inside macrophages may give valuable insight into long-term atherosclerotic plaque outcomes. This model is an important step toward models applicable in a clinical setting.

  15. Renal glucosuria is not associated with atherosclerotic cardiovascular disease outcome in a general Japanese community.

    Science.gov (United States)

    Tada, Hayato; Kawashiri, Masa-Aki; Sakata, Kenji; Yoneda, Takashi; Yasuda, Kenji; Yamagishi, Masakazu; Hayashi, Kenshi

    2017-06-01

    Renal glucosuria is defined as the excretion of detectable amounts of glucose in the urine without diabetes or hyperglycemia. Few data exist regarding the prevalence of renal glucosuria and its clinical impact on atherosclerotic cardiovascular diseases. This study included 47,842 subjects (16,913 men, 35.4%) aged ≥40 years who underwent the Japanese specific health checkup in Kanazawa City during 2014. We defined renal glucosuria as fulfillment of all of the following three criteria: 1) detectable glucosuria; 2) the absence of diabetes; 3) normal blood glucose (renal glucosuria and of factors associated with atherosclerotic cardiovascular diseases, including coronary artery disease and stroke, was assessed. The criteria for renal glucosuria were met by 665 (1.4%) subjects. Significantly higher proportions of subjects with renal glucosuria exhibited coronary artery disease, stroke, or either outcome than those without (14.9% vs. 12.1%, p = 0.0305; 9.9% vs. 6.9%, p = 0.00255; 22.3% vs. 17.0%, p = 4.0 × 10-4, respectively), but multivariate logistic regression analyses revealed that renal glucosuria was not associated with coronary artery disease (odds ratio [OR] = 0.940, 95% confidence interval [CI] = 0.748-1.171, not significant), stroke (OR = 1.122, 95% CI = 0.853-1.453, not significant), or atherosclerotic cardiovascular diseases (OR = 1.122, 95% CI = 0.853-1.453, not significant). These results indicate that the prevalence of renal glucosuria in the Japanese general population was 1.4%, and that renal glucosuria was not associated with atherosclerotic cardiovascular diseases per se. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Association of Thrombomodulin Gene Polymorphisms with Susceptibility to Atherosclerotic Diseases: A Meta-Analysis.

    Science.gov (United States)

    Xu, Jie; Jin, Jun; Tan, Sheng

    2016-05-01

    Previous studies have proved that the dysfunction of thrombomodulin (TM) plays an important role in the pathogenesis of atherosclerotic diseases. In order to reveal their inherent relationship, we conducted a meta-analysis to uncover the association between two polymorphisms -33G/A and Ala455Val (c.1418C>T) in the TM gene and atherosclerotic diseases. We carried out a systematic search in PubMed, Science Direct, BIOSIS Previews, SpringerLink, the Cochrane library, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Database, the Wei Pu database, and the Wanfang Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed to show the association. We included 22 eligible studies which involved 5472 patients and 7786 controls. There were statistically significant associations between -33G/A polymorphisms in TM and the MI group under the Allele and Recessive models in Asians (G vs. A: OR = 0.67, 95%CI = 0.56-0.78, P < 0.00001; GG vs. GA+AA: OR = 0.66, 95%CI = 0.56-0.78, P < 0.00001). However, these findings of the overall and subgroups showed that Ala455Val polymorphisms did not have any relationship with atherosclerotic diseases. After Bonferroni correction, the above associations remained statistically significant. This meta-analysis provides robust evidence of association between the -33G/A polymorphism in the TM gene and the risk of myocardial infarction in Asians. The A allele may increase the incidence of MI in Asians. However, the Ala455Val variant was not associated with atherosclerotic risk. Further studies with adequate sample size are needed to verify our findings. © 2016 John Wiley & Sons Ltd/University College London.

  17. Ex-vivo UV autofluorescence imaging and fluorescence spectroscopy of atherosclerotic pathology in human aorta

    Science.gov (United States)

    Lewis, William; Williams, Maura; Franco, Walfre

    2017-02-01

    The aim of our study was to identify fluorescence excitation-emission pairs correlated with atherosclerotic pathology in ex-vivo human aorta. Wide-field images of atherosclerotic human aorta were captured using UV and visible excitation and emission wavelength pairs of several known fluorophores to investigate correspondence with gross pathologic features. Fluorescence spectroscopy and histology were performed on 21 aortic samples. A matrix of Pearson correlation coefficients were determined for the relationship between relevant histologic features and the intensity of emission for 427 wavelength pairs. A multiple linear regression analysis indicated that elastin (370/460 nm) and tryptophan (290/340 nm) fluorescence predicted 58% of the variance in intima thickness (R-squared = 0.588, F(2,18) = 12.8, p=.0003), and 48% of the variance in media thickness (R-squared = 0.483, F(2,18) = 8.42, p=.002), suggesting that endogenous fluorescence intensity at these wavelengths can be utilized for improved pathologic characterization of atherosclerotic plaques.

  18. Role of infrasound pressure waves in atherosclerotic plaque rupture: a theoretical approach.

    Science.gov (United States)

    Tsatsaris, Athanasios; Koukounaris, Efstathios; Motsakos, Theodoros; Perrea, Despina

    2007-01-01

    To investigate the role of infrasound aortic pressure waves (IPW) in atherosclerotic plaque rupture. Atherosclerotic plaques have been simulated partly, in two dimensions, as being short or long Conical Intersections (CIS), that is to say elliptic, parabolic or hyperbolic surfaces. Consequently, the course and reflection of the generated aortic pressure wave (infrasound domain-less than 20Hz) has been examined around the simulated plaques. The incidence of IPW on plaque surface results both in reflection and "refraction" of the wave. The IPW course within tissue, seems to be enhanced by high Cu-level presence at these areas according to recent evidence (US2003000388213). The "refracted", derived wave travels through plaque tissue and is eventually accumulated to the foci of the respective CIS-plaque geometry. The foci location within or underneath atheroma declares zones where infrasound energy is mostly absorbed. This process, among other mechanisms may contribute to plaque rupture through the development of local hemorrhage and inflammation in foci areas. In future, detection of foci areas and repair (i.e. via Laser Healing Microtechnique) may attenuate atherosclerotic plaque rupture behavior.

  19. Ex vivo detection of macrophages in atherosclerotic plaques using intravascular ultrasonic-photoacoustic imaging

    Science.gov (United States)

    Quang Bui, Nhat; Hlaing, Kyu Kyu; Lee, Yong Wook; Kang, Hyun Wook; Oh, Junghwan

    2017-01-01

    Macrophages are excellent imaging targets for detecting atherosclerotic plaques as they are involved in all the developmental stages of atherosclerosis. However, no imaging technique is currently capable of visualizing macrophages inside blood vessel walls. The current study develops an intravascular ultrasonic-photoacoustic (IVUP) imaging system combined with indocyanine green (ICG) as a contrast agent to provide morphological and compositional information about the targeted samples. Both tissue-mimicking vessel phantoms and atherosclerotic plaque-mimicking porcine arterial tissues are used to demonstrate the feasibility of mapping macrophages labeled with ICG by endoscopically applying the proposed hybrid technique. A delay pulse triggering technique is able to sequentially acquire photoacoustic (PA) and ultrasound (US) signals from a single scan without using any external devices. The acquired PA and US signals are used to reconstruct 2D cross-sectional and 3D volumetric images of the entire tissue with the ICG-loaded macrophages injected. Due to high imaging contrast and sensitivity, the IVUP imaging vividly reveals structural information and detects the spatial distribution of the ICG-labeled macrophages inside the samples. ICG-assisted IVUP imaging can be a feasible imaging modality for the endoscopic detection of atherosclerotic plaques.

  20. Stages of change for fruit and vegetable intake among patients with atherosclerotic disease.

    Science.gov (United States)

    Bernardes, Simone; Caramori, Paulo Ricardo A

    2011-12-01

    This paper describes the stages of change in fruit and vegetable intake among patients with atherosclerotic disease, identifying demographic, socioeconomic, and health predictive factors for each stage of change. It is a cross-sectional study of 290 consecutive patients with atherosclerotic disease submitted to endovascular procedures in two referral hospitals. The staging algorithm included intentional and behavioral criteria, and patients were categorized into "pre-action" (pre-contemplation, contemplation, and preparation), or "action" (action, non-reflective action, and maintenance). Most of the patients were in action for the fruits intake (67.9%) and pre-action for the vegetables intake (69.1%). The logistic regression analysis for the stages of action change for fruits intake has identified as predictive factors, the higher level of education and consultation with a cardiologist. For the stages of action change for vegetable intake, absence of abdominal obesity, previous cardiac surgery, and consultation with dietitian have shown significant association. This study has shown differences in the distribution of stages of change for the fruits and vegetable intake among the patients with atherosclerotic disease. The different predictive factors for the stage of changes for fruits and vegetables suggest that approaches of nutritional orientation of the individuals must be distinct for each eating behavior. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Primary stenting in the treatment of focal atherosclerotic abdominal aortic stenoses

    Energy Technology Data Exchange (ETDEWEB)

    Poncyljusz, W.; Falkowski, A.; Garncarek, J.; Karasek, M.; England, S.; Zawierucha, D

    2006-08-15

    Aim: To evaluate the results of primary stent placement in focal atherosclerotic aortic stenoses using balloon expandable stents. Materials and methods: Twenty-six primary balloon expandable stent placements in the abdominal aorta were performed and reviewed. All the aortic stenoses were atherosclerotic. Patients were followed up by ankle/brachial pressure indices (ABPI) and Doppler ultrasound (US) at 24 h after procedure and at 12 and 24 months. Follow-up angiograms were performed at 12 months. Results: Twenty-six stents in 26 patients were placed in the infrarenal aorta. All procedures were technically successful and immediate clinical success was obtained. The mean ABPI significantly improved from 0.52 {+-} 0.10 to 0.94 {+-} 0.09 within 24 h after procedure, and remained at 0.90 {+-} 0.12 between 12 and 24 months follow-up (mean 18 months). There was full haemodynamic success at hospital discharge and at 12 and 24 months after the procedure. Clinical success at 12 and 24 months (mean 18 months) was defined as an improvement in the Fontaine classification by at least one class compared with the pre-procedure class and was shown to be 100%. Conclusion: In summary, we report that primary stenting is a safe and effective alternative to surgery in cases of symptomatic stenosis of the infrarenal abdominal aorta. The excellent intermediate term results suggested that we would recommend primary stenting as the treatment of choice for focal atherosclerotic stenoses of the infrarenal aorta in selected patients.

  2. Primary stenting in the treatment of focal atherosclerotic abdominal aortic stenoses.

    Science.gov (United States)

    Poncyljusz, W; Falkowski, A; Garncarek, J; Karasek, M; England, S; Zawierucha, D

    2006-08-01

    To evaluate the results of primary stent placement in focal atherosclerotic aortic stenoses using balloon expandable stents. Twenty-six primary balloon expandable stent placements in the abdominal aorta were performed and reviewed. All the aortic stenoses were atherosclerotic. Patients were followed up by ankle/brachial pressure indices (ABPI) and Doppler ultrasound (US) at 24h after procedure and at 12 and 24 months. Follow-up angiograms were performed at 12 months. Twenty-six stents in 26 patients were placed in the infrarenal aorta. All procedures were technically successful and immediate clinical success was obtained. The mean ABPI significantly improved from 0.52+/-0.10 to 0.94+/-0.09 within 24h after procedure, and remained at 0.90+/-0.12 between 12 and 24 months follow-up (mean 18 months). There was full haemodynamic success at hospital discharge and at 12 and 24 months after the procedure. Clinical success at 12 and 24 months (mean 18 months) was defined as an improvement in the Fontaine classification by at least one class compared with the pre-procedure class and was shown to be 100%. In summary, we report that primary stenting is a safe and effective alternative to surgery in cases of symptomatic stenosis of the infrarenal abdominal aorta. The excellent intermediate term results suggested that we would recommend primary stenting as the treatment of choice for focal atherosclerotic stenoses of the infrarenal aorta in selected patients.

  3. BENIGN LESIONS OF MANDIBLE ON ORTHOPANTOMOGRAM- OUR EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Raseshkumar Rasiklal Vyas

    2017-03-01

    Full Text Available BACKGROUND Orthopantomography plays a vital role to diagnose mandibular lesions. Odontogenic benign tumours may occur at any period of odontogenesis. Those who develop during first stage of teeth formation do not contain calcified tissue and are therefore referred to as soft. When they develop during second stage (formation of enamel and cementum they may contain calcified tissue so known as hard lesion. Orthopantomography help in such a way that tissue biopsy is necessary only to confirm the diagnosis and in some case its need may be altogether eliminated. MATERIALS AND METHODS Patients included in the study were from all age groups and under following clinical findings like pain, difficulty to open mouth, swelling, local tenderness, discharge from mouth etc. The machine use for the study is D B Troniks and the duration of the study is one year from jan-2016 to dec-2016. RESULTS A study carried out of 50 patient, after orthopantomogram found that incidence of male are more affected compare to females and most of them lying in third decade. The density of lesions were lytic followed by mixed and then sclerotic, while the margins of most of the lesions was smooth and well define. Most common lesion was dentigerous cyst followed by radicular cyst. CONCLUSION Many lesions involving the jaw produce characteristic radiographic appearances while many lesions produce protean characteristic with resultant overlap in radiographic features. With the combine help of history, clinical examination and orthopentomographical examination one can have accurate diagnosis of the lesions.

  4. Lesion progression in post-treatment persistent endodontic lesions.

    Science.gov (United States)

    Yu, Victoria Soo Hoon; Messer, Harold Henry; Shen, Liang; Yee, Robert; Hsu, Chin-ying Stephen

    2012-10-01

    Radiographic lesions related to root-filled teeth may persist for long periods after treatment and are considered to indicate failure of initial treatment. Persistent lesions are found in a proportion of cases, but information on lesion progression is lacking. This study examined the incidence of lesion improvement, remaining unchanged, and deterioration among persistent lesions in a group of patients recruited from a university-based clinic and identified potential predictors for lesion progression. Patients of a university clinic with persistent endodontic lesions at least 4 years since treatment and with original treatment radiographs available were recruited with informed consent. Data were obtained by interview and from dental records and clinical and radiographic examinations. Univariate and multivariate statistical analyses were carried out by using SPSS (version 19). One hundred fifty-one persistent lesions were identified in 114 patients. A majority of the lesions (107, 70.9%) received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%) improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since treatment. Potential predictors for lesions that did not improve included recall lesion size, pain on biting at recall examination, history of a postobturation flare-up, and a non-ideal root-filling length (P < .05). Lesions that had persisted for a longer period appeared less likely to be improving (relative risk, 1.038; 95% confidence interval, 1.000-1.077). A specific time interval alone should not be used to conclude that a lesion will not resolve without intervention. This study identified several clinical factors that are associated with deteriorating persistent lesions, which should aid in identifying lesions that require further intervention. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Meniscal Ramp Lesions

    OpenAIRE

    Chahla, Jorge; Dean, Chase S.; Moatshe, Gilbert; Mitchell, Justin J.; Cram, Tyler R.; Yacuzzi, Carlos; LAPRADE, ROBERT F.

    2016-01-01

    Meniscal ramp lesions are more frequently associated with anterior cruciate ligament (ACL) injuries than previously recognized. Some authors suggest that this entity results from disruption of the meniscotibial ligaments of the posterior horn of the medial meniscus, whereas others support the idea that it is created by a tear of the peripheral attachment of the posterior horn of the medial meniscus. Magnetic resonance imaging (MRI) scans have been reported to have a low sensitivity, and conse...

  6. Skin lesions in sadomasochism.

    Science.gov (United States)

    Sønderbo, K; Nyfors, A

    1986-01-01

    This paper presents the case of a 35-year-old man who consulted the department of venereology because of healing problems with some wounds caused by burning his skin perianally with cigarettes as part of a sexual satisfaction ritual. Knowledge of such lesions may be useful to physicians and social workers. Sadomasochism and 'offers' in the intimate-massage clinics in Copenhagen are surveyed.

  7. Treatment of intracranial atherosclerotic arterial stenoses with a balloon-expandable cobalt chromium stent (Coroflex Blue): procedural safety, efficacy, and midterm patency.

    Science.gov (United States)

    Vajda, Zsolt; Miloslavski, Elina; Güthe, Thomas; Schmid, Elisabeth; Schul, Christoph; Albes, Guido; Henkes, Hans

    2010-07-01

    We evaluated the coronary balloon-expandable cobalt chromium stent Coroflex Blue for the treatment of intracranial atherosclerotic arterial stenoses (IAAS). Between March 2007 and October 2007, a total of 25 patients (20 male, age median 67 years) with 30 IAAS underwent endovascular treatment using Coroflex Blue stents (B. Braun, Germany). Location and degree of target stenoses before and after treatment and at follow-up and adverse clinical sequelae of treatment were registered. Angiographic follow-up was scheduled for 6, 12, 26, and 52 weeks after the treatment. The 30 treated lesions were located as follows: nine in intracranial-extradural internal carotid artery (ICA), three in intradural ICA, five in middle cerebral artery, eight in intradural vertebral artery, and five in basilar artery. The technical success rate was 100%. The degree of stenoses prior to and after treatment was 61 +/- 2% and 26 +/- 3% (mean +/- SE), respectively. A residual stenosis of <50% was achieved in 29 (97%) procedures. Treatment was uneventful in 28 out of 30 procedures (93%); one patient suffered a transient and one patient a permanent neurological deficit. Angiographic follow-up was available in all of the patients (100%) after 15.2 months (median) and showed significant (i.e., more than 50%) degree of recurrent stenosis in 11 (37%) of the lesions. Retreatment was performed in 11 (37%) lesions. The Coroflex Blue stent is easily inserted and safely deployed into intracranial arteries. The incidence of recurrent stenoses remains a concern. Stringent angiographic and clinical follow-up and retreatment are therefore mandatory.

  8. Treatment of intracranial atherosclerotic arterial stenoses with a balloon-expandable cobalt chromium stent (Coroflex Blue): procedural safety, efficacy, and midterm patency

    Energy Technology Data Exchange (ETDEWEB)

    Vajda, Zsolt; Miloslavski, Elina; Albes, Guido [Katharinenhospital - Klinikum Stuttgart, Klinik fuer Neuroradiologie, Stuttgart (Germany); Guethe, Thomas [Katharinenhospital - Klinikum Stuttgart, Klinik fuer Neuroradiologie, Stuttgart (Germany); Katharinenhospital Klinikum, Klinik fuer Neurologie, Stuttgart (Germany); Schmid, Elisabeth [Buergerhospital Klinikum, Klinik fuer Neurologie, Stuttgart (Germany); Schul, Christoph [Katharinenhospital Klinikum, Klinik fuer Neurochirurgie, Stuttgart (Germany); Henkes, Hans [Katharinenhospital - Klinikum Stuttgart, Klinik fuer Neuroradiologie, Stuttgart (Germany); Medizinische Fakultaet der Universitaet, Duisburg-Essen (Germany)

    2010-07-15

    We evaluated the coronary balloon-expandable cobalt chromium stent Coroflex Blue for the treatment of intracranial atherosclerotic arterial stenoses (IAAS). Between March 2007 and October 2007, a total of 25 patients (20 male, age median 67 years) with 30 IAAS underwent endovascular treatment using Coroflex Blue stents (B. Braun, Germany). Location and degree of target stenoses before and after treatment and at follow-up and adverse clinical sequelae of treatment were registered. Angiographic follow-up was scheduled for 6, 12, 26, and 52 weeks after the treatment. The 30 treated lesions were located as follows: nine in intracranial-extradural internal carotid artery (ICA), three in intradural ICA, five in middle cerebral artery, eight in intradural vertebral artery, and five in basilar artery. The technical success rate was 100%. The degree of stenoses prior to and after treatment was 61 {+-} 2% and 26 {+-} 3% (mean {+-} SE), respectively. A residual stenosis of <50% was achieved in 29 (97%) procedures. Treatment was uneventful in 28 out of 30 procedures (93%); one patient suffered a transient and one patient a permanent neurological deficit. Angiographic follow-up was available in all of the patients (100%) after 15.2 months (median) and showed significant (i.e., more than 50%) degree of recurrent stenosis in 11 (37%) of the lesions. Retreatment was performed in 11 (37%) lesions. The Coroflex Blue stent is easily inserted and safely deployed into intracranial arteries. The incidence of recurrent stenoses remains a concern. Stringent angiographic and clinical follow-up and retreatment are therefore mandatory. (orig.)

  9. Formation of canker lesions on stems and black scurf on tubers in experimentally inoculated potato plants by isolates of AG2-1, AG3 and AG5 of Rhizoctonia solani: a pilot study and literature review

    Directory of Open Access Journals (Sweden)

    M.J. LEHTONEN

    2008-12-01

    Full Text Available Development of black scurf on potato tubers (cv. Nicola was compared in plants inoculated with isolates of Rhizoctonia solani of three anastomosis groups (AG2-1, AG3 and AG5 which occur in potato crops in Finland. All isolates induced stem canker lesions but only isolates of AG3 formed efficiently black scurf on progeny tubers. Among the AG2-1 and AG5 isolates tested, only one AG2-1 isolate formed a few sclerotia on 13.5 % of the progeny tubers in one experiment. The data indicate that isolates of AG3 differ from those of AG2-1 and AG5 in having a higher ability to form sclerotia on tubers. Therefore, while AG2-1 and AG5 isolates have a broader host range, AG3 is more efficient in producing black scurf, which provides this anastomosis group with more efficient means of dissemination on seed potatoes. These differences probably explain the predominance of AG3 (98.9 % of isolates in potato crops in Finland and other northern potato production areas.;

  10. Skin lesion removal-aftercare

    Science.gov (United States)

    Shave excision - skin aftercare; Excision of skin lesions - benign aftercare; Skin lesion removal - benign aftercare; Cryosurgery - skin aftercare; BCC - removal aftercare; Basal cell cancer - removal aftercare; Actinic keratosis - removal aftercare; Wart - ...

  11. Morphological classifications of gastrointestinal lesions

    NARCIS (Netherlands)

    Vleugels, Jasper L. A.; Hazewinkel, Yark; Dekker, Evelien

    2017-01-01

    In the era of spreading adoption of gastrointestinal endoscopy screening worldwide, endoscopists encounter an increasing number of complex lesions in the gastrointestinal tract. For decision-making on optimal treatment, precise lesion characterization is crucial. Especially the assessment of

  12. Acute periodontal lesions.

    Science.gov (United States)

    Herrera, David; Alonso, Bettina; de Arriba, Lorenzo; Santa Cruz, Isabel; Serrano, Cristina; Sanz, Mariano

    2014-06-01

    This review provides updates on acute conditions affecting the periodontal tissues, including abscesses in the periodontium, necrotizing periodontal diseases and other acute conditions that cause gingival lesions with acute presentation, such as infectious processes not associated with oral bacterial biofilms, mucocutaneous disorders and traumatic and allergic lesions. A periodontal abscess is clinically important because it is a relatively frequent dental emergency, it can compromise the periodontal prognosis of the affected tooth and bacteria within the abscess can spread and cause infections in other body sites. Different types of abscesses have been identified, mainly classified by their etiology, and there are clear differences between those affecting a pre-existing periodontal pocket and those affecting healthy sites. Therapy for this acute condition consists of drainage and tissue debridement, while an evaluation of the need for systemic antimicrobial therapy will be made for each case, based on local and systemic factors. The definitive treatment of the pre-existing condition should be accomplished after the acute phase is controlled. Necrotizing periodontal diseases present three typical clinical features: papilla necrosis, gingival bleeding and pain. Although the prevalence of these diseases is not high, their importance is clear because they represent the most severe conditions associated with the dental biofilm, with very rapid tissue destruction. In addition to bacteria, the etiology of necrotizing periodontal disease includes numerous factors that alter the host response and predispose to these diseases, namely HIV infection, malnutrition, stress or tobacco smoking. The treatment consists of superficial debridement, careful mechanical oral hygiene, rinsing with chlorhexidine and daily re-evaluation. Systemic antimicrobials may be used adjunctively in severe cases or in nonresponding conditions, being the first option metronidazole. Once the acute

  13. Bacterial biofilm in chronic lesions of hidradenitis suppurativa.

    Science.gov (United States)

    Ring, H C; Bay, L; Nilsson, M; Kallenbach, K; Miller, I M; Saunte, D M; Bjarnsholt, T; Tolker-Nielsen, T; Jemec, G B

    2017-04-01

    Chronic nonhealing or recurrent inflammatory lesions, reminiscent of infection but recalcitrant to antibiotic therapy, generally characterize biofilm-driven diseases. Chronic lesions of hidradenitis suppurativa (HS) exhibit several characteristics, which are compatible with well-known biofilm infections. To determine and quantify the potential presence of bacterial aggregates in chronic HS lesions. In 42 consecutive patients with HS suffering from chronic lesions, biopsies were obtained from lesional as well as from perilesional skin. Samples were investigated using peptide nucleic acid-fluorescence in situ hybridization in combination with confocal laser scanning microscopy. In addition, corresponding histopathological analysis on haematoxylin and eosin slides was performed. Biofilms were seen in 67% of the samples of chronic lesions and in 75% of the perilesional samples. The mean diameter of aggregates in lesional skin was significantly greater than in perilesional skin (P = 0·01). Large biofilms (aggregates > 50 μm in diameter) were found in 42% of lesional samples and in only 5% of the perilesional samples (P = 0·009). The majority of the large biofilms were situated in sinus tracts (63%) or in the infundibulum (37%). The majority of the sinus tract samples (73%) contained active bacterial cells, which were associated with inflammation. This study suggests that biofilm formation is associated with inflammation of chronic HS lesions. The aggregates most likely occur as a secondary event, possibly due to predisposing local anatomical changes such as sinus tracts (tunnels), keratinous detritus and dilated hair follicles. © 2016 British Association of Dermatologists.

  14. A disappearing neonatal skin lesion.

    LENUS (Irish Health Repository)

    Hawkes, Colin Patrick

    2012-01-31

    A preterm baby girl was noted at birth to have a firm, raised, non-tender skin lesion located over her right hip. She developed three similar smaller lesions on her ear, buttock and right knee. All lesions had resolved by 2 months of age.

  15. Early Results with the Use of Heparin-bonded Stent Graft to Rescue Failed Angioplasty of Chronic Femoropopliteal Occlusive Lesions: TASC D Lesions Have a Poor Outcome

    Energy Technology Data Exchange (ETDEWEB)

    Kuhan, Ganesh, E-mail: gkuhan@nhs.net; Abisi, Said; Braithwaite, Bruce D.; MacSweeney, Shane T. R. [Nottingham University Hospitals, Vascular and Endovascular Unit, Queens Medical Centre (United Kingdom); Whitaker, Simon C.; Habib, Said B. [Nottingham University Hospitals, Department of Radiology, Queen' s Medical Centre (United Kingdom)

    2012-10-15

    Purpose: To evaluate early patency rate of the heparin-bonded stent grafts in atherosclerotic long femoropopliteal occlusive disease, and to identify factors that affect outcome. Methods: Heparin-bonded Viabahn stent grafts were placed in 33 limbs in 33 patients during 2009-2010. The stents were deployed to rescue failed conventional balloon angioplasty. Mean age was 69 (range 44-88) years, and 67 % (22 of 33) were men. Most procedures (21 of 33, 64 %) were performed for critical limb ischemia (33 % for rest pain, 30 % tissue loss). Kaplan-Meier plots and Cox regression analysis were used to identify significant risk factors. Results: The average length of lesions treated was 25 {+-} 10 cm, and they were predominantly TASC (Transatlantic Intersociety Consensus) D (n = 13) and C (n = 17) lesions. The median primary patency was 5.0 months (95 % confidence interval 1.22-8.77). The mean secondary patency was 8.6 months (95 % confidence interval 6.82-10.42). Subsequently, 4 patients underwent bypass surgery and 5 patients underwent major amputation. One patient died. There were 5 in-stent or edge-stent stenoses. Cox multivariate regression analysis identified TASC D lesions to be a significant risk factor for early occlusion (p = 0.035). Conclusion: TASC D lesions of femoropopliteal occlusions have poor patency rates with the use of heparin-bonded stent grafts after failed conventional angioplasty. Alternative options should be considered for these patients.

  16. Lesiones deportivas Sports injuries

    Directory of Open Access Journals (Sweden)

    Isabel Cristina Gallego Ching

    2007-04-01

    Full Text Available El estrés generado por la práctica deportiva ha originado una mayor probabilidad de que los atletas presenten lesiones agudas y crónicas. En el ámbito mundial existen diferentes investigaciones acerca de la incidencia de lesiones deportivas. La comparación de sus resultados es difícil por las diferencias en las características de la población y en la forma de reportar los datos, que varía ampliamente entre los estudios (proporciones o tasas de incidencia o tasas por cada 100 ó 1.000 participantes o tasas por horas de juego o por número de partidos jugados. Las tasas varían entre 1,7 y 53 lesiones por 1.000 horas de práctica deportiva, entre 0,8 y 90,9 por 1.000 horas de entrenamiento, entre 3,1 y 54,8 por 1.000 horas de competición y de 6,1 a 10,9 por 100 juegos. La gran variación entre las tasas de incidencia se explica por las diferencias existentes entre los deportes, los países, el nivel competitivo, las edades y la metodología empleada en los estudios. Se ha definido la lesión deportiva como la que ocurre cuando los atletas están expuestos a la práctica del deporte y se produce alteración o daño de un tejido, afectando el funcionamiento de la estructura. Los deportes de contacto generan mayor riesgo de presentar lesiones; se destacan al respecto los siguientes: fútbol, rugby, baloncesto, balonmano, artes marciales y jockey. Las lesiones ocurren con mayor probabilidad en las competencias que en el entrenamiento. Stress generated by sports practice has increased the probability that athletes suffer from acute and chronic injuries. Worldwide, there have been many different investigations concerning the incidence of sport injuries. The different ways in which results have been presented makes it difficult to compare among them. Rates of sports injuries vary between 1.7 and 53 per 1.000 hours of sports practice; 0.8 and 90.9 per 1.000 hours of training; 3.1 and 54.8 per 1.000 hours of competition, and 6.1 and 10.9 per 100

  17. Managing Carious Lesions

    DEFF Research Database (Denmark)

    Innes, N P T; Frencken, J E; Bjørndal, L

    2016-01-01

    Variation in the terminology used to describe clinical management of carious lesions has contributed to a lack of clarity in the scientific literature and beyond. In this article, the International Caries Consensus Collaboration presents 1) issues around terminology, a scoping review of current...... manifestations to the histopathology, we have based the terminology around the clinical consequences of disease (soft, leathery, firm, and hard dentine). Approaches to carious tissue removal are defined: 1)selective removal of carious tissue-includingselective removal to soft dentineandselective removal to firm...

  18. Study of genital lesions

    Directory of Open Access Journals (Sweden)

    Anand Kumar B

    2003-03-01

    Full Text Available A total of one hundred patients (75 males and 25 females age ranged from 17-65 years with genital lesions attending the STD clinic of Bowring and LC Hospitals Bangalore constituted the study group. Based on clinical features, the study groups were classified as syphilis (39, chancroid (30, herpes genitolis (13, condylomato lato (9, LGV (7t condylomata acuminata (5, genital scabies (3, granuloma inguinole (2 and genital candidiasis (1. In 68% microbiological findings confirmed the clinical diagnosis. Of the 100 cases 13% and 2% were positive for HIV antibodies and HbsAg respectively.

  19. Lesiones Deportivas En Corredores

    OpenAIRE

    Martínez Cano, Juan Pablo

    2012-01-01

    Hoy escribo como médico pero también como corredor. Por eso hay que empezar diciendo que los corredores somos unos apasionados con este deporte. Se convierte en una adicción. No se corre de vez en cuando, se hace por lo menos 5 días a la semana. Y los días que no corremos, quedamos incompletos. Eso es lo que siente un corredor, una sensación que parecería que sólo la entiende quien ha corrido. Tal vez por eso las lesiones deportivas son tan sentidas en este gremio d...

  20. The Lesion in Argentinian and Colombian Law: A Comparative Approach

    Directory of Open Access Journals (Sweden)

    Rubén S. Stiglitz

    2017-12-01

    Full Text Available The lesion intends to sanction the contractual imbalance that occurs during the stage of contract formation. The regulation of this figure should weigh the need for legal certainty in transactions with the importance of equity and contractual justice. Legal systems have chosen different positions face to this challenge, so the comparison of two legal systems such as the Colombian and the Argentine is illustrative to analyze the effectiveness of the lesion in contemporary legal business.

  1. Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages.

    Science.gov (United States)

    Lin, Hung-Chih; Lii, Chong-Kuei; Chen, Hui-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Chen, Haw-Wen

    2018-01-01

    oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent

  2. BENIGN TUMORS AND TUMOR-LIKE LESIONS OF THE PANCREAS

    Science.gov (United States)

    Basturk, Olca; Askan, Gokce

    2017-01-01

    Synopsis The pancreas is a complex organ that may give rise to large number of neoplasms and non-neoplastic lesions. This article will focus on benign neoplasms such as serous neoplasms as well as tumor-like (pseudotumoral) lesions that may be mistaken for neoplasm not only by clinicians and radiologists, but also by pathologists. The family of pancreatic pseudotumors, by a loosely defined conception of that term, includes a variety of lesions including heterotopia, hamartoma, and lipomatous pseudohypertrophy. Autoimmue pancreatitis (covered in chronic pancreatitis chapter) and paraduodenal (“groove”) pancreatitis may also lead to pseudotumor formation. Knowledge of these entities will help in making an accurate diagnosis. PMID:27926363

  3. Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by Regulating NF-κB Dependent Matrix Metalloproteinase-9 Expression via LPA2 in Macrophages

    Directory of Open Access Journals (Sweden)

    Xi Chen

    2017-04-01

    Full Text Available Lysophosphatidic acid (LPA, one of the simplest phospholipid signaling molecules, participates in formation and disruption of atherosclerotic plaque. Matrix metalloproteinases (MMPs contribute to atherosclerotic plaque rupture by involving in extracellular matrix (ECM degradation and then thinning fibrous cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated with coronary plaque instability, but the relationship between LPA and MMP-9 remains unclear. The present work therefore aimed at elucidating association between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in macrophages. We found that plasma LPA and MMP-9 levels were correlated positively (r = 0.31, P < 0.05 and both elevated significantly in patients with acute myocardial infarct (AMI. Consistent with peripheral blood levels, histochemical staining indicated that autotaxin (ATX, LPA-producing ectoenzyme, and MMP-9 were expressed frequently in the necrotic core and fibrous cap of human unstable plaques, which might increase the instability of plaque. Experiments in vitro were done with THP-1-derived macrophages and showed that LPA enhanced the expression, secretion and activity of MMP-9 in a time- and dose-dependent manner. Induction of LPA on pro-MMP-9 and active-MMP-9 was confirmed in human peripheral blood monocyte-derived macrophages. PDTC, NF-κB inhibitor, but not inhibitor of AP-1 and PPARγ, effectively prevented LPA-induced MMP-9 expression and NF-κB p65 siRNA decreased MMP-9 transcription, confirming that LPA might induce MMP-9 elevation by activating NF-κB pathway. In addition, knockdown of LPA2 attenuated LPA-induced MMP-9 expression and nucleus p65 levels. These findings revealed that LPA upregulated the expression of MMP-9 through activating NF-κB pathway in the LPA2 dependent manner, hence blocking LPA receptors signaling may provide therapeutic strategy to target plaque destabilization.

  4. Oral lesions in lupus erythematosus: correlation with cutaneous lesions.

    Science.gov (United States)

    Nico, Marcello Menta Simonsen; Vilela, Maria Apparecida Constantino; Rivitti, Evandro Ararigbóia; Lourenço, Silvia Vanessa

    2008-01-01

    Oral lesions in the context of lupus erythematosus (LE) have long been described. However, definitive agreement on about the exact nature and correct classification of these manifestations is lacking in published studies. Controversy exists on the significance of oral LE lesions regarding patient outcome. In this article, medical and dental literature on clinical and histopathological aspects of oral LE lesions are reviewed and critically discussed. A clinico-pathological correlation of oral lesions (interface mucositis-lupus mucositis) with cutaneous lesions (interface dermatitis-lupus dermatitis) is established, for those represent the mucosal counterparts of cutaneous LE. Validity about widely used but imprecise terms such as "oral ulcers", "ulcerative plaques", and others, in the context of LE, is discussed, and the uncertain relationship of these alterations to systemic disease with a worse outcome is commented. Furthermore, insights about the nature, differential diagnosis, and prognosis of oral lesions in LE patients are presented.

  5. Divergent JAM-C Expression Accelerates Monocyte-Derived Cell Exit from Atherosclerotic Plaques.

    Directory of Open Access Journals (Sweden)

    Paul F Bradfield

    Full Text Available Atherosclerosis, caused in part by monocytes in plaques, continues to be a disease that afflicts the modern world. Whilst significant steps have been made in treating this chronic inflammatory disease, questions remain on how to prevent monocyte and macrophage accumulation in atherosclerotic plaques. Junctional Adhesion Molecule C (JAM-C expressed by vascular endothelium directs monocyte transendothelial migration in a unidirectional manner leading to increased inflammation. Here we show that interfering with JAM-C allows reverse-transendothelial migration of monocyte-derived cells, opening the way back out of the inflamed environment. To study the role of JAM-C in plaque regression we used a mouse model of atherosclerosis, and tested the impact of vascular JAM-C expression levels on monocyte reverse transendothelial migration using human cells. Studies in-vitro under inflammatory conditions revealed that overexpression or gene silencing of JAM-C in human endothelium exposed to flow resulted in higher rates of monocyte reverse-transendothelial migration, similar to antibody blockade. We then transplanted atherosclerotic, plaque-containing aortic arches from hyperlipidemic ApoE-/- mice into wild-type normolipidemic recipient mice. JAM-C blockade in the recipients induced greater emigration of monocyte-derived cells and further diminished the size of atherosclerotic plaques. Our findings have shown that JAM-C forms a one-way vascular barrier for leukocyte transendothelial migration only when present at homeostatic copy numbers. We have also shown that blocking JAM-C can reduce the number of atherogenic monocytes/macrophages in plaques by emigration, providing a novel therapeutic strategy for chronic inflammatory pathologies.

  6. Atherosclerotic vessel damage in systemic lupus erythematosus and antiphospholipid syndrome in men

    Directory of Open Access Journals (Sweden)

    A. I. Iljina

    2005-01-01

    Full Text Available Objective. To study prevalence of clinical and subclinical atherosclerosis signs in men with systemic lupus erythematosus (SLE and antiphospholipid syndrome, to assess relationship between atherosclerotic vessel damage, risk factors, CRP and anti-cardiolipin antibodies (АСА Material and methods. 62 pts were included. Mean age was 35,7+11,6 years, mean disease duration - 129,3± 102 months. Traditional and related to the disease risk factors were analyzed. To reveal atherosclerotic vessel damage carotid sonographic examination was performed. Serum CRP concentration was evaluated by high sensitivity nephelometric immunoassay. IgG and IgM АСА were assessed by solid-phase immuno-enzyme assay. Results. Sonographic signs of carotid damage was revealed in 58% of pts, clinical signs of atherosclerosis - in 42%. Pts were divided into two groups according to intima-media complex thickness (IMCT. Group I included 36 pts with atherosclerotic vessel damage signs (IMCT?0,9 mm.