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  1. Electrochemical Impedance Spectroscopy to Characterize Inflammatory Atherosclerotic Plaques

    Science.gov (United States)

    Yu, Fei; Dai, Xiaohu; Beebe, Tyler; Hsiai, Tzung

    2011-01-01

    Despite advances in diagnosis and therapy, atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in the Western world. Predicting metabolically active atherosclerotic lesions has remained an unmet clinical need. We hereby developed an electrochemical strategy to characterize the inflammatory states of high-risk atherosclerotic plaques. Using the concentric bipolar microelectrodes, we sought to demonstrate distinct Electrochemical Impedance Spectroscopic (EIS) measurements for unstable atherosclerotic plaques that harbored active lipids and inflammatory cells. Using equivalent circuits to simulate vessel impedance at the electrode-endoluminal tissue interface, we demonstrated specific electric elements to model working and counter electrode interfaces as well as the tissue impedance. Using explants of human coronary, carotid, and femoral arteries at various Stary stages of atherosclerotic lesions (n = 15), we performed endoluminal EIS measurements (n = 147) and validated with histology and immunohistochemistry. We computed the vascular tissue resistance using the equivalent circuit model and normalized the resistance to the lesion-free regions. Tissue resistance was significantly elevated in the oxLDL-rich thin-cap atheromas (1.57±0.40, n = 14, p 0.05). Hence, we demonstrate that the application of EIS strategy was sensitive to detect fibrous cap oxLDL-rich lesions and specific to distinguish oxLDL-absent fibroatheroma. PMID:21959227

  2. A diet rich in conjugated linoleic acid and butter increases lipid peroxidation but does not affect atherosclerotic, inflammatory, or diabetic risk markers in healthy young men

    DEFF Research Database (Denmark)

    Raff, Marianne; Tholstrup, Tine; Basu, Samar;

    2008-01-01

    Intake of conjugated linoleic acid (CLA) has been demonstrated to beneficially affect risk markers of atherosclerosis and diabetes in rats. CLA is naturally found in milk fat, especially from cows fed a diet high in oleic acid, and increased CLA intake can occur concomitantly with increased milk...... fat intake. Our objective was to investigate the effect of CLA as part of a diet rich in butter as a source of milk fat on risk markers of atherosclerosis, inflammation, diabetes type 11, and lipid peroxidation. A total of 38 healthy young men were given a diet with 115g/d of CLA-rich fat (5.5 g/d CLA...... esters, and phospholipids reflected that of the intervention diets. The CLA diet resulted in increased lipid peroxidation measured as an 83% higher 8-iso-prostaglandin F-2 alpha concentration compared with the control, P...

  3. Atherosclerotic cardiovascular disease in patients with chronic inflammatory joint disorders.

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    Agca, R; Heslinga, S C; van Halm, V P; Nurmohamed, M T

    2016-05-15

    Inflammatory joint disorders (IJD), including rheumatoid arthritis (RA), ankylosing spondylitis (ASp) and psoriatic arthritis (PsA), are prevalent conditions worldwide with a considerable burden on healthcare systems. IJD are associated with increased cardiovascular (CV) disease-related morbidity and mortality. In this review, we present an overview of the literature. Standardised mortality ratios are increased in IJD compared with the general population, that is, RA 1.3-2.3, ASp 1.6-1.9 and PsA 0.8-1.6. This premature mortality is mainly caused by atherosclerotic events. In RA, this CV risk is comparable to that in type 2 diabetes. Traditional CV risk factors are more often present and partially a consequence of changes in physical function related to the underlying IJD. Also, chronic systemic inflammation itself is an independent CV risk factor. Optimal control of disease activity with conventional synthetic, targeted synthetic and biological disease-modifying antirheumatic drugs decreases this excess risk. High-grade inflammation as well as anti-inflammatory treatment alter traditional CV risk factors, such as lipids. In view of the above-mentioned CV burden in patients with IJD, CV risk management is necessary. Presently, this CV risk management is still lacking in usual care. Patients, general practitioners, cardiologists, internists and rheumatologists need to be aware of the substantially increased CV risk in IJD and should make a combined effort to timely initiate CV risk management in accordance with prevailing guidelines together with optimal control of rheumatic disease activity. CV screening and treatment strategies need to be implemented in usual care. PMID:26888573

  4. Irradiation of existing atherosclerotic lesions increased inflammation by favoring pro-inflammatory macrophages

    International Nuclear Information System (INIS)

    Background and purpose: Recent studies have shown an increased incidence of localized atherosclerosis and subsequent cardiovascular events in cancer patients treated with thoracic radiotherapy. We previously demonstrated that irradiation accelerated the development of atherosclerosis and predisposed to an inflammatory plaque phenotype in young hypercholesterolemic ApoE−/− mice. However, as older cancer patients already have early or advanced stages of atherosclerosis at the time of radiotherapy, we investigated the effects of irradiation on the progression of existing atherosclerotic lesions in vivo. Material and methods: ApoE−/− mice (28 weeks old) received local irradiation with 14 or 0 Gy (sham-treated) at the aortic arch and were examined after 4 and 12 weeks for atherosclerotic lesions, plaque size and phenotype. Moreover, we investigated the impact of irradiation on macrophage phenotype (pro- or anti-inflammatory) and function (efferocytotic capacity, i.e. clearance of apoptotic cells) in vitro. Results: Irradiation of existing lesions in the aortic arch resulted in smaller, macrophage-rich plaques with intraplaque hemorrhage and increased apoptosis. In keeping with the latter, in vitro studies revealed augmented polarization toward pro-inflammatory macrophages after irradiation and reduced efferocytosis by anti-inflammatory macrophages. In addition, considerably more lesions in irradiated mice were enriched in pro-inflammatory macrophages. Conclusions: Irradiation of existing atherosclerotic lesions led to smaller but more inflamed plaques, with increased numbers of apoptotic cells, most likely due to a shift toward pro-inflammatory macrophages in the plaque

  5. Effect of rosuvastatin on inflammatory factors and carotid atherosclerotic plaque in patients with acute ischemic stroke

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    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.

  6. Regulation of microRNA-155 in atherosclerotic inflammatory responses by targeting MAP3K10.

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    Jianhua Zhu

    Full Text Available AIMS: Accumulating evidence suggest that numerous microRNAs (miRNAs play important roles in cell proliferation, apoptosis, and differentiation, as well as various diseases that accompany inflammatory responses. Inflammation is known to be a major contributor to atherogenesis. Previous studies provide promising evidence in support of the role of miRNAs in cardiovascular disease. However, mechanistic data on these small molecules in atherosclerosis (AS are still missing. The present study aims to investigate the potential role of miRNAs in AS. METHODS AND RESULTS: The miRNA transcriptase was verified by TaqMan real-time polymerase chain reaction assay. Thoracic aorta samples were obtained from Apolipoprotein E knockout mice, and plasma samples were from coronary artery disease (CAD patients. The results showed that the miR-155 level was the most significantly elevated both in AS mice and CAD patients relative to the normal control. The functional role of miR-155 in the atherosclerotic path physiological process was also observed in vivo and in vitro. The observations suggested that miR-155 is a part of a negative feedback loop, which down-modulates inflammatory cytokine production and decreases AS progression. miR-155 was also found to mediate the inflammatory response and mitogen-activated protein kinase (MAPK pathway by targeting mitogen-activated protein kinase kinase kinase 10. CONCLUSIONS: miR-155 contributes to the prevention of AS development and progression. It may also be involved in the posttranscriptional regulation of the inflammatory response and MAPK pathway by targeting mitogen-activated protein kinase kinase kinase 10.

  7. Psychological stress increases expression of aortic plaque intercellular adhesion molecule-1 and serum inflammatory cytokines in atherosclerotic rabbit model

    Institute of Scientific and Technical Information of China (English)

    Muwei Li; Xianpei Wang; Lei Yang; Chuanyu Gao; Yexin Ma

    2008-01-01

    Plaque rupture,platelet aggregation,and thrombogenesis are the main mechanisms of acute coronary syndrome (ACS),and inflammation factors play key roles in plaque unstability.Psychological stress promotes acute inflammatory response,leading to increased circulating levels of C-reactive protein (CRP),IL-6,and serum intercellular adhesion molecule (sICAM)-1.But it is not clear that whether psychological stress has a direct effect on atherosclerotic plaque stability.The purpose of this study was to investigate effects of chronic psychological stress on inflammatory marker (ICAM-1 ) in atherosclerotic plaque,and inflammatory markers in peripheral blood.Materials and methods Sixty male rabbits were randomized into 2 groups:the control group (n =10) and the atherosclerotic group (n =50).The latter were fed on high fatty diet and were given a large dose of vitamin D3 (3 600 000IU/kg) via intraperitoneal injection.After 8 weeks,the atherosclerotic model was estaslished.Then the 50 atherosclerotic model rabbits were divided into 3 subgroups:no-stress subgroup (n = 16),physiological stress subgroup (n = 16) and psychological stress subgroup (n =18).In physiological stress subgroup and psychological stress subgroup,drinking was cut from twice a day to once a day.At the same time,psychological stress subgroup was given empty bottle stress,and this process lasted for 2 weeks.One hour after the last stress,the blood samples were collected and the serum levels of CRP,IL-6 amd ICAM-1 were tested by radioimmunoassay or enzyme linked immunosorbent assay.The aorta and heart were extracted for pathology examination,and the express of ICAM-1 was tested by immunohistochemical examination.Results (1) After effective atherosclerotic animal model construction,the expression of ICAM-1 in aorta was higher in atherosclerotic group than that in control group (P<0.01),and was notably higher in psychological stress subgroup than that in no-stress subgroup or in physiological stress subgroup (2

  8. Hematopoietic Fas deficiency does not affect experimental atherosclerotic lesion formation despite inducing a proatherogenic state.

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    de Claro, R Angelo; Zhu, Xiaodong; Tang, Jingjing; Morgan-Stevenson, Vicki; Schwartz, Barbara R; Iwata, Akiko; Liles, W Conrad; Raines, Elaine W; Harlan, John M

    2011-06-01

    The Fas death receptor (CD95) is expressed on macrophages, smooth muscle cells, and T cells within atherosclerotic lesions. Given the dual roles of Fas in both apoptotic and nonapoptotic signaling, the aim of the present study was to test the effect of hematopoietic Fas deficiency on experimental atherosclerosis in low-density lipoprotein receptor-null mice (Ldlr(-/-)). Bone marrow from Fas(-/-) mice was used to reconstitute irradiated Ldlr(-/-) mice as a model for atherosclerosis. After 16 weeks on an 0.5% cholesterol diet, no differences were noted in brachiocephalic artery lesion size, cellularity, or vessel wall apoptosis. However, Ldlr(-/-) mice reconstituted with Fas(-/-) hematopoietic cells had elevated hyperlipidemia [80% increase, relative to wild-type (WT) controls; P < 0.001] and showed marked elevation of plasma levels of CXCL1/KC, CCL2/MCP-1, IL-6, IL-10, IL-12 subunit p70, and soluble Fas ligand (P < 0.01), as well as systemic microvascular inflammation. It was not possible to assess later stages of atherosclerosis because of increased mortality in Fas(-/-) bone marrow recipients. Our data indicate that hematopoietic Fas deficiency does not affect early atherosclerotic lesion development in Ldlr(-/-) mice.

  9. 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.

  10. [Inflammatory-destructive biomarkers of atherosclerotic plaques instability. Study of arterial wall and blood].

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    Ragino, Iu I; Cherniavskiĭ, A M; Polonskaia, Ia V; Volkov, A M; Kashtanova, E V; Tsymbal, S Iu; Polovnikova, E M

    2012-01-01

    Concentrations of tumor necrosis factor, interleukin 1- and its receptor antagonist, IL-6, IL-8, IL-18, IL-2, ligand of CD40 receptor (CD40L), high sensitive C-reactive protein (hsCRP), monocyte chemotactic protein -1, endothelial monocyte activating protein II, adhesive molecules (sICAM-1 and sVCAM-1), matrix metalloproteinase (MMP-3, MMP-7, MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) and endothelin-1 were studied in blood and in coronary artery intima/media of men with coronary atherosclerosis without acute coronary syndrome. Blood levels of hsCRP, IL-8, IL-6 and CD40L were higher, while blood levels of sVCAM and TIMP-1 were lower in men with prevalence of unstable atherosclerotic plaques compared to men with prevalence of stable atherosclerotic plaques in coronary arteries. Blood levels of hsCRP, IL-6 and IL-8 correlated with characteristics of coronary artery atherosclerotic plaques instability. Correlation between hsCRP blood level and hsCRP concentration in coronary artery intima/media material was also revealed. PMID:22839584

  11. Glyoxalase 1 overexpression does not affect atherosclerotic lesion size and severity in ApoE-/- mice with or without diabetes

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    Hanssen, Nordin M J; Brouwers, Olaf; Gijbels, Marion J;

    2014-01-01

    E(-/-) huGLO1(+/-) (n = 20) mice. To induce diabetes, we injected a subset with streptozotocin (STZ) to generate diabetic ApoE(-/-) (n = 8) and ApoE(-/-) huGLO1(+/-) (n = 13) mice. All mice were fed chow and sacrificed at 25 weeks of age. The GLO1 activity was three-fold increased in huGLO1(+/-) aorta, but......(+/-) overexpression. Although diabetic mice showed decreased GLO1 expression (P < 0.05) and increased lesion size (P < 0.05) in comparison with non-diabetic mice, GLO1 overexpression also did not affect the aortic root lesion size or inflammation in diabetic mice. CONCLUSION: In ApoE(-/-) mice with or without...... diabetes, GLO1 overexpression did not lead to decreased atherosclerotic lesion size or systemic inflammation. Increasing GLO1 levels does not seem to be an effective strategy to reduce glycation in atherosclerotic lesions, likely due to increased AGE formation through GLO1-independent mechanisms....

  12. Regulation of MicroRNA-155 in Atherosclerotic Inflammatory Responses by Targeting MAP3K10

    OpenAIRE

    Zhu, Jianhua; Chen, Ting; Yang, Lin; Li, Zhoubin; Wong, Mei Mei; Zheng, Xiaoye; Pan, Xiaoping; Zhang, Li; Yan, Hui

    2012-01-01

    Aims Accumulating evidence suggest that numerous microRNAs (miRNAs) play important roles in cell proliferation, apoptosis, and differentiation, as well as various diseases that accompany inflammatory responses. Inflammation is known to be a major contributor to atherogenesis. Previous studies provide promising evidence in support of the role of miRNAs in cardiovascular disease. However, mechanistic data on these small molecules in atherosclerosis (AS) are still missing. The present study aims...

  13. An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques

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    Fredman, Gabrielle; Hellmann, Jason; Proto, Jonathan D.; Kuriakose, George; Colas, Romain A.; Dorweiler, Bernhard; Connolly, E. Sander; Solomon, Robert; Jones, David M.; Heyer, Eric J.; Spite, Matthew; Tabas, Ira

    2016-01-01

    Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB4), are significantly decreased in the vulnerable regions. SPMs are also decreased in advanced plaques of fat-fed Ldlr−/− mice. Administration of RvD1 to these mice during plaque progression restores the RvD1:LTB4 ratio to that of less advanced lesions and promotes plaque stability, including decreased lesional oxidative stress and necrosis, improved lesional efferocytosis, and thicker fibrous caps. These findings provide molecular support for the concept that defective inflammation resolution contributes to the formation of clinically dangerous plaques and offer a mechanistic rationale for SPM therapy to promote plaque stability. PMID:27659679

  14. 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.

  15. Inflammatory abdominal aortic aneurysm:clinical features and long term outcome in comparison with atherosclerotic abdominal aortic aneurysm

    Institute of Scientific and Technical Information of China (English)

    YIN Ming-di; ZHANG Jian; WANG Shao-ye; DUAN Zhi-quan; XIN Shi-jie

    2010-01-01

    Background Inflammatory abdominal aortic aneurysms (IAAAs) are rare but distinct clinical entities of atherosclerotic abdominal aortic aneurysms (aAAAs).In this study we report a 20-year single institution experience for IAAA and analyze their clinical features and long term outcome in comparison with aAAA.Methods Between 1988 and 2008, 412 cases of abdominal aortic aneurysms (AAAs) underwent elective surgical operations, 11 (2.7%) of whom were diagnosed as IAAAs and 389 (94.4%) were diagnosed as aAAAs.The former group was matched in a case control fashion to a group of 33 patients with aAAAs having similar characteristics of age, gender, and preoperative risk factors.All available clinical, pathologic, and postoperative variables were retrospectively reviewed, and the two groups were compared.Results The two groups did not differ significantly in clinical characteristics and preoperative risk factors, although patients with IAAAs were significantly more symptomatic (100% vs.42.4%, P=0.001) and had larger aneurysms on admission ((7.4±0.7) cm vs.(6.3±0.9) cm, P=0.006).In IAAAs, the preoperative erythrocyte sedimentation rate was found to be significantly elevated compared to aAAA group ((44.5±9.1) mm/h vs.(11.4±5.4) mm/h, P <0.05).Surgical morbidity and mortality rates did not differ between the two groups.The operation time for patients with IAAAs was significantly longer than that for patients with aAAAs ((308±36) minutes vs.(224±46) minutes, P <0.05), but the cross-clamp time was similar in both groups ((41.5±6.2) minutes vs.(41.8±6.2) minutes, P=0.92).A five-year survival rate analysis showed no significant difference between the two groups (P=0.711).Conclusions Despite having more symptoms, larger size and longer operation time, patients with IAAA can now be treated with approaches that cause Iow morbidity and mortality, similar to patients with aAAA.Long term outcome of IAAA patients is of no difference from aAAA patients.

  16. Dietary supplementation with Cyperus esculentus L (tiger nut tubers attenuated atherosclerotic lesion in apolipoprotein E knockout mouse associated with inhibition of inflammatory cell responses

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    Mohamed L.  Salem

    2005-01-01

    Full Text Available Atherosclerosis is a pathological process, where recruitment of mononuclear cells results in the growth of fibro-fatty plaques. Apolipoprotein E (ApoE is a legend for the uptake of lipoproteins, and deficiency of ApoE leads to the accumulation of low-density lipoprotein. Utilizing ApoE-/- mouse, which spontaneously develop atherosclerosis on low-fat chow diets, the present study showed that feeding these mice on a diet supplemented with the whole tubers of Cyperus esculentus L (tiger nut resulted in attenuation of the development of atherosclerotic lesions. The anti-atherosclerotic effect was associated with a decrease in the number of monocytes, macrophages and dendritic cells in blood, and the expression of IL-2Rαand LFA-1 by these cells. Further, in vitro proliferation of blood and spleen cells from tiger nut-fed ApoE-/- mice showed lower proliferation in responses to ConA and LPS, a T and B cell mitogen, respectively. Further, in vitro treatment of blood and spleen cells with water or ethanol extracts of tiger nut markedly increased their proliferation in response to ConA. Collectively, these data indicate that ingredients of tiger nut tubers exhibit anti-inflammatory properties upon inflammation, and immunostimulatory effects in immunocompetent hosts.

  17. Impact of different ratios of Omega-6 polyundaturated fatty acids to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) on atherosclerotic lesion formation and inflammatory factors in the LDL receptor knockout mouse

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    The objective was to assess the effect of different ratios of omega-6 to EPA plus DHA on atherosclerotic lesion formation and plasma inflammatory markers in LDLr-/- mice. Mice (n=10/group) were fed the following diets for 32 weeks: high fat (20% w/w) without EPA and DHA (HF omega-6), and high fat wi...

  18. Cathecins in ethanolic extracts of Garcinia mangostana fruit pericarp and anti-inflammatory effect in atherosclerotic rats

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    Rochmad Romdoni

    2013-04-01

    Full Text Available Objective: The present study was aimed to determine whether the ethanolic extract of Garcinia mangostana (mangosteen fruit pericarp (EEMP changes several markers of inflammation, such as nuclear factor kappaB (NF-κB p65/p50 distribution, tumor necrosis factor (TNF-α levels, and nitric oxide (NO in the atherosclerotic rats model. Methods: Thirty male Wistar rats were divided into five groups (n = 6 each, including standard diet (control group, hypercholesterolemic diet (HD group, HD + EEMP at dose of 200, 400 and 800 mg/kg body weight (BW. Analysis of NF-κB p65/p50 distribution was done by imunnohistochemistry method. The levels of TNF-α and NO were measured by ELISA. Results: High cholesterol diet significantly increased NF-κB p65/p50 distribution, TNF-α levels and NO levels compared with control group. The levels of NF-κB p65/p50 distribution was significantly decreased in EEGM-treated group at doses 200 and 800 mg/kg BW than that in atherosclerosis group. The levels of NO and TNF-α were significantly decreased in EEGM-treated group at all doses compared to atherosclerosis group, but did not reach levels at standard diet. Conclusions: The present data suggests that EEMP inhibits inflammation in atherosclerotic rats due to inhibition of distribution NF-κB p65/p50 into the nucleus and decreases TNF-α and NO levels. [J Exp Integr Med 2013; 3(2.000: 137-140

  19. Decreased Regulatory T Cells in Vulnerable Atherosclerotic Lesions: Imbalance between Pro- and Anti-Inflammatory Cells in Atherosclerosis

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    Ilonka Rohm

    2015-01-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease of the arterial wall in which presentation of autoantigens by dendritic cells (DCs leads to the activation of T cells. Anti-inflammatory cells like Tregs counterbalance inflammation in atherogenesis. In our study, human carotid plaque specimens were classified as stable (14 and unstable (15 according to established morphological criteria. Vessel specimens (n=12 without any signs of atherosclerosis were used as controls. Immunohistochemical staining was performed to detect different types of DCs (S100, fascin, CD83, CD209, CD304, and CD123, proinflammatory T cells (CD3, CD4, CD8, and CD161, and anti-inflammatory Tregs (FoxP3. The following results were observed: in unstable lesions, significantly higher numbers of proinflammatory cells like DCs, T helper cells, cytotoxic T cells, and natural killer cells were detected compared to stable plaques. Additionally, there was a significantly higher expression of HLA-DR and more T cell activation (CD25, CD69 in unstable lesions. On the contrary, unstable lesions contained significantly lower numbers of Tregs. Furthermore, a significant inverse correlation between myeloid DCs and Tregs was shown. These data suggest an increased inflammatory state in vulnerable plaques resulting from an imbalance of the frequency of local pro- and anti-inflammatory immune cells.

  20. Atherosclerotic inflammatory reaction and microRNA%动脉粥样硬化炎症反应与microRNA

    Institute of Scientific and Technical Information of China (English)

    梁鑫

    2013-01-01

    动脉粥样硬化是一种慢性动脉炎症反应性疾病,其病因至今尚未完全阐明.microRNA参与调控动脉粥样硬化发生、发展过程中各个环节的炎性细胞的发育、分化及其功能的执行,对microRNA参与调控这些细胞的机制进行深入研究将有可能阐明microRNA在动脉粥样硬化发病过程中的意义和作用.%Atherosclerosis is a chronic inflammatory artery disease,its pathogensis has not been completely demonstrated.MicroRNA modulates ontogenesis,differentiation and functional performance of inflammatory cells in every stage of atherosclerosis.Therefore,it is helpful for illustrating the significance and effects of microRNA in those inflammatory cells and the depth researches would be carried out the functions and mechanisms of microRNAs in atherosclerosis.

  1. Expression of pro-inflammatory and anti-inflammatory cytokines in brain of atherosclerotic rats and effects of Ginkgo biloba extract

    Institute of Scientific and Technical Information of China (English)

    Ya-bin JIAO; Yao-cheng RUI; Tie-jun LI; Peng-yuan YANG; Yan QIU

    2005-01-01

    Aim: To study the protein and mRNA expressions of pro-inflammatory and antiinflammatory cytokines in the brain of rats with atherosclerosis (AS) and the effects of Ginkgo biloba extract (GbE) on expressions of cytokines.Methods:The experimental model of AS in rats were established by intraperitioneal injection of vitamin D3 with high fat/cholesterol diet.GbE 100 mg/kg was administered to rats by ig.After 8 weeks, the expressions of IL- 1β, TNF-α, IL-10, and IL-10R in the brain tissues of AS rats were detected by enzyme-linked immunosorbant assay,immunohistochemistry, Western blotting, and reverse transcriptase polymerase chain reaction.Results: The protein and mRNA expressions of IL-1 β, TNF-α, and IL-10 in the brains were markedly higher in AS groups than that in control groups (6.11±0.15, 1.55±0.14, 0.54±0.04 ng/g wet weight vs 0.80±0.14, 0.33±0.09, and 0.33±0.02 ng/g wet weight, respectively).The protein and mRNA expressions of IL-1β and TNF-α in the brains were markedly lower in GbE groups (3.82±0.54, 0.95±0.08 ng/g wet weight) than that in AS groups, the protein and mRNA expressions of IL-10 and IL-10R in the brains were markedly higher in GbE groups (0.85±0.06 ng/g wet weight) than that in AS groups.Conclusion: GbE inhibited production of pro-inflammatory cytokines IL-1 β and TNF-α, but upregulated the production of anti-inflammatory cytokines, IL-10 and IL-1 0R in brain,which might be related with its anti-AS actions.

  2. Affective and inflammatory responses among orchestra musicians in performance situation.

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    Pilger, Alexander; Haslacher, Helmuth; Ponocny-Seliger, Elisabeth; Perkmann, Thomas; Böhm, Karl; Budinsky, Alexandra; Girard, Angelika; Klien, Katharina; Jordakieva, Galateja; Pezawas, Lukas; Wagner, Oswald; Godnic-Cvar, Jasminka; Winker, Robert

    2014-03-01

    A number of studies have shown that mental challenge under controlled experimental conditions is associated with elevations in inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). However, relatively little work has been done on the effects of 'naturalistic' stressors on acute changes in inflammatory markers. The present study examined whether perceived arousal, valence and dominance in musicians are associated with pro-inflammatory and oxidative responses to a concert situation. Blood and salivary samples obtained from 48 members of a symphony orchestra on the day of rehearsal (i.e., control situation) and on the following day of premiere concert (i.e., test situation) were used to determine changes in salivary cortisol, pro-inflammatory markers (plasma myeloperoxidase, serum CRP, plasma IL-6), oxidative stress markers (paraoxonase1 activity and malondialdehyde), and homocysteine, a risk factor for vascular disease. Results of regression analyses showed a significant trend to increased myeloperoxidase (MPO) response in individuals with low valence score. Both affective states, valence and arousal, were identified as significant predictors of cortisol response during concert. In addition, control levels of plasma malondialdehyde were positively correlated with differences in IL-6 levels between premiere and rehearsal (r=.38, p=.012), pointing to higher oxidative stress in individuals with pronounced IL-6 response. Our results indicate that stress of public performance leads to increased concentrations of plasma MPO (20%), IL-6 (27%) and salivary cortisol (44%) in musicians. The decreasing effect of pleasantness on the MPO response was highly pronounced in non-smokers (r=-.60, p<.001), suggesting a significant role of emotional valence in stress-induced secretion of MPO. Additional studies are needed to assess the generalizability of these findings to other 'naturalistic' stress situations.

  3. Affected by Inflammatory Diseases: Diagnostic and Pathogenetic Insights

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    Alessandra Pontillo

    2011-01-01

    Full Text Available Human glycolytic enzyme α-enolase was associated with human diseases and with inflammation. An ELISA test was developed to measure anti-α-enolase AAE IgG and AAE IgA in the serum from patients affected by inflammatory diseases with the purpose to evaluate it as a novel diagnostic marker. 80 healthy blood donors and 194 paediatric patients affected by Juvenile idiopathic arthritis (JIA, celiac disease (CD, Crohn's Disease (CrD, hereditary periodic fever (HPF, and PFAPA syndrome were included in the study. HPF patients showed high levels of AAE antibodies, whereas JIA, CD, and CrD presented only partial results. Benign fevers such as PFAPA were almost negative for AAE Abs. These findings suggested that the genetic dysfunction of inflammasome associated with HPF could lead to the formation of AAE Abs that could be used for an early and easy diagnosis.

  4. Intracranial Atherosclerotic Disease

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    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.

  5. Gr-1⁺CD11b⁺ immature myeloid cells (IMC) promote resistance of pro-inflammatory T cells to suppression by regulatory T cells in atherosclerotic Apo E- deficient mice.

    Science.gov (United States)

    Chen, Yulin; Jian, Ying; Liu, Minjie; Zhong, Liang; Zhang, Fang; Yang, Weifeng; Xu, Zhao; Chen, Guofan; Liu, Yuhua

    2014-01-01

    Accumulating evidence indicates that both defects in Treg numbers and/or function as well as resistance of effector T cells to suppression may contribute to the development of human chronic inflammatory diseases. However, which mechanism involved in the progression of atherosclerosis remains unclear. In this study, we evaluated the production and function of CD4⁺ inflammatory and regulatory T cells in atherosclerosis-prone mice. We found that the hyperactivity and unresponsiveness to Treg-mediated suppression of inflammatory CD4⁺ T cells occurred in the progression of atherosclerosis, though Treg cells were present in very large numbers and fully functional. We further found that Gr-1⁺CD11b⁺ immature myeloid cells were significantly accumulated in atherosclerotic Apo E⁻/⁻ mice, and they promoted resistance of inflammatory CD4⁺ T cells to Treg-mediated suppression in vitro and in vivo. we further confirmed that Gr-1⁺CD11b⁺ immature myeloid cells produced high level of interleukin 6 which was at least partially responsible for inducing unresponsiveness of inflammatory CD4⁺ T cells to suppression via activation of Jak/Stat signaling pathway. Taken together, these findings might provide new insights to explore potential targets for immune therapeutic intervention in atherosclerosis.

  6. 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 wh

  7. Nuclear Molecular Imaging for Vulnerable Atherosclerotic Plaques

    OpenAIRE

    Lee, Soo Jin; Paeng, Jin Chul

    2015-01-01

    Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell...

  8. Sleep deprivation affects inflammatory marker expression in adipose tissue

    Directory of Open Access Journals (Sweden)

    Santos Ronaldo VT

    2010-10-01

    Full Text Available Abstract Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation. Methods The study consisted of two groups: a control (C group and a paradoxical sleep deprivation by 96 h (PSD group. Ten rats were randomly assigned to either the control group (C or the PSD. Mesenteric (MEAT and retroperitoneal (RPAT adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL-6, interleukin (IL-10 and tumour necrosis factor (TNF-α were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum. Results IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-α levels decreased in MEAT. Glucose, triglycerides (TG, VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased. Conclusion PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-α protein concentrations in MEAT and increased levels of corticosterone in serum.

  9. The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE(-/-) mice

    DEFF Research Database (Denmark)

    Kim, Christine H. J.; Mitchell, James B.; Bursill, Christina A.;

    2015-01-01

    cholesterol, inflammatory cytokines and markers (interleukin-6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase, MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells. RESULTS: High...... fat feeding resulted in marked increases in body mass and plasma lipid levels. Dietary TEMPOL decreased both parameters. In the high-fat-fed mice significant elevations in plasma lipid levels and the inflammatory markers IL-6, MCP-1, MPO, SAA were detected, along with an increase in leptin...

  10. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models

    NARCIS (Netherlands)

    Kleemann, R.; Verschuren, L.; Morrison, M.; Zadelaar, A.S.M.; Erk, M.J. van; Wielinga, P.Y.; Kooistra, T.

    2011-01-01

    Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein

  11. Positive affect and health-related neuroendocrine, cardiovascular, and inflammatory processes

    OpenAIRE

    Steptoe, A; Wardle, J; Marmot, M.

    2005-01-01

    Negative affective states such as depression are associated with premature mortality and increased risk of coronary heart disease, type 2 diabetes, and disability. It has been suggested that positive affective states are protective, but the pathways through which such effects might be mediated are poorly understood. Here we show that positive affect in middle-aged men and women is associated with reduced neuroendocrine, inflammatory, and cardiovascular activity. Positive affect was assessed b...

  12. 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.

  13. Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.

    Science.gov (United States)

    Yang, Wei; Ng, Fu Liang; Chan, Kenneth; Pu, Xiangyuan; Poston, Robin N; Ren, Meixia; An, Weiwei; Zhang, Ruoxin; Wu, Jingchun; Yan, Shunying; Situ, Haiteng; He, Xinjie; Chen, Yequn; Tan, Xuerui; Xiao, Qingzhong; Tucker, Arthur T; Caulfield, Mark J; Ye, Shu

    2016-07-01

    Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD

  14. Paclitaxel-Coated Balloons: Investigation of Drug Transfer in Healthy and Atherosclerotic Arteries – First Experimental Results in Rabbits at Low Inflation Pressure

    OpenAIRE

    Stolzenburg, Nicola; Breinl, Janni; Bienek, Stephanie; Jaguszewski, Milosz; Löchel, Melanie; Taupitz, Matthias; Speck, Ulrich; Wagner, Susanne; Schnorr, Jörg

    2016-01-01

    Purpose Beyond antiproliferative properties, paclitaxel exhibits anti-inflammatory activity, which might be beneficial in the local treatment of nonocclusive coronary artery disease. Paclitaxel release and tissue concentrations after paclitaxel-coated balloon treatment using different pressures have not been investigated so far. The aim of the study was to investigate in an atherosclerotic rabbit model whether drug transfer from paclitaxel-coated balloons into the vessel wall is affected by t...

  15. Chemokine Receptor 7 Knockout Attenuates Atherosclerotic Plaque Development

    NARCIS (Netherlands)

    Luchtefeld, Maren; Grothusen, Christina; Gagalick, Andreas; Jagavelu, Kumaravelu; Schuett, Harald; Tietge, Uwe J. F.; Pabst, Oliver; Grote, Karsten; Drexler, Helmut; Foerster, Reinhold; Schieffer, Bernhard

    2010-01-01

    Background-Atherosclerosis is a systemic inflammatory disease characterized by the formation of atherosclerotic plaques. Both innate immunity and adaptive immunity contribute to atherogenesis, but the mode of interaction is poorly understood. Chemokine receptor 7 (CCR7) is critically involved in the

  16. Food, nutrients and nutraceuticals affecting the course of inflammatory bowel disease.

    Science.gov (United States)

    Uranga, José Antonio; López-Miranda, Visitación; Lombó, Felipe; Abalo, Raquel

    2016-08-01

    Inflammatory bowel diseases (ulcerative colitis; Crohn's disease) are debilitating relapsing inflammatory disorders affecting the gastrointestinal tract, with deleterious effect on quality of life, and increasing incidence and prevalence. Mucosal inflammation, due to altered microbiota, increased intestinal permeability and immune system dysfunction underlies the symptoms and may be caused in susceptible individuals by different factors (or a combination of them), including dietary habits and components. In this review we describe the influence of the Western diet, obesity, and different nutraceuticals/functional foods (bioactive peptides, phytochemicals, omega 3-polyunsaturated fatty acids, vitamin D, probiotics and prebiotics) on the course of IBD, and provide some hints that could be useful for nutritional guidance. Hopefully, research will soon offer enough reliable data to slow down the spread of the disease and to make diet a cornerstone in IBD therapy. PMID:27267792

  17. Efficacy of risedronate in a post-menopausal woman affected by osteoporosis and inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Stefano Palomba

    2010-06-01

    Full Text Available Post-menopausal osteoporosis is a skeletal disease that can be asymptomatic and is sometimes underdiagnosed and undertreated. Post-menopausal osteoporosis can be associated with fractures and consequent impaired quality of life and increase of health care costs. Bisphosphonates are a therapeutic choice, because they proved to be effective in preventing bone loss. The current case report shows the efficacy of six-month risedronate administration in a post-menopausal woman affected by osteoporosis and inflammatory bowel disease in reducing biochemical bone turnover markers and increasing bone mineral density.

  18. Positive affect and health-related neuroendocrine, cardiovascular, and inflammatory processes.

    Science.gov (United States)

    Steptoe, Andrew; Wardle, Jane; Marmot, Michael

    2005-05-01

    Negative affective states such as depression are associated with premature mortality and increased risk of coronary heart disease, type 2 diabetes, and disability. It has been suggested that positive affective states are protective, but the pathways through which such effects might be mediated are poorly understood. Here we show that positive affect in middle-aged men and women is associated with reduced neuroendocrine, inflammatory, and cardiovascular activity. Positive affect was assessed by aggregating momentary experience samples of happiness over a working day and was inversely related to cortisol output over the day, independently of age, gender, socioeconomic position, body mass, and smoking. Similar patterns were observed on a leisure day. Happiness was also inversely related to heart rate assessed by using ambulatory monitoring methods over the day. Participants underwent mental stress testing in the laboratory, where plasma fibrinogen stress responses were smaller in happier individuals. These effects were independent of psychological distress, supporting the notion that positive well-being is directly related to health-relevant biological processes. PMID:15840727

  19. Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence.

    Science.gov (United States)

    Bilski, Jan; Mazur-Bialy, Agnieszka; Brzozowski, Bartosz; Magierowski, Marcin; Zahradnik-Bilska, Janina; Wójcik, Dagmara; Magierowska, Katarzyna; Kwiecien, Slawomir; Mach, Tomasz; Brzozowski, Tomasz

    2016-08-01

    The inflammatory bowel disease (IBD) consisting of Crohn's disease (CD) and ulcerative colitis (UC) are defined as idiopathic, chronic and relapsing intestinal disorders occurring in genetically predisposed individuals exposed to environmental risk factors such as diet and microbiome changes. Since conventional drug therapy is expensive and not fully efficient, there is a need for alternative remedies that can improve the outcome in patients suffering from IBD. Whether exercise, which has been proposed as adjunct therapy in IBD, can be beneficial in patients with IBD remains an intriguing question. In this review, we provide an overview of the effects of exercise on human IBD and experimental colitis in animal models that mimic human disease, although the information on exercise in human IBD are sparse and poorly understood. Moderate exercise can exert a beneficial ameliorating effect on IBD and improve the healing of experimental animal colitis due to the activity of protective myokines such as irisin released from working skeletal muscles. CD patients with higher levels of exercise were significantly less likely to develop active disease at six months. Moreover, voluntary exercise has been shown to exert a positive effect on IBD patients' mood, weight maintenance and osteoporosis. On the other hand, depending on its intensity and duration, exercise can evoke transient mild systemic inflammation and enhances pro-inflammatory cytokine release, thereby exacerbating the gastrointestinal symptoms. We discuss recent advances in the mechanism of voluntary and strenuous exercise affecting the outcome of IBD in patients and experimental animal models. PMID:27255494

  20. Autophagy gene polymorphism is associated with susceptibility to leprosy by affecting inflammatory cytokines.

    Science.gov (United States)

    Yang, Degang; Chen, Jia; Shi, Chao; Jing, Zhichun; Song, Ningjing

    2014-04-01

    Autophagy and inflammation closely interact with each other, and together, they play critical roles in bacterial infection. Leprosy is caused by the infection of Mycobacterium leprae (M. leprae). The objective of the study was to investigate the association between polymorphisms in IRGM, an autophagy gene, and susceptibility to leprosy, and identify possible functions of the polymorphism in the infection of M. leprae. Two polymorphisms in IRGM, rs4958842 and rs13361189, were tested in 412 leprosy cases and 432 healthy controls. Levels of inflammatory cytokines including interleukin 1 beta, IL-4, IL-6, and interferon gamma (INF-γ) were measured after the infection of M. leprae in the peripheral blood mononuclear cell (PBMC) of subjects with different genotypes of rs13361189. Data showed that prevalence of rs13361189TC and CC genotypes were significantly higher in leprosy patients than in healthy controls (odds ratio (OR) = 1.49, 95 % confidence interval (CI) 1.09-2.04, P = 0.012; OR = 2.58, 95 % CI 1.65-4.05, P autophagy gene polymorphism was associated with the increased risk of leprosy by affecting inflammatory cytokines.

  1. Coronary perivascular adipose tissue characteristics are related to atherosclerotic plaque size and composition : A post-mortem study

    NARCIS (Netherlands)

    Verhagen, Sandra N.; Vink, Aryan; van der Graaf, Yolanda; Visseren, Frank L. J.

    2012-01-01

    Background: Perivascular adipose tissue (pvAT) may influence atherosclerotic plaque formation. We aim to determine the association between the local amount and inflammatory properties of pvAT and the size and composition of atherosclerotic plaque in the left anterior descending artery (LAD). Methods

  2. Plasmid Transfer of Plasminogen K1-5 Reduces Subcutaneous Hepatoma Growth by Affecting Inflammatory Factors

    Directory of Open Access Journals (Sweden)

    Lea A. Koch

    2014-01-01

    Full Text Available There is evidence that plasminogen K1-5 (PlgK1-5 directly affects tumour cells and inflammation. Therefore, we analysed if PlgK1-5 has immediate effects on hepatoma cells and inflammatory factors in vitro and in vivo. In vitro, effects of plasmid encoding PlgK1-5 (pK1-5 on Hepa129, Hepa1-6, and HuH7 cell viability, apoptosis, and proliferation as well as VEGF and TNF-alpha expression and STAT3-phosphorylation were investigated. In vivo, tumour growth, proliferation, vessel density, and effects on vascular endothelial growth factor (VEGF and tumour necrosis factor alpha (TNF-alpha expression were examined following treatment with pK1-5. In vivo, pK1-5 halved cell viability; cell death was increased by up to 15% compared to the corresponding controls. Proliferation was not affected. VEGF, TNF-alpha, and STAT3-phosphorylation were affected following treatment with pK1-5. In vivo, ten days after treatment initiation, pK1-5 reduced subcutaneous tumour growth by 32% and mitosis by up to 77% compared to the controls. Vessel density was reduced by 50%. TNF-alpha levels in tumour and liver tissue were increased, whereas VEGF levels in tumours and livers were reduced after pK1-5 treatment. Taken together, plasmid gene transfer of PlgK1-5 inhibits hepatoma (cell growth not only by reducing vessel density but also by inducing apoptosis, inhibiting proliferation, and triggering inflammation.

  3. The prevalence of radiographic sacroiliitis in patients affected by inflammatory bowel disease with inflammatory low back pain

    Directory of Open Access Journals (Sweden)

    A. Lo Nigro

    2011-09-01

    Full Text Available Inflammatory bowel diseases (IBD, are Crohn’s disease (CD or ulcerative colitis (UC, are frequently complicated by joint complaints with prevalence that varies between 10 and 28 %. The IBD related arthropathy may be expressed as peripheral arthritis or axial one frequently indistinguishable from the classical ankylosing spondylitis (AS. According to ESSG criteria for spondyloarthropathy, the presence of synovitis or the inflammatory back pain (IBP in IBD patients is diagnostic for spondyloarthropathy, but for diagnosis of as also radiological criteria must be fulfilled. There are few studies regarding the radiological prevalence of sacroiliitis in patients with IBD. We examined, by plain film radiograms of pelvis, 100 sacroiliac joints (SJ of 50 IBD patients with IBP. The New York (1984 SJ radiological score with gradation from 0 to 4 was applied. Total sacroiliac score (SJS was summarized between left and right side (from 0 to 8. Fourteen patients fulfilled New York modified criteria for AS and 8 patients had unilateral 2nd grade sacroiliitis. Only 4 of 14 AS patients (28% were HLA B27 positive. Thirty patients had localized IBP, 10 extended to buttock and 4 extended to sacrum. Sixteen patients had sciatica-like extension of back pain. A difference in SJS between left and right side were observed only in CD patients (1,3± 0,8 e 0,8± 0,9 respectively; p<0,05, but not in UC (1,5± 1,2 vs 1,5± 1,3; p=ns nor in total IBD patients (1,4± 1 vs 1,2± 1,2; p=ns. Total SJS was higher in UC respect CD, but not significantly (2,9± 2,3 vs 2,1± 1,5; p=ns. Our data confirm the importance of these symptoms in patients with IBD, who need to be carefully investigated also for these aspects.

  4. 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

    ) 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...... as SUVmax (R=0.30, Puptake. We suggest that FDG uptake is a composite indicator of macrophage load, overall inflammatory activity and collagenolytic plaque...

  5. SELECTINS IN CORONARY ATHEROSCLEROTIC DISEASE:A REVIEW

    Institute of Scientific and Technical Information of China (English)

    李远方; 胡健

    2001-01-01

    The development of atherosclerotic lesions appears to be inflammatory in nature. It involves the recruitment of blood monocytes to the vascular endothelium, followed by intimal infiltration. Monocytes differentiate to macrophages, then internalize lipids to form foam cells, thus develop fatty streak lesion. A wide range of adhesion molecules governs these interactions between cells, among these molecules are selectins. Selectins mediate the first step in leukocyte adhesion at sites of inflammation or injury, characterized by rolling and tethering

  6. IL-9 signaling affects central nervous system resident cells during inflammatory stimuli.

    Science.gov (United States)

    Ding, Xiaoli; Cao, Fang; Cui, Langjun; Ciric, Bogoljub; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2015-12-01

    Interleukin (IL) 9, a dominant cytokine in Th9 cells, has been proven to play a pathogenic role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by augmenting T cell activation and differentiation; however, whether IL-9 signaling affects central nervous system (CNS)-resident cells during CNS autoimmunity remains unknown. In the present study, we found that the IL-9 receptor (IL-9R) was highly expressed in astrocytes, oligodendrocyte progenitor cells (OPCs), oligodendrocytes and microglia cells, and that its expression was significantly upregulated in brain and spinal cord during EAE. In addition, IL-9 increased chemokine expression, including CXCL9, CCL20 and MMP3, in primary astrocytes. Although IL-9 had no effect on the proliferation of microglia cells, it decreased OPC proliferation and differentiation when in combination with other pro-inflammatory cytokines, but not with IFN-γ. IL-9 plus IFN-γ promoted OPC proliferation and differentiation. These findings indicate that CNS-restricted IL-9 signaling may be involved in the pathogenesis of MS/EAE, thus providing a potential therapeutic target for future MS/EAE treatment through disruption of CNS cell-specific IL-9 signaling.

  7. Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

    Institute of Scientific and Technical Information of China (English)

    Lynnette R Ferguson; Claudia Huebner; Ivonne Petermann; Richard B Gearry; Murray L Barclay; Pieter Demmers; Alan McCulloch; Dug Yeo Han

    2008-01-01

    AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies.METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor:-238 G→A, -308 G→A and -857C→T, using a TaqmanRassay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies.RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, x2 = 17.36, P < 0.0001)increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, x2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variantdecreased the risk of ileocolonic CD (OR = 0.56, x2 =4.32, P = 0.037), and the need for a bowel resection(OR = 0.59, x2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis,(OR = 0.48, x2 = 4.86, P = 0.028).CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The-857 C/T SNP may decrease IBD risk in certain groups.Pharmaco- or nutrigenomic approaches may be desir-able for individuals with such affected genotypes.

  8. Could the homologous sequence of anti-inflammatory pentapeptide (MLIF) produced by Entamoeba histolytica in the N protein of rabies virus affect the inflammatory process?

    Science.gov (United States)

    Morales, M E; Rico, G; Gómez, J L; Alonso, R; Cortés, R; Silva, R; Giménez, J A; Kretschmer, R; Aguilar-Setién, A

    2006-02-01

    Amebiasis and rabies are public health problems, and they have in common a poor inflammatory effect in the target organs that they affect. In the GenBank, it was found that the anti-inflammatory peptide monocyte locomotion inhibitory factor (MLIF) produced by Entamoeba histolytica homologates 80%, with a fragment of the N protein of the rabies virus. We speculated if the N protein could contribute to the scant inflammatory reaction produced by rabies virus in central nervous system. The N protein was obtained and studied in vitro and in vivo. The N protein, as MLIF, inhibited the respiratory burst in human mononuclear phagocytes (43%, p<0.05), but in contrast to MLIF, it increased chemotaxis and it did not significantly inhibit delayed hypersensitivity skin reaction to 1-chloro-2-4-dinitrobenzene in guinea pigs. Therefore, the full peptide sequence has to be present or it has to be cleaved-free from the large recombinant N protein molecule (55 kDa) to become active.

  9. Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism.

    Science.gov (United States)

    Abela, Oliver G; Ahsan, Chowdhury H; Alreefi, Fadi; Salehi, Negar; Baig, Imran; Janoudi, Abed; Abela, George S

    2016-06-01

    Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis-often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy. PMID:27091328

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Management of atherosclerotic renovascular disease after Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL).

    Science.gov (United States)

    Herrmann, Sandra M S; Saad, Ahmed; Textor, Stephen C

    2015-03-01

    Many patients with occlusive atherosclerotic renovascular disease (ARVD) may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial and the Stent Placement and Blood Pressure and Lipid-Lowering for the Prevention of Progression of Renal Dysfunction Caused by Atherosclerotic Ostial Stenosis of the Renal Artery (STAR) and ASTRAL. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Although hemodynamically significant, ARVD can reduce renal blood flow and glomerular filtration rate; adaptive mechanisms preserve both cortical and medullary oxygenation over a wide range of vascular occlusion. Progression of ARVD to severe vascular compromise eventually produces cortical hypoxia, however, associated with active inflammatory cytokine release and cellular infiltration of the renal parenchyma. In such cases ARVD produces a loss of glomerular filtration rate that no longer is reversible simply by restoring vessel patency with technically successful renal revascularization. Each of these trials reported adverse renal functional outcomes ranging between 16 and 22% over periods of 2-5 years of follow-up. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of ARVD for clinical nephrologists in the context of recent randomized clinical trials and experimental research. PMID:24723543

  12. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    International Nuclear Information System (INIS)

    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

  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

    BACKGROUND: Through several observational and mechanistic studies, microbial infection is known to promote cardiovascular disease. Direct infection of the vessel wall, along with the cardiovascular risk factors, is hypothesized to play a key role in the atherogenesis by promoting an inflammatory...... response leading to endothelial dysfunction and generating a proatherogenic and prothrombotic environment ultimately leading to clinical manifestations of cardiovascular disease, e.g., acute myocardial infarction or stroke. There are many reports of microbial DNA isolation and even a few studies of viable...... 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...

  14. 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.

  15. Immunosuppression Adversely Affects TST but Not IGRAs in Patients with Psoriasis or Inflammatory Musculoskeletal Diseases

    Directory of Open Access Journals (Sweden)

    Esko Tavast

    2012-01-01

    Full Text Available The performance of the interferon gamma release assays (IGRAs and tuberculin skin test (TST was reviewed retrospectively in patients with psoriasis, inflammatory musculoskeletal diseases, or miscellaneous inflammatory conditions. The study was carried out over a 22-month period using 109 records of patients with psoriasis (=21, musculoskeletal disease (=74, or other inflammatory conditions (=14. Forty-four (48% of 109 patients were on immunosuppressive therapy and 38/109 (35% on systemic glucocorticoid therapy. The agreement between the IGRAs was substantial (=0.71 whilst that between the IGRAs and TST was low (=0.32. Logistic regression models revealed that IGRAs associated with risk factors for latent tuberculosis infection better than TST. TST was influenced by age, BCG vaccination, sex, and glucocorticoid therapy. We found that IGRAs performed equally well with low level of indeterminate results (1-2%. IGRAs were superior to TST because the latter was influenced by BCG-vaccination status and immunosuppressive therapy.

  16. Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders

    DEFF Research Database (Denmark)

    Vinberg, Maj; Weikop, Pia; Olsen, Niels Vidiendal;

    2016-01-01

    were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (sub-study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS)⩽14) (sub-study 2). In both...... in verbal memory. CONCLUSIONS: Repeated EPO infusions had no effect on IL-6 and IL-18 levels but produced a modest increase in hsCRP levels in patients with TRD. Changes over time in inflammatory markers were not correlated with changes in cognition suggesting that modulation of the inflammatory pathway...

  17. Ventilation during cardiopulmonary bypass did not attenuate inflammatory response or affect postoperative outcomes

    OpenAIRE

    Durukan, Ahmet Baris; Gurbuz, Hasan Alper; Ucar, Halil Ibrahim; Yorgancioglu, Cem; Salman, Nevriye; Utku Unal, Ertekin

    2013-01-01

    Introduction Cardiopulmonary bypass causes a series of inflammatory events that have adverse effects on the outcome. The release of cytokines, including interleukins, plays a key role in the pathophysiology of the process. Simultaneously, cessation of ventilation and pulmonary blood flow contribute to ischaemia–reperfusion injury in the lungs when reperfusion is maintained. Collapse of the lungs during cardiopulmonary bypass leads to postoperative atelectasis, which correlates with the amount...

  18. 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....

  19. The prolactin receptor is expressed in macrophages within human carotid atherosclerotic plaques: a role for prolactin in atherogenesis?

    NARCIS (Netherlands)

    A. Reuwer; M. van Eijk; F. Houttuijn-Bloemendaal; C. van der Loos; N. Claessen; P. Teeling; J.J. Kastelein; J. Hamann; V. Goffin; J. von der Thüsen; M. Twickler; J. Aten

    2011-01-01

    Atherosclerotic vascular disease is the consequence of a chronic inflammatory process, and prolactin has been shown to be a component of the inflammatory response. Additionally, recent studies indicate that prolactin contributes to an atherogenic phenotype. We hypothesized that this may be the resul

  20. 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 ...

  1. Accumulation of myeloperoxidase-positive neutrophils in atherosclerotic lesions in LDLR-/- mice

    NARCIS (Netherlands)

    van Leeuwen, Marcella; Gijbels, Marion J. J.; Duijvestijn, Adriaan; Smook, Marjan; van de Gaar, Marie Jose; Heeringa, Peter; de Winther, Menno P. J.; Tervaert, Jan Willem Cohen

    2008-01-01

    Objective-Atherosclerosis is a chronic inflammatory disease in which the immune system plays an important role. Neutrophils have not been thoroughly studied in the context of atherogenesis. Here, we investigated neutrophils in the development of murine atherosclerotic lesions. Methods and Results-LD

  2. Blueberry, blackberry, and blackcurrant differentially affect plasma lipids and pro-inflammatory markers in diet-induced obesity mice

    Science.gov (United States)

    Kim, Bohkyung; Lee, Sang Gil; Park, Young-Ki; Ku, Chai Siah; Pham, Tho X.; Wegner, Casey J.; Yang, Yue; Koo, Sung I.; Chun, Ock K.

    2016-01-01

    BACKGROUND/OBJECTIVES Evidence indicates that berry anthocyanins are anti-atherogenic, antioxidant, and anti-inflammatory. However, berries differ vastly in their anthocyanin composition and thus potentially in their biological and metabolic effects. The present study compared hypolipidemic, antioxidant, and anti-inflammatory properties of blueberry (BB), blackberry (BK), and blackcurrant (BC) in a diet-induced obesity (DIO) mouse model. MATERIALS/METHODS Male C57BL/6J mice were fed a high fat (HF; 35% fat, w/w) control diet or a HF diet supplemented with freeze-dried 5% BB, 6.3% BK or 5.7% BC for 12 weeks (10 mice/group) to achieve the same total anthocyanin content in each diet. Plasma lipids, antioxidant status and pro-inflammatory cytokines were measured. The expression of genes involved in antioxidant defense, inflammation, and lipid metabolism was determined in the liver, epididymal adipose tissue, proximal intestine, and skeletal muscle. Histological analysis was performed to identify crown-like structure (CLS) in epididymal fat pads to determine macrophage infiltration. RESULTS No differences were noted between the control and any berry-fed groups in plasma levels of liver enzymes, insulin, glucose, ferric reducing antioxidant power, superoxide dismutase, and tumor necrosis factor α. However, BK significantly lowered plasma triglyceride compared with the HF control and other berries, whereas BC significantly reduced F4/80 mRNA and the number of CLS in the epididymal fat pad, indicative of less macrophage infiltration. CONCLUSIONS The present study provides evidence that BB, BK and BC with varying anthocyanin composition differentially affect plasma lipids and adipose macrophage infiltration in DIO mice, but with no differences in their antioxidant capacity and anti-inflammatory potential.

  3. 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...

  4. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules

    Directory of Open Access Journals (Sweden)

    Das Undurti N

    2008-10-01

    Full Text Available Abstract Lowering plasma low density lipoprotein-cholesterol (LDL-C, blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a β blocker, and an angiotensin converting enzyme (ACE inhibitor each at half standard dose; folic acid; and aspirin-called as polypill- was estimated to reduce cardiovascular events by ~80%. Essential fatty acids (EFAs and their long-chain metabolites: γ-linolenic acid (GLA, dihomo-GLA (DGLA, arachidonic acid, eicosapentaenoic acid (EPA, and docosahexaenoic acid (DHA and other products such as prostaglandins E1 (PGE1, prostacyclin (PGI2, PGI3, lipoxins (LXs, resolvins, protectins including neuroprotectin D1 (NPD1 prevent platelet aggregation, lower blood pressure, have anti-arrhythmic action, reduce LDL-C, ameliorate the adverse actions of homocysteine, show anti-inflammatory actions, activate telomerase, and have cytoprotective properties. Thus, EFAs and their metabolites show all the classic actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules present in almost all tissues, have no significant or few side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and infants, children, and adults; and have been known to reduce the incidence cardiovascular diseases including stroke. In addition, various EFAs and their long-chain metabolites not only enhance nitric oxide generation but also react with nitric oxide to yield their respective nitroalkene derivatives that produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and possess PPAR-γ ligand activity and release NO, thus prevent platelet aggregation, thrombus formation, atherosclerosis, and cardiovascular diseases. Based on these evidences, I propose that a rational combination of ω-3 and ω-6 fatty acids and the co

  5. Imaging Atherosclerotic Plaque Calcification: Translating Biology.

    Science.gov (United States)

    Bailey, Grant; Meadows, Judith; Morrison, Alan R

    2016-08-01

    Calcification of atherosclerotic lesions was long thought to be an age - related, passive process, but increasingly data has revealed that atherosclerotic calcification is a more active process, involving complex signaling pathways and bone-like genetic programs. Initially, imaging of atherosclerotic calcification was limited to gross assessment of calcium burden, which is associated with total atherosclerotic burden and risk of cardiovascular mortality and of all cause mortality. More recently, sophisticated molecular imaging studies of the various processes involved in calcification have begun to elucidate information about plaque calcium composition and consequent vulnerability to rupture, leading to hard cardiovascular events like myocardial infarction. As such, there has been renewed interest in imaging calcification to advance risk assessment accuracy in an evolving era of precision medicine. Here we summarize recent advances in our understanding of the biologic process of atherosclerotic calcification as well as some of the molecular imaging tools used to assess it. PMID:27339750

  6. Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis

    Directory of Open Access Journals (Sweden)

    Ippokratis Pountos

    2012-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients.

  7. Surgery of infrarenal inflammatory aneurysm of abdominal aorta infected with methicillin resistant Staphylococcus aureus in a patient undergoing haemodialysis

    Directory of Open Access Journals (Sweden)

    Babić Srđan

    2008-01-01

    Full Text Available INTRODUCTION Inflammatory abdominal aortic aneurysm accounts for 5% to 10% of all cases of abdominal aortic aneurysm and differs from typical atherosclerotic abdominal aortic aneurysm in many important ways. Although both inflammatory and atherosclerotic abdominal aortic aneurysms most commonly affect the infrarenal portion of the abdominal aorta, patients with the inflammatory variant are younger and usually symptomatic, chiefly from back or abdominal pain. Unlike patients with atherosclerotic abdominal aortic aneurysm, most with the inflammatory variant have an elevated erythrocyte sedimentation rate or abnormalities of other serum inflammatory markers. Computed tomography and magnetic resonance imaging are both sensitive for demonstrating the cuff of soft tissue inflammation surrounding the aneurysm that is characteristic of inflammatory abdominal aortic aneurysm. Inflammatory abdominal aortic aneurysm can be primarily infected by degenaration of an infected artery (in less than 1% of cases, or can become secondary infected in the already existing aneurysm. Secondary infection of the pre-existing aneurysm has big influence on treatment choice, but is also rare. Clinically non-symptomatic infection, also known as bacterial collonisation, can be very frequent, regarding a greatly increased number of positive intraoperative findings (10-15%. Prolonged intravascular catheterization, vascular grafting, repeated punctures with large bore needles, and decreased immune defense mechanism make uraemic patients undergoing hemodialysis more likely to develop Staphylococcus aureus bacteraemia and its complications. CASE OUTLINE The case shows a gigantic inflammatory aneurysm of the abdominal aorta, localized infrarenally, which was solved successfully by resection of the aneurysm of the abdominal aorta, and interposition of Dacron tubular graft 22 mm. Bacterial examination of the aneurysmal sac was positive: methicillin-resistent Staphylococcus aureus was

  8. CAROTID ATHEROSCLEROTIC LESION IN YOUNG PATIENTS

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. 1-Methylnicotinamide and nicotinamide: two related anti-inflammatory agents that differentially affect the functions of activated macrophages

    OpenAIRE

    Biedroń, Rafał; Ciszek, Marta; Tokarczyk, Marianna; Bobek, Małgorzata; Kurnyta, Maria; Słominska, Ewa M.; Smoleński, Ryszard T.; Marcinkiewicz, Janusz

    2008-01-01

    Introduction: 1-Methylnicotinamide (MNA), a major metabolite of nicotinamide (NA), is known to exert anti-inflammatory effects in vivo. Treatment of inflammatory skin diseases by topical application of MNA provides certain advantages over the use of NA. However, in contrast to NA, the molecular mechanisms of the anti-inflammatory properties of MNA are not well known. In this study the influence of exogenous MNA and NA in vivo on the generation of inflammatory mediators by macrophages (Mϕ) was...

  11. JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells

    International Nuclear Information System (INIS)

    JMJD2A is a lysine trimethyl-specific histone demethylase that is highly expressed in a variety of tumours. The role of JMJD2A in tumour progression remains unclear. The objectives of this study were to identify JMJD2A-regulated genes and understand the function of JMJD2A in p53-null neuroectodermal stem cells (p53−/− NE-4Cs). We determined the effect of LPS as a model of inflammation in p53−/− NE-4Cs and investigated whether the epigenetic modifier JMJD2A alter the expression of tumourigenic inflammatory genes. Global gene expression was measured in JMJD2A knockdown (kd) p53−/− NE-4Cs and in LPS-stimulated JMJD2A-kd p53−/− NE-4C cells. JMJD2A attenuation significantly down-regulated genes were Cdca2, Ccnd2, Ccnd1, Crebbp, IL6rα, and Stat3 related with cell cycle, proliferation, and inflammatory-disease responses. Importantly, some tumour-suppressor genes including Dapk3, Timp2 and TFPI were significantly up-regulated but were not affected by silencing of the JMJD2B. Furthermore, we confirmed the attenuation of JMJD2A also down-regulated Cdca2, Ccnd2, Crebbp, and Rest in primary NSCs isolated from the forebrains of E15 embryos of C57/BL6J mice with effective p53 inhibitor pifithrin-α (PFT-α). Transcription factor (TF) motif analysis revealed known binding patterns for CDC5, MYC, and CREB, as well as three novel motifs in JMJD2A-regulated genes. IPA established molecular networks. The molecular network signatures and functional gene-expression profiling data from this study warrants further investigation as an effective therapeutic target, and studies to elucidate the molecular mechanism of JMJD2A-kd-dependent effects in neuroectodermal stem cells should be performed. - Highlights: • Significant up-regulation of epigenetic modifier JMJD2A mRNA upon LPS treatment. • Inhibition of JMJD2A attenuated key inflammatory and tumourigenic genes. • Establishing IPA based functional genomics in JMJD2A-attenuated p53−/− NE4C cells. • Finding JMJD2

  12. JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Das, Amitabh, E-mail: amitabhdas.kn@gmail.com [Department of Bionanotechnology, Hanyang University, Seoul 133-791 (Korea, Republic of); Chai, Jin Choul, E-mail: jincchai@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Jung, Kyoung Hwa, E-mail: khjung2@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Das, Nando Dulal, E-mail: nando.hu@gmail.com [Clinical Research Centre, Inha University School of Medicine, Incheon 400-711 (Korea, Republic of); Kang, Sung Chul, E-mail: gujiju11@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Lee, Young Seek, E-mail: yslee@hanyang.ac.kr [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Seo, Hyemyung, E-mail: hseo@hanyang.ac.kr [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Chai, Young Gyu, E-mail: ygchai@hanyang.ac.kr [Department of Bionanotechnology, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of)

    2014-11-01

    JMJD2A is a lysine trimethyl-specific histone demethylase that is highly expressed in a variety of tumours. The role of JMJD2A in tumour progression remains unclear. The objectives of this study were to identify JMJD2A-regulated genes and understand the function of JMJD2A in p53-null neuroectodermal stem cells (p53{sup −/−} NE-4Cs). We determined the effect of LPS as a model of inflammation in p53{sup −/−} NE-4Cs and investigated whether the epigenetic modifier JMJD2A alter the expression of tumourigenic inflammatory genes. Global gene expression was measured in JMJD2A knockdown (kd) p53{sup −/−} NE-4Cs and in LPS-stimulated JMJD2A-kd p53{sup −/−} NE-4C cells. JMJD2A attenuation significantly down-regulated genes were Cdca2, Ccnd2, Ccnd1, Crebbp, IL6rα, and Stat3 related with cell cycle, proliferation, and inflammatory-disease responses. Importantly, some tumour-suppressor genes including Dapk3, Timp2 and TFPI were significantly up-regulated but were not affected by silencing of the JMJD2B. Furthermore, we confirmed the attenuation of JMJD2A also down-regulated Cdca2, Ccnd2, Crebbp, and Rest in primary NSCs isolated from the forebrains of E15 embryos of C57/BL6J mice with effective p53 inhibitor pifithrin-α (PFT-α). Transcription factor (TF) motif analysis revealed known binding patterns for CDC5, MYC, and CREB, as well as three novel motifs in JMJD2A-regulated genes. IPA established molecular networks. The molecular network signatures and functional gene-expression profiling data from this study warrants further investigation as an effective therapeutic target, and studies to elucidate the molecular mechanism of JMJD2A-kd-dependent effects in neuroectodermal stem cells should be performed. - Highlights: • Significant up-regulation of epigenetic modifier JMJD2A mRNA upon LPS treatment. • Inhibition of JMJD2A attenuated key inflammatory and tumourigenic genes. • Establishing IPA based functional genomics in JMJD2A-attenuated p53{sup

  13. Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males

    Directory of Open Access Journals (Sweden)

    Rimbach Gerald

    2011-05-01

    Full Text Available Abstract Background Human paraoxonase 1 (PON1 is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary heart diseases and underlying atherogenesis. The common PON1 Q192R polymorphism (rs662, A>G, a glutamine to arginine substitution at amino acid residue 192, has been analyzed in numerous association studies as a genetic marker for coronary heart diseases, however, with controversial results. Findings To get a better understanding about the pathophysiological function of PON1, we analyzed the relationships between the Q192R polymorphism, serum paraoxonase activity and serum biomarkers important for atherogenesis. Genotyping a cohort of 49 healthy German males for the Q192R polymorphism revealed an allele distribution of 0.74 and 0.26 for the Q and R allele, respectively, typical for Caucasian populations. Presence of the R192 allele was found to be associated with a significantly increased paraoxonase enzyme activity of 187.8 ± 11.4 U/l in comparison to the QQ192 genotype with 60.5 ± 4.9 U/l. No significant differences among the genotypes were found for blood pressure, asymmetric dimethylarginine, LDL, HDL, triglycerides, and cholesterol. As expected, MIP-2 alpha a cytokine rather not related to atherosclerosis is not affected by the PON1 polymorphism. In contrast to that, the pro-inflammatory cytokine TNF-alpha is enhanced in R192 carriers (163.8 ± 24.7 pg/ml vs 94.7 ± 3.2 pg/ml in QQ192 carriers. Conclusions Our findings support the hypothesis that the common PON1 R192 allele may be a genetic risk factor for atherogenesis by inducing chronic low-grade inflammation.

  14. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

    2015-11-01

    Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities.

  15. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

    2015-11-01

    Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities. PMID:26118693

  16. Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression.

    Science.gov (United States)

    Woollard, Kevin J; Lumsden, Natalie G; Andrews, Karen L; Aprico, Andrea; Harris, Emma; Irvine, Jennifer C; Jefferis, Ann-maree; Fang, Lu; Kanellakis, Peter; Bobik, Alex; Chin-Dusting, Jaye P F

    2014-01-01

    Soluble P-selectin (sP-selectin), a biomarker of inflammatory related pathologies including cardiovascular and peripheral vascular diseases, also has pro-atherosclerotic effects including the ability to increase leukocyte recruitment and modulate thrombotic responses in vivo. The current study explores its role in progressing atherosclerotic plaque disease. Apoe-/- mice placed on a high fat diet (HFD) were given daily injections of recombinant dimeric murine P-selectin (22.5 µg/kg/day) for 8 or 16 weeks. Saline or sE-selectin injections were used as negative controls. In order to assess the role of sP-selectin on atherothrombosis an experimental plaque remodelling murine model, with sm22α-hDTR Apoe-/- mice on a HFD in conjunction with delivery of diphtheria toxin to induce targeted vascular smooth muscle apoptosis, was used. These mice were similarly given daily injections of sP-selectin for 8 or 16 weeks. While plaque mass and aortic lipid content did not change with sP-selectin treatment in Apoe-/- or SM22α-hDTR Apoe-/- mice on HFD, increased plasma MCP-1 and a higher plaque CD45 content in Apoe-/- HFD mice was observed. As well, a significant shift towards a more unstable plaque phenotype in the SM22α-hDTR Apoe-/- HFD mice, with increased macrophage accumulation and lower collagen content, leading to a lower plaque stability index, was observed. These results demonstrate that chronically raised sP-selectin favours progression of an unstable atherosclerotic plaque phenotype.

  17. 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.

  18. Calculation of arterial wall temperature in atherosclerotic arteries: effect of pulsatile flow, arterial geometry, and plaque structure

    Directory of Open Access Journals (Sweden)

    Kim Taehong

    2007-03-01

    Full Text Available Abstract Background This paper presents calculations of the temperature distribution in an atherosclerotic plaque experiencing an inflammatory process; it analyzes the presence of hot spots in the plaque region and their relationship to blood flow, arterial geometry, and inflammatory cell distribution. Determination of the plaque temperature has become an important topic because plaques showing a temperature inhomogeneity have a higher likelihood of rupture. As a result, monitoring plaque temperature and knowing the factors affecting it can help in the prevention of sudden rupture. Methods The transient temperature profile in inflamed atherosclerotic plaques is calculated by solving an energy equation and the Navier-Stokes equations in 2D idealized arterial models of a bending artery and an arterial bifurcation. For obtaining the numerical solution, the commercial package COMSOL 3.2 was used. The calculations correspond to a parametric study where arterial type and size, as well as plaque geometry and composition, are varied. These calculations are used to analyze the contribution of different factors affecting arterial wall temperature measurements. The main factors considered are the metabolic heat production of inflammatory cells, atherosclerotic plaque length lp, inflammatory cell layer length lmp, and inflammatory cell layer thickness dmp. Results The calculations indicate that the best location to perform the temperature measurement is at the back region of the plaque (0.5 ≤ l/lp ≤ 0.7. The location of the maximum temperature, or hot spot, at the plaque surface can move during the cardiac cycle depending on the arterial geometry and is a direct result of the blood flow pattern. For the bending artery, the hot spot moves 0.6 millimeters along the longitudinal direction; for the arterial bifurcation, the hot spot is concentrated at a single location due to the flow recirculation observed at both ends of the plaque. Focusing on the

  19. Cardiovascular magnetic resonance in carotid atherosclerotic disease

    OpenAIRE

    Chen Huijun; Wang Jinnan; Li Rui; Ferguson Marina S; Kerwin William S; Dong Li; Canton Gador; Hatsukami Thomas S; Yuan Chun

    2009-01-01

    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 promi...

  20. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    International Nuclear Information System (INIS)

    Increased expression of αvβ3/αvβ5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel 68Ga-DOTA-RGD peptide binds with high affinity to αvβ3/αvβ5 integrin. The aim of this study was to investigate the uptake of the 68Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered 68Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR-/-ApoB100/100 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 68Ga. The tracer had reasonably good specific radioactivity (8.7 ± 1.1 GBq/μmol) and was quite stable in vivo. According to ex vivo biodistribution results, 68Ga-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 68Ga-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 68Ga-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.)

  1. Uptake of 68gallium in atherosclerotic plaques in LDLR-/-ApoB100/100 mice

    OpenAIRE

    Silvola, Johanna MU; Laitinen, Iina; Sipilä, Henri J; Laine, V Jukka O; Leppänen, Pia; Ylä-Herttuala, Seppo; Knuuti, Juhani; Roivainen, Anne

    2011-01-01

    Background Atherosclerosis is a chronic inflammatory disease of artery wall characterized by infiltration of monocytes into subendothelial space and their differentiation into macrophages. Since rupture-prone plaques commonly contain high amounts of activated macrophages, imaging of the macrophage content may provide a useful tool for the evaluation of plaque vulnerability. The purpose of this study was to explore the uptake of 68gallium (68Ga) in atherosclerotic plaques in mice. Methods Upta...

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

    Institute of Scientific and Technical Information of China (English)

    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

    Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. 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. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease.

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

    OpenAIRE

    Son, Dong Ju; Kim, Soo Yeon; Han, Seong Su; Kim, Chan Woo; Kumar, Sandeep; Park, Byeoung Soo; Lee, Sung Eun; Yun, Yeo Pyo; Jo, Hanjoong; Park, Young Hyun

    2012-01-01

    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 significant...

  4. Coordination of cortisol response to social evaluative threat with autonomic and inflammatory responses is moderated by stress appraisals and affect.

    Science.gov (United States)

    Laurent, Heidemarie K; Lucas, Todd; Pierce, Jennifer; Goetz, Stefan; Granger, Douglas A

    2016-07-01

    Recent approaches to stress regulation have emphasized coordination among multiple biological systems. This study builds on evidence that hypothalamic-pituitary-adrenal (HPA) axis activity should be considered in coordination with other stress-sensitive biological systems to characterize healthy responses. Healthy African-Americans (n=115) completed the Trier Social Stress Test, and biological responses were assessed through salivary cortisol, dehydroepiandrosterone-sulfate (DHEA-S), alpha amylase (sAA), and C-reactive protein (sCRP). Multilevel modeling demonstrated that cortisol responses typically aligned with changes in DHEA-S, sAA, and sCRP across the session. At the same time, the degree of cortisol coordination with sAA and sCRP varied by participants' subjective stress following the task; participants with higher secondary stress appraisals showed greater cortisol-sAA alignment, whereas those experiencing more negative affect showed greater cortisol-sCRP alignment. Results highlight the importance of a multisystem approach to stress and suggest that positive HPA axis coordination with the autonomic response, but not with the immune/inflammatory response, may be adaptive.

  5. 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

  6. Symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) with concurrent contralateral vertebral atherosclerotic diseases in 88 patients treated with the intracranial stenting

    International Nuclear Information System (INIS)

    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. The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease.

    Science.gov (United States)

    Zhu, Ping; Sun, Weiwei; Zhang, Chenliang; Song, Zhiyuan; Lin, Shu

    2016-10-01

    With average life expectancy rising greatly, the incidence rate of arteriosclerotic cardiovascular disease (ASCVD) has significantly increased. The heart disease has now become the number one killer that threatens the global population health, the second is stroke. It will be of great significance to investigate the underlying pathophysiological mechanisms of ASCVD in order to promote effective prevention and treatment. The neuropeptide Y (NPY) has now been discovered for more than thirty years and is widely distributed in the central nervous system (CNS) and peripheral tissues. By combining with certain receptors, NPY performs a variety of physiological functions, including the regulation of food intake, cardiovascular effects, development, hormonal secretion, sexual behavior, biological rhythms, temperature and emotion. In ASCVD, increased peripheral NPY was involved in the pathophysiological process of atherosclerosis through affecting the vascular endothelial dysfunction, the formation of foam cells, the proliferation of vascular smooth muscle cells, the local inflammatory response of plaques and the activation and aggregation of platelets. Via central and/or the peripheral nervous system, increased NPY was associated with dyslipidemia, hypertension, obesity, diabetes, impaired glucose tolerance, and smoking which are all risk factors for ASCVD. In this review, we summarize the role of neuropeptide Y in the development of atherosclerotic cardiovascular disease. PMID:27389447

  8. [Atherosclerotic renal artery disease management update].

    Science.gov (United States)

    Meier, Pascal; Haesler, Erik; Teta, Daniel; Qanadli, Salah Dine; Burnier, Michel

    2009-02-01

    In the case of atherosclerotic renal artery disease, the best conclusive results lie principally not in the degree of the stenosis but rather in the degree the renal parenchymal disease beyond the stenosis itself. These determining factors involve the controlling of the patients blood pressure, the improvement in the renal function and the beneficial results to the cardiovascular system. Besides the indispensable medical treatment, a revascularisation by angioplasty may be indicated. This procedure with or without vascular stent often allows satisfactory angiographic results. A treatment by surgical revascularisation is only recommended in the case of extensive atherosclerotic lesions of the aorta, complex lesions of the latter or an abdominal aortic aneurism. Although the frequency of restenosis of angioplasty with stent remains extremely low, the risk of cholesterol emboli due to the diffuse atherosclerotic lesions of the abdominal aorta, must be considered at the time of each aortic catheterization. The therapeutic approach of atherosclerotic renal artery disease must be dictated by the whole cardiovascular risk factors and by the threat of target organs. The control of the blood pressure and the maintenance of the renal function must be integrated in the decisional algorithm as well as the possible risks in carrying out an eventual revascularisation procedure. Finally, the renal angioplasty should in numerous situations be integrated in the overall assumption of responsibility of the atherosclerotic vascular diseases, and should be part of the medical treatment. Several questions still do exist; at what moment an atherosclerotic renal artery stenosis should and e considered critical, and which procedure should be considered for which patient? The purpose of this review is to propose a decisional tool for individualized treatments in the light of results from randomized and controlled studies. PMID:18815087

  9. Anti-Inflammatory (IL-10 Levels and Affects the Survival of Prostate Carcinoma Patients: An Explorative Study in North Indian Population

    Directory of Open Access Journals (Sweden)

    Shailendra Dwivedi

    2014-01-01

    Full Text Available Objective. Inflammation is an important hallmark of all cancers and net inflammatory response is determined by a delicate balance between pro- and anti-inflammatory cytokines, which may be affected by tobacco exposure, so the present study was designed to explore the effect of various modes of tobacco exposure on interleukin-12 (IL-12 and interleukin-10 (IL-10 inflammatory cytokine levels and survival in prostate carcinoma (PCa patients. Methods. 285 cancer patients and equal controls with 94 BPH (benign prostatic hyperplasia were recruited; baseline levels of serum IL-12 and IL-10 were measured and analyzed in various tobacco exposed groups by appropriate statistical tool. Five-year survivals of patients were analyzed by Log-rank (Mantel-Cox test (graph pad version 5. Results. The expression of serum proinflammatory (IL-12 and anti-inflammatory (IL-10 cytokines was correlated with tobacco exposed group as smokers, chewers, and alcohol users have shown significantly higher levels (P<0.001 with significantly lower median survivals (27.1 months, standard error = 2.86, and 95% CI: 21.4–32.62; than nonusers. Stages III and IV of tobacco addicted patients have also shown significantly increased levels of IL-12 and IL-10. Conclusions. IL-12 and IL-10 seem to be affected by various modes of tobacco exposure and inflammation also affects median survival of cancer patients.

  10. Magnetic force microscopy of atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Alexeeva T.A.

    2014-03-01

    Full Text Available 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. The fragments of atherosclerotic vessels with elements of immature plaque were taken during the coiled artery bypass surgery by alloprosthesis. As the result of investigation we found magnetically ordered phase of endogenous origin in the fragment of solid plaque of mixed structure. This phase is presents biogenic magnetic nanoparticles and their clusters with average size characteristic of 200-400 nm.

  11. Factors Affecting the Efficacy of Nonsteroidal Anti-inflammatory Drugs in Preventing Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis

    Science.gov (United States)

    Rustagi, Tarun; Njei, Basile

    2016-01-01

    Objectives To identify the factors affecting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Methods We systematically searched databases for relevant studies published from inception to November 2013. Results A meta-analysis of 11 randomized trials (n = 2497) revealed a significant reduction in PEP in patients who received NSAIDs compared with that in patients who received placebo (relative risk [RR], 0.59; 95% confidence interval [CI], 0.41–0.85; P = 0.005). In subgroup analysis by treatment type, indomethacin had no significant effect (RR, 0.66; 95% CI, 0.38–1.15; P = 0.14), whereas other NSAIDs showed significant benefit (RR, 0.51; 95% CI, 0.29–0.91; P = 0.02). Only rectal administration significantly reduced the incidence of PEP (RR, 0.43; 95% CI, 0.32–0.58; P < 0.00001). The risk for PEP was the lowest among patients who received NSAIDs before ERCP (RR, 0.48; 95% CI, 0.29–0.78; P = 0.003). NSAIDs did not significantly reduce the risk of PEP in men (RR, 0.61; 95% CI, 0.34–1.09), patients with sphincter of Oddi dysfunction (RR, 0.98; 95% CI, 0.38–2.54), or patients with pancreatic duct injection (RR, 0.64; 95% CI, 0.35–1.18). Conclusions Rectal administration of NSAIDs (especially diclofenac), before ERCP, seemed to be the most effective strategy for preventing PEP. PMID:26168316

  12. [Changes in proinflammatory cytokine and destructive metalloproteinase levels during formation of unstable atherosclerotic plaque].

    Science.gov (United States)

    Ragino, Iu I; Cherniavskiĭ, A M; Polonskaia, Ia V; Volkov, A M; Semaeva, E V; Tsymbal, S Iu; Voevoda, M I

    2009-01-01

    We studied men with coronary atherosclerosis without acute coronary syndrome and determined typical valuable parameters of inflammatory (tumor necrotic factor, antagonist of receptor to interleukin [IL] 1, IL 6, IL 8, monocytes chemotactic protein 1, endothelial monocytes activating protein II), and destructive (matrix metalloproteinase [MMP] 3, MMP 7, MMP 9, tissue inhibitor of metalloproteinase) processes at consecutive stages of formation of coronary atherosclerotic plaque: "normal intimal tissue --> lipid stain --> early stable plaque --> unstable vulnerable plaque stable plaque with fibrosis", and in 3 types of unstable plaques (lipid type, inflammatory erosive type, necrotic type). PMID:19656094

  13. N-Butanol Extract from Melilotus suaveolens Ledeb Affects Pro- and Anti-Inflammatory Cytokines and Mediators

    Directory of Open Access Journals (Sweden)

    Lei Zhao

    2010-01-01

    Full Text Available Melilotus suaveolens Ledeb is a traditional medicinal plant for treating inflammation-related disease. This explores the inner anti-inflammatory mechanism of n-butanol extract from M. suaveolens Ledeb. Inflammatory cellular model was established by lipopolysaccharide intervention on RAW264.7 cell line. Levels of secreted cytokines TNF-α, IL-1β, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-α, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, activation of NF-κB and ingredients in the extract were assayed by ELISA, real time quantitative PCR, western blot, immunocytochemical test and HPLC fingerprint test, respectively. As a result, the extract could not only markedly reduce the production of pro-inflammatory mediators to different extents by blocking NF-κB activation but also promote the release of anti-inflammatory mediator HO-1 significantly. Each 1 g extract contained 0.023531 mg coumarin and another two high polar ingredients, probably saponins. It can be concluded that the extract has similar effects on antagonizing pro-inflammatory mediators and cytokines like Dexamethasone, and has effects on promoting the production of anti-inflammatory mediators.

  14. LPS-induced neonatal stress in mice affects the response profile to an inflammatory stimulus in an age and sex-dependent manner.

    Science.gov (United States)

    Barth, Cristiane R; Luft, Carolina; Funchal, Giselle A; de Oliveira, Jarbas R; Porto, Bárbara N; Donadio, Márcio V F

    2016-07-01

    The aim of this study is to evaluate the response to an inflammatory stimulus in mice exposed to LPS-induced neonatal stress at different ages and sexes. Balb/c mice were submitted to intraperitoneal injections on postnatal days 3 and 10 with lipopolysaccharide (nLPS) or saline solution (nSal). At 21 or 60 days, either saline solution was injected or an inflammatory stimulus was induced by the injection of 1% carrageenan. Inflammatory cytokines, reactive oxygen species, and neutrophil extracellular traps (NETs) production were measured in peritoneal fluid. LPS-induced neonatal stress can reduce inflammatory cytokines in males and females. An increase in NETs production was observed when 60 day nLPS animals were compared to 21 day mice in both sexes. The ROS production was not affected by neonatal stress. The results shown here indicate that LPS-induced neonatal stress can alter cytokine production in response to inflammatory stimuli at different ages, in a sex-dependent effect. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 600-613, 2016. PMID:26956468

  15. Lipidome of atherosclerotic plaques from hypercholesterolemic rabbits.

    Science.gov (United States)

    Bojic, Lazar A; McLaren, David G; Shah, Vinit; Previs, Stephen F; Johns, Douglas G; Castro-Perez, Jose M

    2014-12-15

    The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC) for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome.

  16. Lipidome of Atherosclerotic Plaques from Hypercholesterolemic Rabbits

    Directory of Open Access Journals (Sweden)

    Lazar A. Bojic

    2014-12-01

    Full Text Available The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome.

  17. Animal model of high cholesterol atherosclerotic erectile dysfunction and mechanism of atherosclerotic erectile dysfunction

    Institute of Scientific and Technical Information of China (English)

    Guo-ShengYang; Zhao-DianChen; Hong-JuWang

    2004-01-01

    Aim: To establish the animal model of atherosclerotic erectile dysfunction (ED) induced by high cholesterol diet and explore the mechanism of atherosclerotic ED. Methods: Thirty male rabbits were divided at random into two groups: the normal diet (ND)group (n=10) and the high cholesterol (HCH) group fed with 1.5% cholesterol diet (n=20). Serum total cholesterol, plaque areas of the ascending aorta,

  18. Induction of the Chemokines CCL3α, CCL3α and CCL5 in Atherosclerotic Patients

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    Alyaa Mousa

    2007-01-01

    Full Text Available Chemokines recruit immune cells to inflammatory sites and promote the process of inflammation. The role of these mediators in the disease process in atherosclerosis is not fully studied. The spontaneous mRNA expression and intracellular protein production of the potential inflammatory chemokines CCL3 and CCL3 (macrophage- inflammatory protein-1and ; CCR3 ligand and CCL5 (regulated upon activation, normal T cell expressed and secreted (RANTES; CCR5 ligand in atherosclerotic patients was examined together with the effects of the chlamydial antigen HSP60 and LPS on the gene expression and protein induction of these mediators. Detection of chemokine mRNA and protein levels was assessed by in situ hybridization and immunohistochemistry respectively. The examined chemokines were detected at significantly high levels on atherosclerotic patients compared to healthy controls at both mRNA and protein levels. Stimulation with HSP60 and LPS from Chlamydia pneumoniae (C. pneumoniae and E. coli showed increased numbers of CCL3, CCL3 and CCL5 mRNA expressing cells in patients compared to health controls. Protein translation of these chemokines was depicted in correspondence to the mRNA gene expression for all examined chemokines spontaneously and after stimulation with chlamydial HSP60 and LPS and E. coli LPS. Thus, the herein data demonstrate the induction of potential inflammatory chemokines in atherosclerotic patients and that bacterial antigens play a role in the immunopathologic events in this disease by generating more inflammatory mediators.

  19. 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

  20. Ultrafine particles affect the balance of endogenous pro- and anti-inflammatory lipid mediators in the lung: in-vitro and in-vivo studies

    Directory of Open Access Journals (Sweden)

    Beck-Speier Ingrid

    2012-07-01

    significantly increased also one day after UfCP exposure. Immunohistochemistry localized highest concentrations of PGE2 especially in AM one day after UfCP exposure. Conclusion Our results suggest that UfCP exposure affects the balance between pro- and anti-inflammatory lipid mediators. In allergic mice, where the endogenous balance of pro- and anti-inflammatory mediators is already altered, UfCP exposure aggravates the inflammation and the increase in anti-inflammatory, pro-resolving lipid mediators is insufficient to counterbalance the extensive inflammatory response. This may be a contributing mechanism that explains the increased susceptibility of asthmatic patients towards particle exposure.

  1. Histochemical and immunohistochemical analysis of ruptured atherosclerotic abdominal aortic aneurysm wall

    Directory of Open Access Journals (Sweden)

    Tanasković Irena

    2010-01-01

    Full Text Available Background/Aim. The main complication of the atherosclerotic abdominal aortic aneurism (AAA is her rupture that begins with lesion in intima and rupture. The purpose of this work was to determine immunocytochemical and morphofunctional characteristics of the cells in aortic wall in ruptured atherosclerotic abdominal aortic aneurysm. Method. During the course of this study, 20 samples of atherosclerotic AAA were analyzed, all of them obtained during authopsy. The samples were fixed in 4% formalin and embedded in paraffin. Sections of 5 μm thickness were stained histochemically (of Heidenhain azan stain and Periodic acid Schiff - PAS stain and immunocytochemically using a DAKO LSAB+/HRP technique to identify α-smooth muscle actin (α-SMA, vimentin, myosin heavy chains (MHC, desmin, S-100 protein, CD45 and CD68 (DAKO specification. Results. The results of our study showed that ruptured atherosclerotic AAA is characterized by a complete absence of endothelial cells, the disruption of basal membrane and internal elastic lamina, as well as a presence of the remains of hypocellular complicated atherosclerotic lesion in intima. On the plaque margins, as well as in the media, smooth muscle cells (SMCs are present, which express a α-SMA and vimentin (but without MHC or desmin expression, as well as leukocyte infiltration, and a large number of foam cells. Some of the foam cells show a CD68-immunoreactivity, while the others show vimentin- and S-100 protein-immunoreactivity. Media is thinned out with a disorganized elastic lamellas, while adventitia is characterized by inflammatory inflitrate (infection. Conclusion. Rupture of aneurysm occurs from the primary intimal disruption, which spreads into thinned out media and adventitia. Rupture is caused by unstable atherom, hypocellularity, loss of contractile characteristics of smooth muscle cells in intima and media, neovascularization of the media, as well as by the activity of the macrophages in the

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Surgical treatment of penetrating atherosclerotic ulcer of the descending aorta

    Directory of Open Access Journals (Sweden)

    Kovačević Pavle

    2013-01-01

    Full Text Available Introduction. The term “penetrating atherosclerotic ulcer” (PAU of the aorta describes the condition in which ulceration of an aortic atherosclerotic lesion penetrates the internal elastic lamina into media. PAU is a high-risk lesion due to its deleterious effects on the integrity of aortic wall, with potentially fatal outcome. Case report. A patient with intensive, sharp chest pain irradiating to the back but with no signs of myocardial ischemia on an electrocardiogram was referred to our hospital. Transthoracic echocardiography showed no pathological changes of the ascending aorta. However, multislice computed tomography (CT showed an aortic ulcer with varying degree of the subadventitial hemorrhage in the region of the thoracic aorta at the level of Th 8-9. Due to imminent rupture of the penetrating aortic ulcer, the patient was promptly prepared for surgery. A 15 cm long subadventitial hematoma was found intraoperatively in the right posterolateral aspect of the descending aorta, 5 cm above the diaphragm and 7 cm below the origin of the left subclavial artery. The affected segment of the aorta was resected, followed by an inlay aortic reconstruction with a Dacron tube graft of 24 mm. Control CT revealed satisfactory reconstruction of the descending aorta. Conclusion. PAU is a rare, but potentially fatal disease. Open surgery in patients with PAU is an effective treatment strategy, although endovascular treatment options are emerging.

  4. Melatonin Does Not Affect Oxidative/Inflammatory Biomarkers in a Closed-Chest Porcine Model of Acute Myocardial Infarction

    DEFF Research Database (Denmark)

    Halladin, Natalie L.; Ekelof, Sarah; Jensen, Svend Eggert;

    2014-01-01

    Aim: To test whether melatonin reduces oxidative and inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction. Materials and Methods: Twenty pigs were randomized to receive a total dosage of 200 mg (0.4 mg/ml) of melatonin, or placebo immediately prior to reperfusion...... or oxidative stress markers after experimental myocardial infarction compared to placebo....

  5. Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study

    NARCIS (Netherlands)

    M.P.M. de Maat (Moniek); M.L. Bots (Michiel); M.M.B. Breteler (Monique); J. Meijer (John); A.J. Kiliaan (Amanda); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2002-01-01

    textabstractInflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), i

  6. Affectivity

    OpenAIRE

    Stenner, Paul; Greco, Monica

    2013-01-01

    The concept of affectivity has assumed central importance in much recent scholarship, and many in the social sciences and humanities now talk of an ‘affective turn’. The concept of affectivity at play in this ‘turn’ remains, however, somewhat vague and slippery. Starting with Silvan Tomkins’ influential theory of affect, this paper will explore the relevance of the general assumptions (or ‘utmost abstractions’) that inform thinking about affectivity. The technological and instrumentalist char...

  7. Low-dose irradiation affects expression of inflammatory markers in the heart of ApoE -/- mice.

    Directory of Open Access Journals (Sweden)

    Daniel Mathias

    Full Text Available Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min or high dose rate (150 mGy/min. The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45 and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025-0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM at 0.025-2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05-2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen and decreases (sICAM, sVCAM, sE-selectin of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and

  8. The contemporary management of intracranial atherosclerotic disease.

    Science.gov (United States)

    Leng, Xinyi; Wong, Ka Sing; Leung, Thomas W

    2016-06-01

    Intracranial atherosclerotic disease is the most common cause of cerebral vasculopathy and an important stroke etiology worldwide, with a higher prevalence in Asian, Hispanic and African ethnicities. Symptomatic intracranial atherosclerotic disease portends a recurrent stroke risk as high as 18% at one year. The key to secondary prevention is an understanding of the underlying stroke mechanism and aggressive control of conventional cardiovascular risks. Contemporary treatment includes antiplatelet therapy, optimal glycemic and blood pressure control, statin therapy and lifestyle modifications. For patients with high-grade (70-99%) symptomatic steno-occlusion, short-term dual antiplatelet therapy with aspirin and clopidogrel followed by life-long single antiplatelet therapy may reduce the recurrent risk. Current evidence does not advocate percutaneous transluminal angioplasty and stenting as an initial treatment. External counterpulsation, encephaloduroarteriosynangiosis and remote limb ischemic preconditioning are treatments under investigation. Future studies should aim at predicting patients prone to recurrence despite of medical therapies and testing the efficacy of emerging therapies.

  9. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: lifestyle changes affecting the host-environment interface.

    Science.gov (United States)

    Ehlers, S; Kaufmann, S H E

    2010-04-01

    In industrialized nations and high-income regions of the world, the decline of infectious diseases is paralleled by an increase in allergic, autoimmune and chronic inflammatory diseases (AACID). Changes in lifestyle in westernized societies, which impact individually and collectively on intestinal microbiota, may - at least in part - account for the AACID pandemic. Many disease genes that contribute to AACID encode pattern recognition and signalling molecules in barrier-associated cells. Interactions between gene products and environmental factors depend highly upon the host's state of maturation, the composition of the skin and gut microflora, and exposure to pollutants, antibiotics and nutrients. Inflammatory stress responses, if regulated appropriately, ensure immunity, health and relative longevity; when they are dysregulated, they can no longer be terminated appropriately and thus precipitate AACID. The 99th Dahlem Conference brought together experts of various disciplines (genetics, evolution biology, molecular biology, structural biology, cell biology, immunology, microbiology, nutrition science, epidemiology and clinical medicine) to discuss the multi-faceted relationships between infection, immunity and inflammation in barrier organs and the development of AACID. In Clinical and Experimental Immunology we are presenting a compilation of background papers that formed the basis of discussions. Controversial viewpoints and gaps in current knowledge were examined and new concepts for prevention and treatment of CID were formulated.

  10. Endovascular revascularization for aortoiliac atherosclerotic disease

    Science.gov (United States)

    Aggarwal, Vikas; Waldo, Stephen W; Armstrong, Ehrin J

    2016-01-01

    Atherosclerotic iliac artery disease is increasingly being treated with endovascular techniques. A number of new stent technologies can be utilized with high long-term patency, including self-expanding stents, balloon-expandable stents, and covered stents, but comparative data on these stent types and in more complex lesions are lacking. This article provides a review of currently available iliac stent technologies, as well as complex procedural aspects of iliac artery interventions, including approaches to the treatment of iliac bifurcation disease, long segment occlusions, choice of stent type, and treatment of iliac artery in-stent restenosis. PMID:27099509

  11. Mechanical model of vulnerable atherosclerotic plaque rupture

    Institute of Scientific and Technical Information of China (English)

    SU; Haijun; ZHANG; Mei; ZHANG; Yun

    2004-01-01

    Rupture of atherosclerotic plaque is the main trigger of acute cardiovascular events, but the mechanism of plaque rupture is still unknown. We have constructed a model describing the motion of the fibrous cap of the plaque using the theory of elastic mechanics and studied the stability of the plaque theoretically. It has shown that plaque rupture is the result of a dynamic interplay between factors intrinsic to the plaque itself and extrinsic factors. We have proposed a new mechanism of plaque rupture, given a new explanation about the nonlinear dynamic progress of atherosclerosis and suggested a method to identify the vulnerable plaques to manage atherosclerosis.

  12. Direct association between diet and the stability of human atherosclerotic plaque

    OpenAIRE

    Isabel Gonçalves; Elisavet Andersson Georgiadou; Sören Mattsson; Göran Skog; Luís Pedro; José Fernandes e Fernandes; Nuno Dias; Gunnar Engström; Jan Nilsson; Kristina Stenström

    2015-01-01

    Mediterranean diet has been suggested to explain why coronary heart disease mortality is lower in southern than northern Europe. Dietary habits can be revealed by isotope ratio mass spectrometry (IRMS) measurement of carbon (δ(13)C) and nitrogen (δ(15)N) in biological tissues. To study if diet is associated with human plaque stability, atherosclerotic plaques from carotid endarterectomy on 56 patients (21 Portuguese and 35 Swedish) were analysed by IRMS and histology. Plaque components affect...

  13. 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....

  14. 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.

  15. The contemporary management of intracranial atherosclerotic disease.

    Science.gov (United States)

    Leng, Xinyi; Wong, Ka Sing; Leung, Thomas W

    2016-06-01

    Intracranial atherosclerotic disease is the most common cause of cerebral vasculopathy and an important stroke etiology worldwide, with a higher prevalence in Asian, Hispanic and African ethnicities. Symptomatic intracranial atherosclerotic disease portends a recurrent stroke risk as high as 18% at one year. The key to secondary prevention is an understanding of the underlying stroke mechanism and aggressive control of conventional cardiovascular risks. Contemporary treatment includes antiplatelet therapy, optimal glycemic and blood pressure control, statin therapy and lifestyle modifications. For patients with high-grade (70-99%) symptomatic steno-occlusion, short-term dual antiplatelet therapy with aspirin and clopidogrel followed by life-long single antiplatelet therapy may reduce the recurrent risk. Current evidence does not advocate percutaneous transluminal angioplasty and stenting as an initial treatment. External counterpulsation, encephaloduroarteriosynangiosis and remote limb ischemic preconditioning are treatments under investigation. Future studies should aim at predicting patients prone to recurrence despite of medical therapies and testing the efficacy of emerging therapies. PMID:27082149

  16. Iron oxide nanoparticles surface coating and cell uptake affect biocompatibility and inflammatory responses of endothelial cells and macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Orlando, Antonina [University of Milano-Bicocca, Department of Health Sciences (Italy); Colombo, Miriam; Prosperi, Davide [University of Milano-Bicocca, Department of Biotechnology and Biosciences (Italy); Gregori, Maria; Panariti, Alice; Rivolta, Ilaria; Masserini, Massimo; Cazzaniga, Emanuela, E-mail: emanuela.cazzaniga@unimib.it [University of Milano-Bicocca, Department of Health Sciences (Italy)

    2015-09-15

    Engineered iron oxide nanoparticles (IONP) offer the possibility of a wide range of medical uses, from clinical imaging to magnetically based hyperthermia for tumor treatment. These applications require their systemic administration in vivo. An important property of nanoparticles is their stability in biological media. For this purpose, a multicomponent nanoconstruct combining high colloidal stability and improved physical properties was synthesized and characterized. IONP were coated with an amphiphilic polymer (PMA), which confers colloidal stability, and were pegylated in order to obtain the nanoconstruct PEG-IONP-PMA. The aim of this study was to utilize cultured human endothelial cells (HUVEC) and murine macrophages, taken as model of cells exposed to NP after systemic administration, to assess the biocompatibility of PEG-IONP-PMA (23.1 ± 1.4 nm) or IONP-PMA (15.6 ± 3.4 nm). PEG-IONP-PMA, tested at different concentrations as high as 20 μg mL{sup −1}, exhibited no cytotoxicity or inflammatory responses. By contrast, IONP-PMA showed a concentration-dependent increase of cytotoxicity and of TNF-α production by macrophages and NO production by HUVECs. Cell uptake analysis suggested that after PEGylation, IONP were less internalized either by macrophages or by HUVEC. These results suggest that the choice of the polymer and the chemistry of surface functionalization are a crucial feature to confer to IONP biocompatibility.

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

    Directory of Open Access Journals (Sweden)

    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

  18. Erythrocyte Duffy antigen receptor for chemokines (DARC):diagnostic and therapeutic implications in atherosclerotic Cardiovascular disease

    Institute of Scientific and Technical Information of China (English)

    Stavros APOSTOLAKIS; Georgios K CHALIKIAS; Dimitrios N TZIAKAS; Stavros KONSTANTINIDES

    2011-01-01

    Atherosclerosis is an inflammatory disease.The last three decades efforts have been made to elucidate the biochemical pathways that are implicated in the process of atherogenesis and plaque development.Chemokines are crucial mediators in every step of this process.Additionally.cellular components of the peripheral blood have been proved important mediators in the formation and progression of atherosclerotic lesions.However,until recently data were mostly focusing on leukocytes and platelets.Erythrocytes were considered unreceptive bystanders and limited data supported their importance in the progression and destabilization of the atherosclerotic plaque.Recently erythrocytes, through their Duffy antigen receptor for chemokines(DARC),have been proposed as appealing regulators of chemokine-induced pathways.Dissimilar to every other chemokine receptor DARC possesses high affinity for severalligands from both CC and CXC chemokine sub-families.Moreover,DARC is not coupled to a G-protein or any other intracellular signalling system;thus it is incapable of generating second messages.The exact biochemical role of erythrocyte DARC remains to be determined.It is however challenging the fact that DARC is a regulator of almost every CC and CXC chemokine ligand and therefore DARC antagonism could efiectively block the complex pre-inflammatory chemokine network.In the present review we intent to provid recent evidence supporting the role of erythrocytes in atherosclerosis focusing on the erythrocyte-chemokine interaction through the Duffy antigen system.

  19. Milk from different species: Relationship between protein fractions and inflammatory response in infants affected by generalized epilepsy.

    Science.gov (United States)

    Albenzio, M; Santillo, A; Ciliberti, M G; Figliola, L; Caroprese, M; Marino, R; Polito, A N

    2016-07-01

    TNF-α cytokine in the corresponding fraction. Cytokines might be useful biomarkers to discriminate the effects of foods on the inflammatory response; dietary strategies could help in alleviating the negative effects of epilepsy in infants.

  20. Milk from different species: Relationship between protein fractions and inflammatory response in infants affected by generalized epilepsy.

    Science.gov (United States)

    Albenzio, M; Santillo, A; Ciliberti, M G; Figliola, L; Caroprese, M; Marino, R; Polito, A N

    2016-07-01

    TNF-α cytokine in the corresponding fraction. Cytokines might be useful biomarkers to discriminate the effects of foods on the inflammatory response; dietary strategies could help in alleviating the negative effects of epilepsy in infants. PMID:27085400

  1. {sup 18}F-FDG in distinction of atherosclerotic plaque: Innovation in PET/MRI technology

    Energy Technology Data Exchange (ETDEWEB)

    Benedetto, Raquel; Fonseca, Lea Mirian Barbosa da, E-mail: benedettoraquel@yahoo.com.b [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Carneiro, Michel Pontes; Junqueira, Flavia Albuquerque; Coutinho Junior, Antonio [Clinica de Diagnostico por Imagem (CDPI), Rio de Janeiro, RJ (Brazil); Ristow, Arno von [Centervasc, Rio de Janeiro, RJ (Brazil)

    2009-12-15

    The glucose analogue, {sup 18}F-FDG, can be used to image inflammatory cell activity non-invasively by PET. In the present study, we investigate the possibility of using {sup 18}F-FDG to characterize atherosclerotic plaques. A 77-year-old man with symptomatic carotid atherosclerosis was imaged using {sup 18}F-FDG-PET and co-registered MRI. A plaque with intense fibrotic and necrotic content was obtained. Due to the fact that the tissue showed up as inactive, according to the metabolic activity, it was not possible to observe {sup 18}F-FDG uptake. Our aim was to confirm that it could be clinically used to predict the inflammatory activity of the plaque. (author)

  2. 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.

  3. Atherosclerotic Aortic Plaques Detected by Transesophageal Echocardiography

    Institute of Scientific and Technical Information of China (English)

    赵云; 朱文玲; 倪超; 郭丽琳; 曾勇; 方理刚

    2002-01-01

    Objective To evaluate the predictive value of atherosclerotic aortic plaques in coronary artery disease (CAD) Methods In 50patients with suspected coronary artery disease, transesophageal echocardiography was performed to examine their thoracic aortas 2 weeks before or after coronary angiography. In the cases of coronary angiography studied, stenosis of the coronary artery ≥ 50 % was considered to be due to coronary artery disease,whereas the thickness of the intima ≥ 1.3 mm was taken to be the criteria for the presence of an atherosclerotic aortic plaque on the transesophageal echocardiographic test. Results Among the 50 patients, 37 cases were diagnosed as CAD and 13 cases were considered to be normal. The plaques of the thoracic aorta were observed in 34cases in the CAD group and 3 cases in the normal group. The sensitivity and specificity of aortic plaques for CAD were 91.9 % and 76.9%, respectively. The positive and negative predictive values of the aortic plaques for CAD were 91.9% and 76.9%, respectively. The accuracy was 88.0%. 80 percent of the patients with single- yes sel disease had thoracic aortic plaques, 92 percent of the patients with two-vessel disease and 100 percent of the patients with three-vessel disease had thoracic aortic plaques. There was a significant difference in the thickness of aortic intimas between the normal group and the CAD group. Conclusions Detectingatherosclerotic plaques in the thoracic aorta with transesophageal echocardiography may be of great value in predicting the presence and extent of coronary artery disease.

  4. Lipid peroxidation-derived etheno-DNA adducts in human atherosclerotic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Jagadeesan [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); De Flora, Silvio [Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa (Italy); Izzotti, Alberto [Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa (Italy); Bartsch, Helmut [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany)]. E-mail: h.bartsch@dkfz.de

    2007-08-01

    Atherosclerosis and cancer are characterized by uncontrolled cell proliferation and share common risk factors, such as cigarette smoking, dietary habits and ageing. Growth of smooth muscle cells (SMCs) in atherosclerotic plaques may result from DNA damage, caused either by exogenous mutagens or by agents endogenously generated due to oxidative stress and lipid peroxidation (LPO). Hydroxy-2-nonenal (HNE), a major LPO product, binds covalently to cellular DNA to form the exocyclic etheno-DNA-base adducts, 1,N {sup 6}-ethenodeoxyadenine ({epsilon}dA) and 3,N {sup 4}-ethenodeoxycytosine ({epsilon}dC). By applying an ultrasensitive {sup 32}P-postlabeling-immunoaffinity method, {epsilon}dA and {epsilon}dC were quantified in abdominal aorta SMCs from 13 atherosclerotic patients and 3 non-smoking subjects without atherosclerotic lesions. The levels of etheno-adducts ranged for {epsilon}dA from 2.3 to 39.6/10{sup 8} dA and for {epsilon}dC from 10.7 to 157.7/10{sup 8} dC, with a high correlation between {epsilon}dA and {epsilon}dC (r = 0.84, P = 0.0001). Etheno-adduct levels were higher in atherosclerotic smokers than in ex-smokers for both {epsilon}dA (means 15.2 versus 7.3, P = 0.06) and {epsilon}dC (71.9 versus 51.6, not significant). {epsilon}dC levels were higher in either ex-smokers (P = 0.03) or smokers (P = 0.07) than in non-smokers. There was a poor correlation between either {epsilon}dA or {epsilon}dC and 8-hydroxy-2'-deoxyguanosine, whereas significant positive correlations were detected with the levels of several postlabeled bulky aromatic DNA adducts. In conclusion, two different types of DNA damage may be involved in atherosclerotic plaque formation and progression: (i) bulky aromatic compounds, to which aorta SMCs are chronically exposed in smokers, can either covalently bind to DNA, induce redox-cycling via quinone intermediates and/or activate local chronic inflammatory processes in the arterial wall; ii) this in turn leads to a self perpetuating

  5. Two Consecutive Days of Crossfit Training Affects Pro and Anti-inflammatory Cytokines and Osteoprotegerin without Impairments in Muscle Power.

    Science.gov (United States)

    Tibana, Ramires A; de Almeida, Leonardo M; Frade de Sousa, Nuno M; Nascimento, Dahan da Cunha; Neto, Ivo V de Sousa; de Almeida, Jeeser A; de Souza, Vinicius C; Lopes, Maria de Fátima T P L; Nobrega, Otávio de Tolêdo; Vieira, Denis C L; Navalta, James W; Prestes, Jonato

    2016-01-01

    = 0.018) as compared to pre-exercise values. Osteoprotegerin displayed a decrease 48 h following WOD 2 (~25%; p = 0.018) as compared with pre intervention. In conclusion, two consecutive Crossfit® training sessions increase pro/anti-inflammatory cytokines with no interference on muscle performance in the recovery period. PMID:27445850

  6. Two Consecutive Days of Crossfit Training Affects Pro and Anti-inflammatory Cytokines and Osteoprotegerin without Impairments in Muscle Power

    Science.gov (United States)

    Tibana, Ramires A.; de Almeida, Leonardo M.; Frade de Sousa, Nuno M.; Nascimento, Dahan da Cunha; Neto, Ivo V. de Sousa; de Almeida, Jeeser A.; de Souza, Vinicius C.; Lopes, Maria de Fátima T. P. L.; Nobrega, Otávio de Tolêdo; Vieira, Denis C. L.; Navalta, James W.; Prestes, Jonato

    2016-01-01

    = 0.018) as compared to pre-exercise values. Osteoprotegerin displayed a decrease 48 h following WOD 2 (~25%; p = 0.018) as compared with pre intervention. In conclusion, two consecutive Crossfit® training sessions increase pro/anti-inflammatory cytokines with no interference on muscle performance in the recovery period. PMID:27445850

  7. Evaluation of recombinant endostatin in the treatment of atherosclerotic plaques and neovascularization in rabbits*

    OpenAIRE

    Mao, Wei; Kong, Jing; Dai, Jin; Huang, Zhao-quan; Wang, Dong-zhi; Ni, Gui-bao; Chen, Min-Li

    2010-01-01

    Objective: Atherosclerotic plaques and neovascularization play an important role in the course of coronary atherosclerosis. This study evaluated the effect of recombinant endostatin on experimental atherosclerotic plaques and neovascularization in rabbits. Methods: Eighteen healthy male rabbits were divided into three groups: control group, atherosclerotic model group, and recombinant endostatin treated group. The atherosclerotic model was established via a high-cholesterol diet after balloon...

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

    Science.gov (United States)

    Parolini, Cinzia; Vik, Rita; Busnelli, Marco; Bjørndal, Bodil; Holm, Sverre; Brattelid, Trond; Manzini, Stefano; Ganzetti, Giulia S; Dellera, Federica; Halvorsen, Bente; Aukrust, Pål; Sirtori, Cesare R; Nordrehaug, Jan E; Skorve, Jon; Berge, Rolf K; Chiesa, Giulia

    2014-01-01

    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.

  10. Prevalence and risk factors of atherosclerotic renal artery stenosis

    Institute of Scientific and Technical Information of China (English)

    严健华

    2013-01-01

    Objective To explore the prevalence and risk factors of atherosclerotic renal artery stenosis(ARAS) in patients undergoing coronary angiography.Methods A total of 2506 patients with suspected and known coronary

  11. Atherosclerotic lesions of supra-aortic arteries in diabetic patients

    OpenAIRE

    Vidjak, Vinko; Hebrang, Andrija; Brkljačić, Boris; Brajša, Mladen; Novačić, Karlo; Barada, Ante; Škopljanac, Andrija; Erdelez, Lidija; Crnčević, Maja; Kučan, Damir; Flegar-Meštrić, Zlata; Vrhovski-Hebrang, Danijela; Roić, Goran

    2007-01-01

    The aim of this prospective study was to determine the prevalence and localization of stenotic atherosclerotic lesions of supra-aortic arteries in diabetic patients according to age and sex. Angiograms obtained by digital subtraction angiography were analyzed in 150 diabetic patients (study group) and 150 non-diabetic patients (control group) with symptoms of cerebral ischemia. Diabetic patients were found to have a significantly higher prevalence of stenotic atherosclerotic lesions ...

  12. Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity

    OpenAIRE

    Sung, Nak Yoon; Kim, Mi-Yeon; Cho, Jae Youl

    2015-01-01

    Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum i...

  13. Progression and regression of the atherosclerotic plaque.

    Science.gov (United States)

    de Feyter, P J; Vos, J; Deckers, J W

    1995-08-01

    In animals in which atherosclerosis was induced experimentally (by a high cholesterol diet) regression of the atherosclerotic lesion was demonstrated after serum cholesterol was reduced by cholesterol- lowering drugs or a low-fat diet. Whether regression of advanced coronary arterly lesions also takes place in humans after a similar intervention remains conjectural. However, several randomized studies, primarily employing lipid-lowering intervention or comprehensive changes in lifestyle, have demonstrated, using serial angiograms, that it is possible to achieve less progression, arrest or even (small) regression of atherosclerotic lesions. The lipid-lowering trials (NHBLI, CLAS, POSCH, FATS, SCOR and STARS) studied 1240 symptomatic patients, mostly men, with moderately elevated cholesterol levels and moderately severe angiographic-proven coronary artery disease. A variety of lipid-lowering drugs, in addition to a diet, were used over an intervention period ranging from 2 to 3 years. In all but one study (NHBLI), the progression of coronary atherosclerosis was less in the treated group, but regression was induced in only a few patients. The overall relative risk of progression of coronary atherosclerosis was 0 x 62 and 2 x 13, respectively. The induced angiographic differences were small and did not produce any significant haemodynamic benefit. The most important result was tht the disease process could be stabilized in the majority of patients. Three comprehensive lifestyle change trials (the Lifestyle Heart study, STARS and the Heidelberg Study) studied 183 patients, who were subjected to stress management, and/or intensive exercise, in addition to a low fat diet, over a period ranging from 1 to 3 years. All three trials demonstrated less progression, and more regression with overall relative risks of 0 x 40 and 2 x 35 respectively, in the intervention groups. Angiographic trials demonstrated that retardation or arrest of coronary atherosclerosis was possible

  14. 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.

  15. Insulin inhibits inflammation and promotes atherosclerotic plaque stability via PI3K-Akt pathway activation.

    Science.gov (United States)

    Yan, Hao; Ma, Ying; Li, Yan; Zheng, Xiaohui; Lv, Ping; Zhang, Yuan; Li, Jia; Ma, Meijuan; Zhang, Le; Li, Congye; Zhang, Rongqing; Gao, Feng; Wang, Haichang; Tao, Ling

    2016-02-01

    Toll-like receptor (TLR) 4 induced inflammation was reported to play an important role in atherosclerotic plaque stability. Recent studies indicated that insulin could inhibit inflammation by activating phosphatidylinositol 3-kinase-Akt-dependent (PI3K-Akt) signaling pathway. In the current study, we hypothesized that insulin would inhibit TLR4 induced inflammation via promoting PI3K-Akt activation, thus enhancing the stabilization of atherosclerotic plaques. In order to mimic the process of plaque formation, monocyte-macrophage lineage RAW264.7 were cultured and induced to form foam cells by oxidized LDL (ox-LDL). Oil red O staining results showed that insulin significantly restrained ox-LDL-induced foam cell formation. Analysis of inflammatory reaction during foam cell formation indicated that insulin significantly down-regulated the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 levels, inhibited TLR4, myeloid differentiation primary response gene (MyD) 88 and nuclear factor (NF)-κB. Further mechanism analysis showed that pretreating with the PI3K blocker, wortmannin dramatically dampened the insulin-induced up-regulation of pAkt expression. Additionally, blockade of PI3K-Akt signaling also dampened the immunosuppression effect brought by insulin. Following the construction of a rodent atherosclerosis model, pretreatment of insulin resulted in an evident decrease in lipid deposition of the blood vessel wall, serum levels of TNF-α and IL-6, and numbers of infiltrated macrophages and foam cells. Taken together, these results suggested that insulin might inhibit inflammation and promote atherosclerotic plaque stability via the PI3K-Akt pathway by targeting TLR4-MyD88-NF-κB signaling. Our findings may provide a potential target for the prevention of cardiovascular disease. PMID:26681144

  16. 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.

  17. Lack of macrophage migration inhibitory factor in mice does not affect hallmarks of the inflammatory/immune response during the first week after stroke

    Directory of Open Access Journals (Sweden)

    Deierborg Tomas

    2011-06-01

    Full Text Available Abstract Background Macrophage migration inhibitory factor (MIF has been proposed to play a detrimental role in stroke. We recently showed that MIF promotes neuronal death and aggravates neurological deficits during the first week after experimental stroke, in mice. Since MIF regulates tissue inflammation, we studied the putative role of MIF in post-stroke inflammation. Methods We subjected C57BL/6 mice, Mif-/- (MIF-KO or Mif+/+ (WT, to a transient occlusion of the right middle cerebral artery (tMCAo or sham-surgery. We studied MIF expression, GFAP expression and the number of CD74-positive cells in the ischemic brain hemisphere 7 days after tMCAo using primarily immunohistochemistry. We determined IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-12, KC/CXCL-1 and TNF-α protein levels in the brain (48 h after surgery and serum (48 h and 7 days after surgery by a multiplex immunoassay. Results We observed that MIF accumulates in neurons and astrocytes of the peri-infarct region, as well as in microglia/macrophages of the infarct core up to 7 days after stroke. Among the inflammatory mediators analyzed, we found a significant increase in cerebral IL-12 and KC levels after tMCAo, in comparison to sham-surgery. Importantly, the deletion of Mif did not significantly affect the levels of the cytokines evaluated, in the brain or serum. Moreover, the spleen weight 48 h and 7 days subsequent to tMCAo was similar in WT and MIF-KO mice. Finally, the extent of GFAP immunoreactivity and the number of MIF receptor (CD74-positive cells within the ischemic brain hemisphere did not differ significantly between WT and MIF-KO mice subjected to tMCAo. Conclusions We conclude that MIF does not affect major components of the inflammatory/immune response during the first week after experimental stroke. Based on present and previous evidence, we propose that the deleterious MIF-mediated effects in stroke depend primarily on an intraneuronal and/or interneuronal action.

  18. Serum adiponectin level in hypertensive patients and its association with atherosclerotic risk factors

    Directory of Open Access Journals (Sweden)

    Bülent Uygungelen

    2013-06-01

    Full Text Available Aim. Hypertension is one of the major risk factors for atherosclerosis. Adiponectin is mainly synthesized by white adipose tissue; it is known to have anti-atherogenic and anti-inflammatory effects on endothelial cells and macrophages. Methods. A total of 80 individuals including 48 hypertensive and 32 normotensive individuals were included in the study. Groups were separated as obese and non-obese. Results. It was found out that the patient group had statistically higher systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, triglyceride, low density lipoprotein, high sensitive C reactive protein and microalbuminuria values than the control group while high density lipoprotein values were significantly lower (p<0.05. When adiponectin levels of the groups were compared, the patient group had an adiponectin level of 8.66±2.75 µg/mL and the control group had an adiponectin level of 15.01±3.99 µg/mL. There was a statistically significant difference between two groups (p<0.05. There was a negative correlation between adiponectin level and atherosclerotic risk factors. Conclusion. Adiponectin level was lower in hypertensive group when compared to the control group; there was also a significant association between adiponectin and atherosclerotic risk factors. A low adiponectin level constitutes an important risk for development of atherosclerosis.

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Gold nanoparticles based imaging technique and drug delivery for the detection and treatment of atherosclerotic vascular disease

    Science.gov (United States)

    Ankri, Rinat; Leshem-Lev, Dorit; Lev, Eli I.; Motiei, Menachem; Hochhauser, Edith; Fixler, Dror

    2016-03-01

    In our study we aim to develop a new, simple and non-invasive method to detect and to treat atherosclerosis. We use gold nanoparticles (GNPs) combined with the diffusion reflection (DR) method to demonstrate the detection of vulnerable atherosclerotic plaques. Our method is based on the fact that macrophages are a major component in the vulnerable plaque and are able to uptake metal nanoparticles that can be discovered by the DR system. Moreover, it is well known that high density lipoprotein (HDL) reduces ASVD by inhibiting pro-inflammatory factors, enabling the specific treatment of atherosclerosis.

  3. Atherosclerotic Renal Artery Stenosis and Hypertension: Pragmatism, Pitfalls, and Perspectives.

    Science.gov (United States)

    Bavishi, Chirag; de Leeuw, Peter W; Messerli, Franz H

    2016-06-01

    For many years and even decades, a diagnostic work-up to look for a secondary form of hypertension, particularly of renovascular origin, has been a central tenet in medicine. Atherosclerotic renal artery stenosis is considered the most common cause of renovascular hypertension. However, advances in understanding the complex pathophysiology of this condition and the recently documented futility of renal revascularization bring into question whether atherosclerotic renal artery stenosis truly causes "renovascular hypertension." From a clinical point of view, a clear distinction should be made between hypertension associated with atherosclerotic renal artery stenosis and hypertension caused by renal artery stenosis-induced activation of the renin-angiotensin-aldosterone system. Most patients with atherosclerotic renal artery stenosis do not have a form of hypertension that is remediable or improved by angioplasty; to expose them to the cost, inconvenience, and risk of a diagnostic work-up add up to little more than a wild goose chase. However, with very few exceptions, medical therapy with antihypertensives and statins remains the cornerstone for the management of patients with atherosclerotic renal artery stenosis and hypertension. PMID:26522797

  4. Capsular warning syndrome and crescendo lacunar strokes after atherosclerotic stenosis of the recurrent artery of Heubner.

    Science.gov (United States)

    Cohen, José E; Rabinstein, Alejandro; Gomori, John M; Leker, Ronen R

    2012-12-01

    The stereotype of repetitive transient cerebral ischemia causing unilateral motor, sensory, or sensorimotor deficits that simultaneously affect the face, arm, and leg, clinically localized to the internal capsule, fits with the description of capsular warning syndrome (CWS). A high proportion of individuals with these symptoms develop subsequent capsular stroke, despite various proposed preventative measures. It has been postulated that the mechanism for such strokes is that of small-vessel single-penetrator disease. We present a patient with repetitive CWS intermingled with crescendo capsular strokes secondary to recurrent artery of Heubner disease. This report causally links CWS-crescendo lacunar strokes and Heubner artery atherosclerotic disease (intracranial branch atheromatous disease).

  5. Delivery of negatively charged liposomes into the atherosclerotic plaque of apolipoprotein E-deficient mouse aortic tissue.

    Science.gov (United States)

    Zhaorigetu, Siqin; Rodriguez-Aguayo, Cristian; Sood, Anil K; Lopez-Berestein, Gabriel; Walton, Brian L

    2014-09-01

    Liposomes have been used to diagnose and treat cancer and, to a lesser extent, cardiovascular disease. We previously showed the uptake of anionic liposomes into the atheromas of Watanabe heritable hyperlipidemic rabbits within lipid pools. However, the cellular distribution of anionic liposomes in atherosclerotic plaque remains undescribed. In addition, how anionic liposomes are absorbed into atherosclerotic plaque is unclear. We investigated the uptake and distribution of anionic liposomes in atherosclerotic plaque in aortic tissues from apolipoprotein E-deficient (ApoE(-/-)) mice. To facilitate the tracking of liposomes, we used liposomes containing fluorescently labeled non-silencing small interfering RNA. Confocal microscopy analysis showed the uptake of anionic liposomes into atherosclerotic plaque and colocalization with macrophages. Transmission electron microscopy analysis revealed anionic liposomal accumulation in macrophages. To investigate how anionic liposomes cross the local endothelial barrier, we examined the role of clathrin-mediated endocytosis in human coronary artery endothelial cells (HCAECs) treated with or without the inflammatory cytokine tumor necrosis factor (TNF)-α. Pretreatment with amantadine, an inhibitor of clathrin-mediated endocytosis, significantly decreased liposomal uptake in HCAECs treated with or without TNF-α by 77% and 46%, respectively. Immunoblot analysis showed that endogenous clathrin expression was significantly increased in HCAECs stimulated with TNF-α but was inhibited by amantadine. These studies indicated that clathrin-mediated endocytosis is partly responsible for the uptake of liposomes by endothelial cells. Our results suggest that anionic liposomes target macrophage-rich areas of vulnerable plaque in ApoE(-)(/)(-) mice; this finding may lead to the development of novel diagnostic and therapeutic strategies for treating vulnerable plaque in humans.

  6. Value of detection of atherosclerotic lesions using autologous labelled platelets

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    Sinzinger, H.; Silberbauer, K.; Fitscha, P.; Kaliman, J. (Vienna Univ. (Austria). 2. Medizinische Klinik; Vienna Univ. (Austria). Kardiologische Abt.; Allgem. Poliklinik, Vienna (Austria). 2. Medizinische Abteilung)

    1982-01-01

    In 44 patients with clinical signs of carotid artery stenosis a positive Doppler-ultrasound was obtained. In all patients the lesions were confirmed by angiography. In the patients labelling of autologous platelets with 111 Indium-oxine-sulphate was done in order to calculate the platelet half-life. In addition we tried to visualize the verified atherosclerotic lesions under a gamma-camera. In all patients the platelet half-life was significantly shortened in comparison to the controls. In none of the patients studied a visualization of the angiographically verified atherosclerotic lesions could be obtained. These findings point out, that only in recently developed and very severe atherosclerotic lesions the number of platelets deposed on the vascular surface is enough to allow gamma-camera imaging.

  7. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis.

    Science.gov (United States)

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-12-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  8. Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats.

    Science.gov (United States)

    Goswami, Ananda Raj; Dutta, Goutam; Ghosh, Tusharkanti

    2016-06-01

    Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS. PMID:26894935

  9. The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

    Directory of Open Access Journals (Sweden)

    Natalia P. Machado

    2013-09-01

    Full Text Available OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%, parasitic (23.5%, fungal (20.6% and viral (8.8% agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab.

  10. Systemic effects of periodontitis: lessons learned from research on atherosclerotic vascular disease and adverse pregnancy outcomes.

    Science.gov (United States)

    Papapanou, Panos N

    2015-12-01

    Studies conducted over the past 25 years have focussed on the role of periodontitis, an inflammatory condition of microbial aetiology that destroys the tooth-supporting tissues, as a systemic inflammatory stressor that can act as an independent risk factor of atherosclerotic vascular disease (AVSD) and adverse pregnancy outcomes (APOs). It has been suggested that periodontitis-associated bacteraemias and systemic dissemination of inflammatory mediators produced in the periodontal tissues may result in systemic inflammation and endothelial dysfunction, and that bacteria of oral origin may translocate into the feto-placental unit. Epidemiological studies largely support an association between periodontitis and ASVD/APOs, independently of known confounders; indeed, periodontitis has been shown to confer statistically significantly elevated risk for clinical events associated with ASVD and APOs in multivariable adjustments. On the other hand, intervention studies demonstrate that although periodontal therapy reduces systemic inflammation and improves endothelial function, it has no positive effect on the incidence of APOs. Studies of the effects of periodontal interventions on ASVD-related clinical events are lacking. This review summarises key findings from mechanistic, association and intervention studies and attempts to reconcile the seemingly contradictory evidence that originates from different lines of investigation.

  11. Increased metabolite levels of glycolysis and pentose phosphate pathway in rabbit atherosclerotic arteries and hypoxic macrophage.

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    Atsushi Yamashita

    Full Text Available AIMS: Inflammation and possibly hypoxia largely affect glucose utilization in atherosclerotic arteries, which could alter many metabolic systems. However, metabolic changes in atherosclerotic plaques remain unknown. The present study aims to identify changes in metabolic systems relative to glucose uptake and hypoxia in rabbit atherosclerotic arteries and cultured macrophages. METHODS: Macrophage-rich or smooth muscle cell (SMC-rich neointima was created by balloon injury in the iliac-femoral arteries of rabbits fed with a 0.5% cholesterol diet or a conventional diet. THP-1 macrophages stimulated with lipopolysaccharides (LPS and interferon-γ (INFγ were cultured under normoxic and hypoxic conditions. We evaluated comprehensive arterial and macrophage metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using (18F-fluorodeoxyglucose ((18F-FDG and pimonidazole, a marker of hypoxia. RESULTS: The levels of many metabolites increased in the iliac-femoral arteries with macrophage-rich neointima, compared with those that were not injured and those with SMC-rich neointima (glycolysis, 4 of 9; pentose phosphate pathway, 4 of 6; tricarboxylic acid cycle, 4 of 6; nucleotides, 10 of 20. The uptake of (18F-FDG in arterial walls measured by autoradiography positively correlated with macrophage- and pimonidazole-immunopositive areas (r = 0.76, and r = 0.59 respectively; n = 69 for both; p<0.0001. Pimonidazole immunoreactivity was closely localized with the nuclear translocation of hypoxia inducible factor-1α and hexokinase II expression in macrophage-rich neointima. The levels of glycolytic (8 of 8 and pentose phosphate pathway (4 of 6 metabolites increased in LPS and INFγ stimulated macrophages under hypoxic but not normoxic condition. Plasminogen activator inhibitor-1 protein levels in the supernatant were closely

  12. Clinical analysis of 132 patients with atherosclerotic renal artery stenosis

    Institute of Scientific and Technical Information of China (English)

    徐红

    2006-01-01

    Objective To evaluate the prognostic result of renal function on atherosclerotic renal artery stenosis (ARAS) patients after revascularization and medication therapy. Methods The clinical data of 132 AEIAS patients diagnosed by renal angiography were analysed. For comparing the differences of glomenilar filtration rate (GFR) be-

  13. ATHEROSCLEROTIC CARDIOVASCULAR DISEASE IN OLDER ADULTS WITH DIABETES MELLITUS

    OpenAIRE

    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.

  14. 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.

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

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    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.

  16. Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice.

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    Mathieu Darsigny

    Full Text Available BACKGROUND: Hnf4alpha, an epithelial specific transcriptional regulator, is decreased in inflammatory bowel disease and protects against chemically-induced colitis in mice. However, the precise role of this factor in maintaining normal inflammatory homeostasis of the intestine remains unclear. The aim of this study was to evaluate the sole role of epithelial Hnf4alpha in the maintenance of gut inflammatory homeostasis in mice. METHODOLOGY/PRINCIPAL FINDINGS: We show here that specific epithelial deletion of Hnf4alpha in mice causes spontaneous chronic intestinal inflammation leading to focal areas of crypt dropout, increased cytokines and chemokines secretion, immune cell infiltrates and crypt hyperplasia. A gene profiling analysis in diseased Hnf4alpha null colon confirms profound genetic changes in cell death and proliferative behaviour related to cancer. Among the genes involved in the immune protection through epithelial barrier function, we identify the ion transporter claudin-15 to be down-modulated early in the colon of Hnf4alpha mutants. This coincides with a significant decrease of mucosal ion transport but not of barrier permeability in young animals prior to the manifestation of the disease. We confirm that claudin-15 is a direct Hnf4alpha gene target in the intestinal epithelial context and is down-modulated in mouse experimental colitis and inflammatory bowel disease. CONCLUSION: Our results highlight the critical role of Hnf4alpha to maintain intestinal inflammatory homeostasis during mouse adult life and uncover a novel function for Hnf4alpha in the regulation of claudin-15 expression. This establishes Hnf4alpha as a mediator of ion epithelial transport, an important process for the maintenance of gut inflammatory homeostasis.

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

    Directory of Open Access Journals (Sweden)

    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

  18. Leukotriene B4 levels in human atherosclerotic plaques and abdominal aortic aneurysms.

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    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

  19. Notoginsenoside R1 attenuates atherosclerotic lesions in ApoE deficient mouse model.

    Directory of Open Access Journals (Sweden)

    Chenglin Jia

    Full Text Available AIMS: Atherosclerosis is the primary cause of cardiovascular diseases and stroke. The current study evaluated the interventional effects of a naturally occurring compound Notoginsenoside R1 (NR1 on atherosclerosis in ApoE-/- mice. METHODS AND RESULTS: The atherosclerotic lesion was significantly alleviated by NR1 treatment and this attenuation was marked by reduction in lipid deposition, fibrosis and oxidative stress. Increased serum levels of GSH and SOD and decreased level of MDH were observed in NR1-treated ApoE-/- mice. NR1 treatment also significantly decreased the levels of CHO, TG, ox-LDL and increased the level of HDL. Additionally, the levels of inflammatory cytokines including IL-2, IL-6, TNF-α and γ-IFN were markedly reduced in NR1-treated ApoE-/- mice. Furthermore, significantly increased aortic expression of miR-26a, miR-21, miR-126a, miR-132, miR-146 and miR-155 and decreased expression of miR-20a and miR-92a were observed in the vehicle-treated ApoE-/- mice. While NR1 treatment led to a significant reduction in the expression of miR-21, miR-26a, miR-126 and increased expression of miR-20a. CONCLUSION: Collectively, our results demonstrated for the first time the anti-atherosclerotic effects of NR1, which could be in part mediated through its multiple targeting effects on inflammation, oxidative stress, lipid metabolism and microRNA expression. These results therefore justify further evaluation of NR1 as a therapeutic agent treating atherosclerosis.

  20. Relationship between interleukin-18 levels and characterization of atherosclerotic plaque and percutaneous coronary intervention

    Institute of Scientific and Technical Information of China (English)

    Weihua Li; Kaimin Lin; Lei Gao; Rong Wu; Qiang Xie; Yongjun Guo; Shuhui Dai

    2008-01-01

    Background lnterleuldn-18(IL- 18) plays a key role in the development,progression and outcome of coronary artery disease and its complications.However,its variability relation to the characterization of atherosclerotic plaque and percutaneous coronary intervention are still unknown.Methods Fifty four patients with coronary artery disease [22 patients with stable angina (SA) and 32 patients with acute coronary syndrome (ACS)] were enrolled in this study.All patients underwent percutaneous coronary intervention (PCI).The stability of the plaques at the criminal vessels was assessed with analogical IVUS.Serum IL-18 levels were measured at the time points of 5 rain before PCI,and Oh,6h,24h and lmonth after PCI in all patients.Results ACS group consisted mainly of lipidic unstable plaques while SA group of fibrous stable plaques.Moreover,compared with those in SA group,eccentricity index (EI) and remodeling index (RI) were significantly higher in ACS group.Positive remodeling was seen in ACS group while negative or no remodeling in SA group.Further,serum IL-18 levels were significantly elevated in patients with ACS than those in SA group before PCI,increased at Oh,6h,24h after PCI (P<0.05)and were not significant different at 1 month after PCI from those before PCI.Conclusions There is significant difference in the composition and structural characteristics of atherosclerotic plaques between ACS and UA groups.PCI triggersd and enhances the inflammatory response in a short time.Serum levels of IL- 18 are the predictors of progression of unstable plaque in atherosclerosis.Post-operative complications of PCI might be reduced by inhibiting IL- 18.(J Geriatr Cardiol 2008;5:21-24)

  1. Oral P. gingivalis infection alters the vascular reactivity in healthy and spontaneously atherosclerotic mice

    Directory of Open Access Journals (Sweden)

    Stefanon Ivanita

    2011-05-01

    Full Text Available Abstract Background Considering that recent studies have demonstrated endothelial dysfunction in subjects with periodontitis and that there is no information about vascular function in coexistence of periodontitis and atherosclerosis, we assessed the impact of oral inoculation with the periodontal pathogen Porphyromonas gingivalis on vascular reactivity in healthy and hypercholesterolemic apolipoprotein E-deficient (ApoE mice. In vitro preparations of mesenteric arteriolar bed were used to determine the vascular responses to acetylcholine, sodium nitroprusside and phenylephrine (PE. Results Alveolar bone resorption, an evidence of periodontitis, was assessed and confirmed in all infected mice. Acetylcholine- and sodium nitroprusside-induced vasorelaxations were similar among all groups. Non-infected ApoE mice were hyperreactive to PE when compared to non-infected healthy mice. P gingivalis infection significantly enhanced the vasoconstriction to PE in both healthy and spontaneous atherosclerotic mice, when compared to their respective controls. Conclusions This study demonstrates that oral P gingivalis affects the alpha-adrenoceptor-mediated vascular responsiveness in both healthy and spontaneous atherosclerotic mice, reinforcing the association between periodontitis and cardiovascular diseases.

  2. Epigenetic Modulation in the treatment Atherosclerotic disease

    Directory of Open Access Journals (Sweden)

    Mikaela M Byrne

    2014-10-01

    Full Text Available Cardiovascular disease is the single largest cause of death in the western world and its incidence is on the rise globally. Atherosclerosis, characterised by the development of atheromatus plaque, can trigger luminal narrowing and upon rupture result in myocardial infarction or ischemic stroke. Epigenetic mechanisms are a source of considerable research interest due to the role they play in gene regulation. Epigenetic mechanisms such as DNA methylation and histone acetylation have been identified as potential drug targets in the treatment of cardiovascular disease. miRNAs are known to play a role in gene silencing, which has been widely investigated in cancer. In comparison, the role they play in cardiovascular disease and plaque rupture is not well understood. Nutritional epigenetic modifiers from dietary components, for instance sulforaphane found in broccoli, have been shown to suppress the pro-inflammatory response through transcription factor activation. This review will discuss current and potential epigenetic therapeutics for the treatment of cardiovascular disease, focusing on the use of miRNAs and dietary supplements such as sulforaphane and protocatechuic aldehyde.

  3. 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. PMID:26777261

  4. Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion

    Institute of Scientific and Technical Information of China (English)

    Fang Huang; Hongwen He; Wenguo Fan; Yongliang Liu; Hongyu Zhou; Bin Cheng

    2013-01-01

    Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin re-ceptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal minal nucleus and trigeminal ganglion was determined with immunohistochemistry and mistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings sug-gest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin’s regulatory effect on pain is attenuated.

  5. Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice.

    Science.gov (United States)

    Gómez-Hernández, Almudena; Beneit, Nuria; Escribano, Óscar; Díaz-Castroverde, Sabela; García-Gómez, Gema; Fernández, Silvia; Benito, Manuel

    2016-09-01

    Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE(-/-) mice showed greater hypertriglyceridemia than the obtained in ApoE(-/-) and hypercholesterolemia similar to ApoE(-/-) mice. BATIRKO;ApoE(-/-) mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-α and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations. PMID:27414981

  6. Human urotensin II promotes hypertension and atherosclerotic cardiovascular diseases.

    Science.gov (United States)

    Watanabe, Takuya; Arita, Shigeko; Shiraishi, Yuji; Suguro, Toshiaki; Sakai, Tetsuo; Hongo, Shigeki; Miyazaki, Akira

    2009-01-01

    Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population. Plasma U-II levels are elevated in patients with vascular endothelial dysfunction-related diseases such as essential hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. Chronic infusion of U-II enhances atherosclerotic lesions in the aorta in apolipoprotein E-knockout mice. In human atherosclerotic plaques from the aorta and coronary and carotid arteries, U-II is expressed at high levels in endothelial cells (ECs) and lymphocytes, whereas UT is expressed at high levels in vascular smooth muscle cells (VSMCs), ECs, monocytes, and macrophages. U-II stimulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in human ECs as chemoattractant for monocytes, and accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. U-II produces reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate oxidase activation in human VSMCs, and stimulates VSMC proliferation with synergistic effects when combined with ROS, oxidized LDL, and serotonin. Clinical studies demonstrated increased plasma U-II levels in accordance with the severity of carotid atherosclerosis in patients with essential hypertension and that of coronary artery lesions in patients with ischemic heart disease. Here, we summarize the key roles of U-II in progression of hypertension and atherosclerotic cardiovascular diseases

  7. High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

    Science.gov (United States)

    Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

    2016-02-01

    Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

  8. 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.)

  9. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    International Nuclear Information System (INIS)

    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.)

  10. 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

  11. 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.

  12. Blocking TLR2 activity diminishes and stabilizes advanced atherosclerotic lesions in apolipoprotein E-deficient mice

    Institute of Scientific and Technical Information of China (English)

    Xiao-xing WANG; Xiao-xi LV; Jia-ping WANG; Hui-min YAN; Zi-yan WANG; Han-zhi LIU; Xiao-ming FU

    2013-01-01

    Aim:Toll-like receptor 2 (TLR2) signaling plays a critical role in the initiation of atherosclerosis.The aim of this study was to investigate whether blocking TLR2 activity could produce therapeutic effects on advanced atherosclerosis.Methods:Forty-week old apolipoprotein E-deficient (ApoE-/-) mice fed on a normal diet were intravenously injected with a TLR2-neutralizing antibody or with an isotype-matched IgG for 18 weeks.Double-knockout ApoE-/-Tlr2-/-mice were taken as a positive control.At the end of the treatments,the plasma lipid levels were measured,and the plaque morphology,pro-inflammatory cytokines expression and apoptosis in arteries were analyzed.In the second part of this study,6-week old ApoE-/-and ApoE-/-Tlr2-/-mice fed on a high-cholesterol diet for 12 to 24 weeks,the expression levels of TLR2 and apoptotic markers in arteries were examined.Results:Blockade of TLR2 activity with TLR2-neutralizing antibody or knockout of Tlr2 gene did not alter the plasma lipid levels in ApoE-/-mice.However,the pharmacologic and genetic manipulations significantly reduced the plaque size and vessel stenosis,and increased plaque stability in the brachiocephalic arteries.The protective effects of TLR2 antagonism were associated with the suppressed expression of pro-inflammatory cytokines IL-6 and TNF-α and the inactivation of transcription factors NF-KB and Stat3.In addition,blocking TLR2 activity attenuated ER stress-induced macrophage apoptosis in the brachiocephalic arteries,which could promote the resolution of necrotic cores in advanced atherosclerosis.Moreover,high-cholesterol diet more prominently accelerated atherosclerotic formation and increased the expression of pro-apoptotic protein CHOP and apoptosis in ApoE-/-mice than in ApoE-/-Tlr2-/-mice.Conclusion:The pharmacologic or genetic blockade of TLR2 activity diminishes and stabilizes advanced atherosclerotic lesions in ApoE-/-mice.Thus,targeting TLR2 signaling may be a promising therapeutic strategy against

  13. Cannabinoids and atherosclerotic coronary heart disease.

    Science.gov (United States)

    Singla, Sandeep; Sachdeva, Rajesh; Mehta, Jawahar L

    2012-06-01

    Marijuana is the most abused recreational drug in the United States. Cannabinoids, the active ingredients of marijuana, affect multiple organ systems in the human body. The pharmacologic effects of marijuana, based on stimulation of cannabinoid receptors CB1 and CB2, which are widely distributed in the cardiovascular system, have been well described. Activation of these receptors modulates the function of various cellular elements of the vessel wall, and may contribute to the pathogenesis of atherosclerosis. Clinically, there are reports linking marijuana smoking to the precipitation of angina and acute coronary syndromes. Recently, large published clinical trials with CB1 antagonist rimonabant did not show any significant benefit of this agent in preventing progression of atherosclerosis. In light of these findings and emerging data on multiple pathways linking cannabinoids to atherosclerosis, we discuss the literature on the role of cannabinoids in the pathophysiology of atherosclerosis. We also propose a marijuana paradox, which implies that inhalation of marijuana may be linked to precipitation of acute coronary syndromes, but modulation of the endocannabinoid system by a noninhalation route may have a salutary effect on the development of atherosclerosis. PMID:22278660

  14. Androgen therapy and atherosclerotic cardiovascular disease

    Directory of Open Access Journals (Sweden)

    K-CY McGrath

    2008-02-01

    Full Text Available K-CY McGrath1, LS McRobb1,2, AK Heather1,21Heart Research Institute, Camperdown, NSW, Australia; 2Discipline of Medicine, University of Sydney, Sydney, NSW, AustraliaAbstract: Cardiovascular disease (CVD remains the leading cause of death in Western society today. There is a striking gender difference in CVD with men predisposed to earlier onset and more severe disease. Following the recent reevaluation and ongoing debate regarding the estrogen protection hypothesis, and given that androgen use and abuse is increasing in our society, the alternate view that androgens may promote CVD in men is assuming increasing importance. Whether androgens adversely affect CVD in either men or women remains a contentious issue within both the cardiovascular and endocrinological fraternities. This review draws from basic science, animal and clinical studies to outline our current understanding regarding androgen effects on atherosclerosis, the major CVD, and asks where future directions of atherosclerosis-related androgen research may lie.

  15. Activation of sterol regulatory element binding protein and NLRP3 inflammasome in atherosclerotic lesion development in diabetic pigs.

    Directory of Open Access Journals (Sweden)

    Yu Li

    Full Text Available BACKGROUND: Aberrantly elevated sterol regulatory element binding protein (SREBP, the lipogenic transcription factor, contributes to the development of fatty liver and insulin resistance in animals. Our recent studies have discovered that AMP-activated protein kinase (AMPK phosphorylates SREBP at Ser-327 and inhibits its activity, represses SREBP-dependent lipogenesis, and thereby ameliorates hepatic steatosis and atherosclerosis in insulin-resistant LDLR(-/- mice. Chronic inflammation and activation of NLRP3 inflammasome have been implicated in atherosclerosis and fatty liver disease. However, whether SREBP is involved in vascular lipid accumulation and inflammation in atherosclerosis remains largely unknown. PRINCIPAL FINDINGS: The preclinical study with aortic pouch biopsy specimens from humans with atherosclerosis and diabetes shows intense immunostaining for SREBP-1 and the inflammatory marker VCAM-1 in atherosclerotic plaques. The cleavage processing of SREBP-1 and -2 and expression of their target genes are increased in the well-established porcine model of diabetes and atherosclerosis, which develops human-like, complex atherosclerotic plaques. Immunostaining analysis indicates an elevation in SREBP-1 that is primarily localized in endothelial cells and in infiltrated macrophages within fatty streaks, fibrous caps with necrotic cores, and cholesterol crystals in advanced lesions. Moreover, concomitant suppression of NAD-dependent deacetylase SIRT1 and AMPK is observed in atherosclerotic pigs, which leads to the proteolytic activation of SREBP-1 by diminishing the deacetylation and Ser-372 phosphorylation of SREBP-1. Aberrantly elevated NLRP3 inflammasome markers are evidenced by increased expression of inflammasome components including NLPR3, ASC, and IL-1β. The increase in SREBP-1 activity and IL-1β production in lesions is associated with vascular inflammation and endothelial dysfunction in atherosclerotic pig aorta, as demonstrated

  16. Trends and Factors Affecting Hospitalization Costs in Patients with Inflammatory Bowel Disease: A Two-Center Study over the Past Decade

    Directory of Open Access Journals (Sweden)

    Junjie Xu

    2013-01-01

    Full Text Available With the growing number of patients with inflammatory bowel disease (IBD and hospitalization cases, the overall medical care cost elevates significantly in consequence. A total of 2458 hospitalizations, involving 1401 patients with IBD, were included from two large medical centers. Hospitalization costs and factors impacting cost changes were determined. Patients with IBD and frequency of hospitalizations increased significantly from 2003 to 2011 (P<0.001. The annual hospitalization cost per patient, cost per hospitalization, and daily cost during hospitalization increased significantly in the past decade (all P<0.001. However, length of stay decreased significantly (P<0.001. Infliximab was the most significant factor associated with higher hospitalization cost (OR = 44380.09, P<0.001. Length of stay (OR = 1.29, P<0.001, no medical insurance (OR = 1.31, P=0.017, CD (OR = 3.55, P<0.001, inflammatory bowel disease unclassified (IBDU (OR = 4.30, P<0.0001, poor prognosis (OR = 6.78, P<0.001, surgery (OR = 3.16, P<0.001, and endoscopy (OR = 2.44, P<0.001 were found to be predictors of higher hospitalization costs. Patients with IBD and frequency of hospitalizations increased over the past decade. CD patients displayed a special one peak for age at diagnosis, which was different from UC patients. The increased hospitalization costs of IBD patients may be associated with infliximab, length of stay, medical insurance, subtypes of IBD, prognosis, surgery, and endoscopy.

  17. Inflammatory Regulation Effect and Action Mechanism of Anti-Inflammatory Effective Parts of Housefly (Musca domestica Larvae on Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Fu Jiang Chu

    2013-01-01

    Full Text Available The protein-enriched extracts of housefly larvae were segregated by gel-filtration chromatography (GFC and then anti-inflammatory activity screening in RAW264.7 (induced by LPS was carried out. After acquire the anti-inflammatory effective parts, its anti-atherosclerotic properties in vivo were then evaluated. Results showed that the anti-inflammatory effective parts of housefly larvae were low-molecular-weight parts. After treated with the effective parts oral gavaged for 4 weeks, the atherosclerotic lesions of the mouse were significantly decreased. The inflammatory and lipid parameters were also reduced (except HDL which was increased. Western blot analysis demonstrated that the effective parts exerted potent inhibitory effect on expression of p65 in nucleus and cytoplasm. The results of immunofluorescence microscopy analysis also showed that the expressions of p65 both in cytoplasm and nucleus were significantly reduced. The hypothesis that the anti-inflammatory effective parts of housefly larvae possessed anti-atherosclerosis activity in mouse and the possible mechanism could be associated with the inhibition of expression and nuclear transfer of NF-κB p65 could be derived.

  18. Inflammatory Regulation Effect and Action Mechanism of Anti-Inflammatory Effective Parts of Housefly (Musca domestica) Larvae on Atherosclerosis.

    Science.gov (United States)

    Chu, Fu Jiang; Jin, Xiao Bao; Xu, Yin Ye; Ma, Yan; Li, Xiao Bo; Lu, Xue Mei; Liu, Wen Bin; Zhu, Jia Yong

    2013-01-01

    The protein-enriched extracts of housefly larvae were segregated by gel-filtration chromatography (GFC) and then anti-inflammatory activity screening in RAW264.7 (induced by LPS) was carried out. After acquire the anti-inflammatory effective parts, its anti-atherosclerotic properties in vivo were then evaluated. Results showed that the anti-inflammatory effective parts of housefly larvae were low-molecular-weight parts. After treated with the effective parts oral gavaged for 4 weeks, the atherosclerotic lesions of the mouse were significantly decreased. The inflammatory and lipid parameters were also reduced (except HDL which was increased). Western blot analysis demonstrated that the effective parts exerted potent inhibitory effect on expression of p65 in nucleus and cytoplasm. The results of immunofluorescence microscopy analysis also showed that the expressions of p65 both in cytoplasm and nucleus were significantly reduced. The hypothesis that the anti-inflammatory effective parts of housefly larvae possessed anti-atherosclerosis activity in mouse and the possible mechanism could be associated with the inhibition of expression and nuclear transfer of NF- κ B p65 could be derived. PMID:23554828

  19. 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 p

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

    Directory of Open Access Journals (Sweden)

    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.

  1. An uncommon cause of chest pain - penetrating atherosclerotic aortic ulcer

    OpenAIRE

    Kyaw, Htoo; Sadiq, Sanah; Chowdhury, Arnab; Gholamrezaee, Rashin; Yoe, Linus

    2016-01-01

    Chest pain is a very common symptom and can be of cardiac or non-cardiac origin. It accounts for approximately 5.5 million annual emergency room visits in the United States, according to 2011 CDC data. Penetrating atherosclerotic aortic ulcer (PAU), an uncommon condition, is also a potential cause of chest pain. We here report the case of a 65-year-old woman who presented with atypical chest and back pain. The pain persisted for 4 weeks necessitating two emergency room visits. Initial tests w...

  2. 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.

  3. ADIPONECTIN LEVELS AND ATHEROSCLEROTIC RISK FACTORS IN CHILDREN ON HEMODIALYSIS

    International Nuclear Information System (INIS)

    Atherosclerotic cardiovascular disease (ACVD) is the major cause of mortality in patients with end stage renal disease (ESRD) treated with hemodialysis (HD), even in children. Adiponectin (ADPN) is an adipocyte derived plasma protein having anti-atherogenic properties. ADPN levels are elevated in ESRD but it has been reported that ESRD patients with low plasma ADPN levels have a high risk of cardiovascular death. The aim of this study is to evaluate the relation between ADPN and atherosclerotic risk factors in children on hemodialysis.Twenty-eight children (17 boys and 11girls) with a mean age of 10.6 ± 3.34 years undergoing hemodialysis (HD) for a mean period of 11.96 ± 8.32 months (ranged from 6 to 36 months) and 10 healthy age and sex matched control subjects were enrolled in this study. The acute effect of a hemodialysis session on serum ADPN and other atherosclerotic risk factors , including blood pressure, serum lipids, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were assessed by comparison of pre- and post-hemodialysis determinations. Serum levels of ADPN and TNF-α were measured by enzyme linked immunosorbant assay (ELISA) while CRP was measured by the semi-quantitative latex agglutination assay.The data showed that serum ADPN levels were twice higher in the HD group as compared to the control subjects. Concerning the atherosclerotic risk factors, TNF-α, CRP and triglycerides levels showed significant elevation in the HD group. Meanwhile, serum albumin, cholesterol and phosphorus levels showed significant decreases. The linear regression analysis showed that adiponectin was negatively correlated with glomerular filtration rate (GFR) (r = -0.68,P < 0.0001), and body mass index (r = -0.73, P < 0.0007); ADPN levels are directly related to HDL cholesterol levels (r = 0.76, P < 0.0001) and inversely related to triglycerides level (r = -0.63, P < 0.0003). No relationship was found between adiponectin and CRP.It could be concluded that

  4. Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development

    Science.gov (United States)

    Wilensky, Robert L; Shi, Yi; Mohler, Emile R; Hamamdzic, Damir; Burgert, Mark E; Li, Jun; Postle, Anthony; Fenning, Robert S; Bollinger, James G; Hoffman, Bryan E; Pelchovitz, Daniel J; Yang, Jisheng; Mirabile, Rosanna C; Webb, Christine L; Zhang, LeFeng; Zhang, Ping; Gelb, Michael H; Walker, Max C; Zalewski, Andrew; Macphee, Colin H

    2010-01-01

    Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is associated with increased risk of cardiac events, but it is not known whether Lp-PLA2 is a causative agent. Here we show that selective inhibition of Lp-PLA2 with darapladib reduced development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic swine. Darapladib markedly inhibited plasma and lesion Lp-PLA2 activity and reduced lesion lysophosphatidylcholine content. Analysis of coronary gene expression showed that darapladib exerted a general anti-inflammatory action, substantially reducing the expression of 24 genes associated with macrophage and T lymphocyte functioning. Darapladib treatment resulted in a considerable decrease in plaque area and, notably, a markedly reduced necrotic core area and reduced medial destruction, resulting in fewer lesions with an unstable phenotype. These data show that selective inhibition of Lp-PLA2 inhibits progression to advanced coronary atherosclerotic lesions and confirms a crucial role of vascular inflammation independent from hypercholesterolemia in the development of lesions implicated in the pathogenesis of myocardial infarction and stroke. PMID:18806801

  5. The synergistic effect of antiglycating agents (MB-92) on inhibition of protein glycation, misfolding and diabetic complications in diabetic-atherosclerotic rat.

    Science.gov (United States)

    Mahdavifard, S; Bathaie, S Z; Nakhjavani, M; Taghikhani, M

    2016-10-01

    Protein glycation due to hyperglycemia resulting in misfolding and aggregation, which is known as one of the most important reasons of diabetes complications. We previously showed the beneficial effects of some antiglycating agents in diabetic rats. Here, the effect of MB-92, a combination of some amino acids and crocetin (Crt, a saffron carotenoid), was studied in the prevention of diabetic complications in diabetic-atherosclerotic rats. In addition, the inhibitory effect of these treatments on glycation intermediates, aggregation and misfolding of proteins was investigated both in vivo and in vitro. Thus, the streptozotocin-induced diabetic rats that underwent an atherogenic diet were treated with Crt, N-acetylcyctein and MB-92. Then, glycated products and markers of oxidation and inflammation, in addition to other markers of diabetes complications were studied. The results of the in vivo study indicated that the mentioned treatments prevented the atheromatos formation, reduced the increased blood glucose; inhibited the formation of various glycation products, induced glyoxalase system (I and II), diminished oxidation and inflammatory markers, and improved lipid profile and atherosclerotic index in the diabetic-atherosclerotic rats; but MB-92 was the most effective treatment. In vitro results also confirmed that MB-92 was the most effective treatment to inhibit protein glycation and misfolding in comparison with the other treatments. In conclusion, MB-92 showed the greatest potential for inhibition of glycation and oxidation products, atheromatose plaque formation and inflammation in diabetic-atherosclerotic rats, and to control protein glycation, misfolding and aggregation in high glucose concentration; thus, it can be suggested as a new drug to prevent diabetic complications. PMID:26733359

  6. Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin.

    Directory of Open Access Journals (Sweden)

    Chunmei Qi

    Full Text Available Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA modified ultra-small super paramagnetic iron oxide (USPIO was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI.Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30. Group A with atherosclerosis plaque (n = 10 were controls. VP was established in groups B (n = 10 and C (n = 10 using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured.DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05.After successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.

  7. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    Science.gov (United States)

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. PMID:27616885

  8. PEG modification on 111In-labeled phosphatidyl serine liposomes for imaging of atherosclerotic plaques

    International Nuclear Information System (INIS)

    Introduction: Previously, we reported a probe for imaging of atherosclerotic plaques: 111In-labeled liposomes. Liposomes were modified with phosphatidylserine (PS) because macrophages recognize PS and phagocytize apoptotic cells in plaques. PS modification was successful and we could visualize atherosclerotic plaques by single-photon emission computed tomography (SPECT). However, too-rapid blood clearance reduced accumulation of PS-liposomes in plaques in vivo. Therefore, in the present study, PS-liposomes were modified with polyethylene glycol (PEG) to retard the rate of blood clearance. Methods: PS-liposomes (size, 100 nm or 200 nm) were PEGylated with PEG2000 or PEG5000 at 1 or 5 mol%, and radiolabeled with 111In. For the study of uptake in vitro, liposomes were incubated with mouse peritoneal macrophages. Biodistribution studies in vivo were carried out in ddY mice. En face autoradiograms were obtained with apoE−/− mice upon intravenous injection of 111In-liposomes. Results: Uptake was decreased significantly at 5 mol% PEGylation in 100-nm PS-liposomes (*P < 0.05 vs. 0 mol%). All the PEGylated liposomes tested showed significantly lower uptake than the non-PEGylated control in 200-nm liposomes. In vivo results showed slower blood clearance in PEGylated liposomes. Autoradiograms in apoE−/− mice were well matched with Oil Red O staining. Additionally, 200-nm PS-liposomes modified with 5%PEG2000 ([111In]5%PEG2000PS200) showed the highest uptake to the region in vivo. Conclusions: As expected, PEGylation retarded the rate of blood clearance. In addition, it affected liposome uptake by macrophages in vitro. These results suggest that the balance between the rate of blood clearance and macrophage recognition is important, and [111In]5%PEG2000PS200 showed the best results in our investigation

  9. Neovascularization and coronary atherosclerotic plaque: cinematographic localization and quantitative histologic analysis.

    Science.gov (United States)

    Kamat, B R; Galli, S J; Barger, A C; Lainey, L L; Silverman, K J

    1987-10-01

    A new technique was developed for analyzing the neovascularization associated with coronary artery atherosclerosis: cinematography during silicone polymer injection of the coronary arteries of fixed and cleared human hearts, followed by histologic analysis in routine and 1-micron-thick, Epon-embedded sections. Twenty-two hearts obtained at autopsy were studied. On the basis of cinematographic findings, individual regions of the coronary arteries were classified as negative, positive, or abundantly positive for neovascularization. Positive and abundantly positive areas, which invariably occurred in segments exhibiting changes of atherosclerosis, contained numerous small vessels in the adventitia and outer media (4.7 +/- 1.5 and 9.8 +/- 1.3 [SE] vessel profiles/artery cross-section in positive and abundantly positive areas, versus 1.0 +/- 0.6 in negative regions). Abundantly positive areas, which occurred in coronary artery segments demonstrating the most extensive atherosclerotic change, contained numerous small vessels in the inner media or in the plaque itself. Some of these microvessels were in close proximity to mast cells, which represent potentially rich sources of mediators affecting vascular tone and permeability. Vessels were not observed in the inner media or in atherosclerotic plaque in areas designated either positive or negative by cinematography. These findings show how our approach can be used both to define the three-dimensional, in situ configuration of coronary artery neovascularization and to characterize the histology of this process in detail. They also confirm previous work indicating that areas of coronary arteries involved by atherosclerosis frequently exhibit extensive neovascularization. PMID:2443438

  10. Mitochondrial Mutations are Associated with Atherosclerotic Lesions in the Human Aorta

    Directory of Open Access Journals (Sweden)

    Igor A. Sobenin

    2012-01-01

    Full Text Available Somatic mutations of the human mitochondrial genome can be a possible determinant of atherosclerosis. To test this possibility, forty mitochondrial mutations were analyzed in the present study in order to see which of these mutations might be associated with atherosclerosis. Ten mitochondrial mutations belonging to mitochondrial genes MT-RNR1 (rRNA 12S; MT-TL1 (tRNA-Leu, recognizes UUR; MT-TL2 (tRNA-Leu, recognizes CUN; MT-ND1, MT-ND2, MT-ND5, and MT-ND6 (subunits 1, 2, 5, and 6, respectively, of NADH dehydrogenase; and MT-CYB (cytochrome b were potentially associated with atherosclerosis. From 29% (2 of 7 aortic samples upto 86% (6 of 7 aortic samples of aortic samples had a significant difference between atherosclerotic plaques and unaffected tissue, with the respect to the level of heteroplasmy for each mutation. Further, the homogenates of affected and normal intimae of 22 aortas were compared to reveal the average level of heteroplasmy for the above-mentioned 10 mutations. For five mutations, the mean level of heteroplasmy was significantly different in atherosclerotic intimal homogenates in comparison with the unaffected tissue. These mutations were A1555G, C3256T, T3336C, G13513A, and G15059A. Thus, it was demonstrated that at least five mitochondrial mutations occurring in MT-RNR1, MT-TL1, MT-ND2, MT-ND5, and MT-CYB genes are associated with atherosclerosis.

  11. Identification of atherosclerotic plaque components with intravascular ultrasound elastography in vivo: a Yucatan pig study.

    NARCIS (Netherlands)

    Korte, C.L. de; Sierevogel, M.J.; Mastik, F.; Strijder, C.; Schaar, J.A.; Velema, E.; Pasterkamp, G.; Serruys, P.W.; Steen, A.F.W. van der

    2002-01-01

    BACKGROUND: Intravascular ultrasound elastography assesses the local strain of the atherosclerotic vessel wall. In the present study, the potential to identify different plaque components in vivo was investigated. METHODS AND RESULTS: Atherosclerotic external iliac and femoral arteries (n=24) of 6 Y

  12. Microcalcifications in Early Intimal Lesions of Atherosclerotic Human Coronary Arteries

    Science.gov (United States)

    Roijers, Ruben B.; Debernardi, Nicola; Cleutjens, Jack P.M.; Schurgers, Leon J.; Mutsaers, Peter H.A.; van der Vusse, Ger J.

    2011-01-01

    Although calcium (Ca) precipitation may play a pathogenic role in atherosclerosis, information on temporal patterns of microcalcifications in human coronary arteries, their relation to expression of calcification-regulating proteins, and colocalization with iron (Fe) and zinc (Zn) is scarce. Human coronary arteries were analyzed post mortem with a proton microprobe for element concentrations and stained (immuno)histochemically for morphological and calcification-regulating proteins. Microcalcifications were occasionally observed in preatheroma type I atherosclerotic intimal lesions. Their abundance increased in type II, III, and IV lesions. Moreover, their appearance preceded increased expression of calcification-regulating proteins, such as osteocalcin and bone morphogenetic protein-2. In contrast, their presence coincided with increased expression of uncarboxylated matrix Gla protein (MGP), whereas the content of carboxylated MGP was increased in type III and IV lesions, indicating delayed posttranslational conversion of biologically inactive into active MGP. Ca/phosphorus ratios of the microcalcifications varied from 1.6 to 3.0, including amorphous Ca phosphates. Approximately 75% of microcalcifications colocalized with the accumulation of Fe and Zn. We conclude that Ca microprecipitation occurs in the early stages of atherosclerosis, inferring a pathogenic role in the sequel of events, resulting in overt atherosclerotic lesions. Microcalcifications may be caused by local events triggering the precipitation of Ca rather than by increased expression of calcification-regulating proteins. The high degree of colocalization with Fe and Zn suggests a mutual relationship between these trace elements and early deposition of Ca salts. PMID:21531376

  13. The Role of Microscopy in Understanding Atherosclerotic Lysosomal Lipid Metabolism

    Science.gov (United States)

    Gray Jerome, W.; Yancey, Patricia G.

    2003-02-01

    Microscopy has played a critical role in first identifying and then defining the role of lysosomes in formation of atherosclerotic foam cells. We review the evidence implicating lysosomal lipid accumulation as a factor in the pathogenesis of atherosclerosis with reference to the role of microscopy. In addition, we explore mechanisms by which lysosomal lipid engorgement occurs. Low density lipoproteins which have become modified are the major source of lipid for foam cell formation. These altered lipoproteins are taken into the cell via receptor-mediated endocytosis and delivered to lysosomes. Under normal conditions, lipids from these lipoproteins are metabolized and do not accumulate in lysosomes. In the atherosclerotic foam cell, this normal metabolism is inhibited so that cholesterol and cholesteryl esters accumulate in lysosomes. Studies of cultured cells incubated with modified lipoproteins suggests this abnormal metabolism occurs in two steps. Initially, hydrolysis of lipoprotein cholesteryl esters occurs normally, but the resultant free cholesterol cannot exit the lysosome. Further lysosomal cholesterol accumulation inhibits hydrolysis, producing a mixture of cholesterol and cholesteryl esters within swollen lysosomes. Various lipoprotein modifications can produce this lysosomal engorgement in vitro and it remains to be seen which modifications are most important in vivo.

  14. Clinical Study of Acoustic Densitometry Technique in Detecting Atherosclerotic Plaque

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To investigate the effect of Quyu Xiaoban Capsule (祛瘀消斑, QYXB) on the regressive treatment of atherosclerosis (AS) with acoustic densitometry (AD) technique. Methods: Eighty patients with AS were randomly divided into two groups, trial group was treated with QYXB and conventional medicine, and control group was treated with conventional medicine alone. Normal arterial wall and different types of atherosclerotic plaques were detected with AD technique before treatment and 10 months later. Resuits: The corrected averages in intimal echo intensity (AIIc%) were elevated in both groups but without significant difference, AIIc% of fatty plaques were increased in both groups and the value after treatment was significantly higher than that of pre-treatment in the trial group (68.12±5.54 vs 61.43±5.37, P<0.05).The increment rate of AIIc% in trial group was significantly higher than that in control group (10.9±5.1% vs2.5±5.5%, P<0.05). Conclusion: QYXB can stabilize the atherosclerotic plaque by increasing its acoustic density. Acoustic densitometry technique can differentiate the different histological plaques and monitor the histological changes of plaques during treatment.

  15. 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.

  16. 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.

  17. Spectral CT of carotid atherosclerotic plaque: comparison with histology

    International Nuclear Information System (INIS)

    To distinguish components of vulnerable atherosclerotic plaque by imaging their energy response using spectral CT and comparing images with histology. After spectroscopic calibration using phantoms of plaque surrogates, excised human carotid atherosclerotic plaques were imaged using MARS CT using a photon-processing detector with a silicon sensor layer and microfocus X-ray tube (50 kVp, 0.5 mA) at 38-μm voxel size. The plaques were imaged, sectioned and re-imaged using four threshold energies: 10, 16, 22 and 28 keV; then sequentially stained with modified Von Kossa, Perl's Prussian blue and Oil-Red O, and photographed. Relative Hounsfield units across the energies were entered into a linear algebraic material decomposition model to identify the unknown plaque components. Lipid, calcium, iron and water-like components of plaque have distinguishable energy responses to X-ray, visible on spectral CT images. CT images of the plaque surface correlated very well with histological photographs. Calcium deposits (>1,000 μm) in plaque are larger than iron deposits (<100 μm), but could not be distinguished from each other within the same voxel using the energy range available. Spectral CT displays energy information in image form at high spatial resolution, enhancing the intrinsic contrast of lipid, calcium and iron within atheroma. (orig.)

  18. Atherosclerotic Plaque Inflammation Varies Between Vascular Sites and Correlates With Response to Inhibition of Lipoprotein‐Associated Phospholipase A2

    Science.gov (United States)

    Fenning, Robert S.; Burgert, Mark E.; Hamamdzic, Damir; Peyster, Eliot G.; Mohler, Emile R.; Kangovi, Shreya; Jucker, Beat M.; Lenhard, Stephen C.; Macphee, Colin H.; Wilensky, Robert L.

    2015-01-01

    Background Despite systemic exposure to risk factors, the circulatory system develops varying patterns of atherosclerosis for unclear reasons. In a porcine model, we investigated the relationship between site‐specific lesion development and inflammatory pathways involved in the coronary arteries (CORs) and distal abdominal aortas (AAs). Methods and Results Diabetes mellitus (DM) and hypercholesterolemia (HC) were induced in 37 pigs with 3 healthy controls. Site‐specific plaque development was studied by comparing plaque severity, macrophage infiltration, and inflammatory gene expression between CORs and AAs of 17 DM/HC pigs. To assess the role of lipoprotein‐associated phospholipase A2 (Lp‐PLA2) in plaque development, 20 DM/HC pigs were treated with the Lp‐PLA2 inhibitor darapladib and compared with the 17 DM/HC untreated pigs. DM/HC caused site‐specific differences in plaque severity. In the AAs, normalized plaque area was 4.4‐fold higher (P<0.001) and there were more fibroatheromas (9 of the 17 animals had a fibroatheroma in the AA and not the COR, P=0.004), while normalized macrophage staining area was 1.5‐fold higher (P=0.011) compared with CORs. DM/HC caused differential expression of 8 of 87 atherosclerotic genes studied, including 3 important in inflammation with higher expression in the CORs. Darapladib‐induced attenuation of normalized plaque area was site‐specific, as CORs responded 2.9‐fold more than AAs (P=0.045). Conclusions While plaque severity was worse in the AAs, inflammatory genes and inflammatory pathways that use Lp‐PLA2 were more important in the CORs. Our results suggest fundamental differences in inflammation between vascular sites, an important finding for the development of novel anti‐inflammatory therapeutics. PMID:25672369

  19. Ghrelin receptor deficiency does not affect diet-induced atherosclerosis in low-density lipoprotein receptor-null mice

    Directory of Open Access Journals (Sweden)

    Kirk M. Habegger

    2011-11-01

    Full Text Available Objective: Ghrelin, a stomach-derived, secreted peptide, and its receptor (growth hormone secretagogue receptor, GHSR are known to modulate food intake and energy homeostasis. The ghrelin system is also expressed broadly in cardiovascular tissues. Since ghrelin has been associated with anti-inflammatory and anti-atherogenic properties, but is also well known to promote obesity and impair glucose metabolism, we investigated whether ghrelin has any impact on the development of atherosclerosis. The hypothesis that endogenous ghrelin signaling may be involved in atherosclerosis has not been tested previously Methods and Results: We crossed ghrelin receptor knockout mice (GHSr-/- into a low-density lipoprotein receptor-null (Ldlr-/- mouse line. In this model, atherosclerotic lesions were promoted by feeding a high-fat, high-cholesterol Western-type diet for 13 months, following a standard protocol. Body composition and glucose homeostasis were similar between Ldlr-/- and Ldlr/GHSR -/- ko mice throughout the study. Absence or presence of GHSr did not alter the apolipoprotein profile changes in response to diet exposure on an LDLRko background. Atherosclerotic plaque volume in the aortic arch and thoracic aorta were also not affected differentially in mice without ghrelin signaling due to GHSR gene disruption as compared to control LDLRko littermates. In light of the associations reported for ghrelin with cardiovascular disease in humans, the lack of a phenotype in these loss-of- function studies in mice suggests no directly functional role for endogenous ghrelin in either the inhibition or the promotion of diet-induced atherosclerosis.Conclusions: These data indicate that, surprisingly, the complex and multifaceted actions of endogenous ghrelin signaling on the cardiovascular system have minimal direct impact on atherosclerotic plaque progression as based on loss-of-function in a mouse model of the disease.

  20. Zooming in on the genesis of atherosclerotic plaque microcalcifications.

    Science.gov (United States)

    Ruiz, Jessica L; Weinbaum, Sheldon; Aikawa, Elena; Hutcheson, Joshua D

    2016-06-01

    Epidemiological evidence conclusively demonstrates that calcium burden is a significant predictor of cardiovascular morbidity and mortality; however, the underlying mechanisms remain largely unknown. These observations have challenged the previously held notion that calcification serves to stabilize the atherosclerotic plaque. Recent studies have shown that microcalcifications that form within the fibrous cap of the plaques lead to the accrual of plaque-destabilizing mechanical stress. Given the association between calcification morphology and cardiovascular outcomes, it is important to understand the mechanisms leading to calcific mineral deposition and growth from the earliest stages. We highlight the open questions in the field of cardiovascular calcification and include a review of the proposed mechanisms involved in extracellular vesicle-mediated mineral deposition. PMID:27040360

  1. Severe supraaortal atherosclerotic disease resembling Takayasu’s Arteritis

    Directory of Open Access Journals (Sweden)

    Bernhard Kis

    2007-07-01

    Full Text Available Bernhard Kis1,2, Thomas Liebig3,4, Peter Berlit11Department of Neurology, Alfried Krupp Hospital, Essen, Germany; 2Department of Psychiatry, University of Duisburg-Essen, Essen, Germany; 3Department of Neuroradiology, Alfried Krupp Hospital, Essen, Germany; 4Department of Neuroradiology, Technical University of Munich, Munich, GermanyAbstract: We report a case of a 64 year-old man whose clinical presentation and neuroimaging findings strikingly resembled those found in Takayasu’s Arteritis which is characterized by the triad of absent radial pulses, ischemic retinopathy, and carotid sinus hyperreflexia causing syncopes. Angiographically, the patient exhibited severe atherosclerotic changes of the supraaortic large vessels. Stent-assisted angioplasty resulted in both clinical improvement and increased cerebral blood flow as measured by angiography and ultrasound.Keywords: Takayasu’s arteritis, atherosclerosis, angiography, stent, angioplasty

  2. Lipid and protein maps defining arterial layers in atherosclerotic aorta

    Directory of Open Access Journals (Sweden)

    Marta Martin-Lorenzo

    2015-09-01

    Full Text Available Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to identify ongoing molecular changes in atherosclerosis development. Mass Spectrometry Imaging (MSI accounts with the unique advantage of analyzing proteins and metabolites (lipids while preserving their original localization; thus two dimensional maps can be obtained. Main molecular alterations were investigated in a rabbit model in response to early development of atherosclerosis. Aortic arterial layers (intima and media and calcified regions were investigated in detail by MALDI-MSI and proteins and lipids specifically defining those areas of interest were identified. These data further complement main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J. Proteomics. (In press; M. Martin-Lorenzo et al., J. Proteomics 108 (2014 465–468. [1,2].

  3. Tools for improving the diagnosis of atherosclerotic plaque using ultrasound

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

    topics have been investigated: an ultrasound pulse-echo simulation tool and a new compound imaging technique for improving visualization of atherosclerotic disease.A tool for simulation of the received electrical signal in a pulse-echo ultrasound system, due to a reflector surface of arbitrary geometry......, has been developed. The method is denoted the Diffraction Response Interpolation Method (DRIM) and is based on the pulse-echo diffraction impulse response method. The DRIM is a computationally efficient tool for calculating the integral of the spatially varying pulse-echo diffraction impulse response...... and experimentally. The MACI method operates by recording information about a given tissue region using a number of beam angles (typically 3 to 11) and combining the information into a single compound image (so-called spatial compounding). During the project a flexible experimental multi-channel ultrasound system...

  4. 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...... to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors...... of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5...

  5. Lipid and protein maps defining arterial layers in atherosclerotic aorta.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Balluff, Benjamin; Maroto, Aroa S; Carreira, Ricardo J; van Zeijl, Rene J M; Gonzalez-Calero, Laura; de la Cuesta, Fernando; Barderas, Maria G; Lopez-Almodovar, Luis F; Padial, Luis R; McDonnell, Liam A; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2015-09-01

    Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to identify ongoing molecular changes in atherosclerosis development. Mass Spectrometry Imaging (MSI) accounts with the unique advantage of analyzing proteins and metabolites (lipids) while preserving their original localization; thus two dimensional maps can be obtained. Main molecular alterations were investigated in a rabbit model in response to early development of atherosclerosis. Aortic arterial layers (intima and media) and calcified regions were investigated in detail by MALDI-MSI and proteins and lipids specifically defining those areas of interest were identified. These data further complement main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J. Proteomics. (In press); M. Martin-Lorenzo et al., J. Proteomics 108 (2014) 465-468.) [1,2]. PMID:26217810

  6. Microcalcifications in atherosclerotic lesion of apolipoprotein E-deficient mouse

    Science.gov (United States)

    Debernardi, Nicola; Roijers, Ruben B; Krams, Rob; de Crom, Rini; Mutsaers, Peter HA; van der Vusse, Ger J

    2010-01-01

    Evidence is accumulating that calcium-rich microdeposits in the vascular wall might play a crucial role in the onset and progression of atherosclerosis. Here we investigated an atherosclerotic lesion of the carotid artery in an established murine model, i.e. the apolipoprotein E-deficient (APOE−/−) mouse to identify (i) the presence of microcalcifications, if any, (ii) the elemental composition of microcalcifications with special reference to calcium/phosphorus mass ratio and (iii) co-localization of increased concentrations of iron and zinc with microcalcifications. Atherosclerosis was induced by a flow-divider placed around the carotid artery resulting in low and high shear-stress regions. Element composition was assessed with a proton microprobe. Microcalcifications, predominantly present in the thickened intima of the low shear-stress region, were surrounded by areas with normal calcium levels, indicating that calcium-precipitation is a local event. The diameter of intimal microcalcifications varied from 6 to 70 μm. Calcium/phosphorus ratios of microcalcifications varied from 0.3 to 4.8, mainly corresponding to the ratio of amorphous calcium-phosphate. Increased iron and zinc concentrations commonly co-localized with microcalcifications. Our findings indicate that the atherosclerotic process in the murine carotid artery is associated with locally accumulated calcium, iron and zinc. The calcium-rich deposits resemble amorphous calcium phosphate rather than pure hydroxyapatite. We propose that the APOE−/− mouse, in which atherosclerosis was evoked by a flow-divider, offers a useful model to investigate the pathophysiological significance of accumulation of elements such as calcium, iron and zinc. PMID:20804542

  7. 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...... levels of endotoxin were needed for TNF-α production equivalent to that of unprimed cells. The pro-inflammatory effect was selective as endotoxin-induced production of other pro-inflammatory cytokines was unaffected while production of anti-inflammatory interleukin-10 was diminished. These findings...... 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....

  8. Correlation of common carotid intima media thickness with atherosclerotic cardiovascular events in patients with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Vascular complications are a major cause of morbidity and mortality in patients with diabetes mellitus and affect the quality of life. Atherosclerosis, which is the major underlying risk factor, is accelerated in diabetes. To reduce morbidity and mortality, identification of patients with a high risk for development of vascular events is necessary. Apart from other risk prediction models, detection of subclinical atherosclerosis at common carotid site by B-mode ultrasonography which is a noninvasive and reliable method, can add to the benefit and improve risk prediction. Population based studies have revealed that increased Common Carotid Intima Media Thickness (CCIMT) is associated with prevalent coronary artery disease and is a surrogate marker of cardiovascular events. Aim was to evaluate whether increased CCIMT is associated with increased risk of cardiovascular events in patients with type 2 diabetes. A total of 90 patients with type 2 diabetes who were included in the study, were divided in two groups. Group 1: without vascular events and group 2: with vascular events. Apart from patient's demographics, detailed history of events physical examination, through blood analysis for fasting, post postprandial blood sugar, serum cholesterol, TG, renal function test glycosylated Hb, chest x-ray, ECG were recoded. CCIMT was measured by B-mode ultrasonography using high frequency linear transducer, by a specialist radiologist (blind to all clinical and laboratory findings) by standard protocol as described in literature. Mean of the three readings in each side were used for statistical analysis. Our results showed that of the 90 patients studied, 45 diabetes mellitus (DM) patients had atherosclerotic events and significantly higher CCIMT value (mean value of 1.005 +- 0.17 mm) whereas as 45 comparable DM patients without sclerotic events and lower CCIMT values (0.798 +- 0.12 mm) (p0.99 mm) had a statistically significant association with high odds ratios for

  9. Atherosclerotic Aneurysm of the Basilar Artery and Hydrocephalus. A Case Report

    Directory of Open Access Journals (Sweden)

    Ania Alvarado Borges

    2014-08-01

    Full Text Available Intracranial aneurysms are fairly common. Many of them produce no symptoms, often remaining undiagnosed during life. At autopsy, aneurysms of the basilar artery appear in 2 to 5% of the cases; among them, saccular and congenital aneurysms are more common than atherosclerotic and fusiform aneurysms. A case of atherosclerotic aneurysm of the basilar artery diagnosed at autopsy in an 88-year-old man is presented. This patient had been admitted with a diagnosis of ischemic stroke, intracranial hypertension and hydrocephalus, which led physicians to consider a posterior fossa tumor. This paper aims at presenting the autopsy findings that showed the presence of an atherosclerotic aneurysm of the basilar artery.

  10. Pregnancy outcome in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Bortoli, A; Pedersen, N; Duricova, D;

    2011-01-01

    Inflammatory bowel disease (IBD) frequently affects women during their reproductive years. Pregnancy outcome in women with IBD is well described, particularly in retrospective studies.......Inflammatory bowel disease (IBD) frequently affects women during their reproductive years. Pregnancy outcome in women with IBD is well described, particularly in retrospective studies....

  11. Hormonal control of inflammatory responses

    OpenAIRE

    Garcia-Leme, J.; Farsky, Sandra P

    1993-01-01

    Almost any stage of inflammatory and immunological responses is affected by hormone actions. This provides the basis for the suggestion that hormones act as modulators of the host reaction against trauma and infection. Specific hormone receptors are detected in the reactive structures in inflamed areas and binding of hormone molecules to such receptors results in the generation of signals that influence cell functions relevant for the development of inflammatory responses. Diversity of hormon...

  12. Somatostatin in inflammatory bowel disease

    OpenAIRE

    van Bergeijk, J D; Wilson, J H P

    1997-01-01

    Intestinal inflammation is controlled by various immunomodulating cells, interacting by molecular mediators. Neuropeptides, released by enteric nerve cells and neuroendocrine mucosa cells, are able to affect several aspects of the general and intestinal immune system, with both pro- as well as anti-inflammatory activities. In inflammatory bowel disease (IBD) there is both morphological as well as experimental evidence for involvement of neuropeptides in the pathogenesis. Somatostatin is the m...

  13. Hormonal control of inflammatory responses

    Directory of Open Access Journals (Sweden)

    J. Garcia-Leme

    1993-01-01

    Full Text Available Almost any stage of inflammatory and immunological responses is affected by hormone actions. This provides the basis for the suggestion that hormones act as modulators of the host reaction against trauma and infection. Specific hormone receptors are detected in the reactive structures in inflamed areas and binding of hormone molecules to such receptors results in the generation of signals that influence cell functions relevant for the development of inflammatory responses. Diversity of hormonal functions accounts for recognized pro- and anti-inflammatory effects exerted by these substances. Most hormone systems are capable of influencing inflammatory events. Insulin and glucocorticoids, however, exert direct regulatory effects at concentrations usually found in plasma. Insulin is endowed with facilitatory actions on vascular reactivity to inflammatory mediators and inflammatory cell functions. Increased concentrations of circulating glucocorticoids at the early stages of inflammation results in downregulation of inflammatory responses. Oestrogens markedly reduce the response to injury in a variety of experimental models. Glucagon and thyroid hormones exert indirect anti-inflammatory effects mediated by the activity of the adrenal cortex. Accordingly, inflammation is not only merely a local response, but a hormone-controlled process.

  14. 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

  15. Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

    2011-03-04

    Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

  16. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease.

    Directory of Open Access Journals (Sweden)

    Elena Nobili

    Full Text Available BACKGROUND: 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 its response to hypoxic stress. To this end, we examined Apoe(-/- mice fed a hypercholesterolemic diet and analysed the expression of key enzymes of the cys-LT pathway and their receptors (CysLT1/CysLT2 in normal and hypoxic myocardium as well as the potential contribution of cys-LT signaling to the acute myocardial response to hypoxia. METHODS AND PRINCIPAL FINDINGS: Myocardial biopsies from Apoe(-/- mice demonstrated signs of chronic inflammation with fibrosis, increased apoptosis and expression of IL-6, as compared to biopsies from C57BL/6J control mice. In addition, we found increased leukotriene C(4 synthase (LTC(4S and CysLT1 expression in the myocardium of Apoe(-/- mice. Acute bouts of hypoxia further induced LTC(4S expression, increased LTC(4S enzyme activity and CysLT1 expression, and were associated with increased extension of hypoxic areas within the myocardium. Inhibition of cys-LT signaling by treatment with montelukast, a selective CysLT1 receptor antagonist, during acute bouts of hypoxic stress reduced myocardial hypoxic areas in Apoe(-/- mice to levels equal to those observed under normoxic conditions. In human heart biopsies from 14 patients with chronic coronary artery disease mRNA expression levels of LTC(4S and CysLT1 were increased in chronic ischemic compared to non-ischemic myocardium, constituting a molecular basis for increased cys-LT signaling. CONCLUSION: Our results suggest that CysLT1 antagonists may have protective effects on the hypoxic heart, and improve the oxygen supply to areas of myocardial ischemia, for instance during episodes of sleep apnea.

  17. 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.

  18. A focus on inflammation as a major risk factor for atherosclerotic cardiovascular diseases.

    Science.gov (United States)

    Gregersen, Ida; Holm, Sverre; Dahl, Tuva B; Halvorsen, Bente; Aukrust, Pål

    2016-01-01

    Atherosclerosis is a dynamic, pathogenic process in the artery wall, with potential adverse outcome for the host. Acute events such as myocardial infarction and ischemic stroke often result from rupture of unstable atherosclerotic lesions. Understanding the underlying pathology of such lesions and why and when they rupture, is therefore of great interest for the development of new diagnostics and treatment. Inflammation is one of the key drivers of atherosclerotic plaque development and the interplay between inflammation and lipids constitutes the hallmark of atherosclerotic disease. This review summarizes the role of inflammation in atherosclerosis and presents some of the latest discoveries as well as unmet needs regarding the role of inflammation as major risk factor in atherosclerotic disease.

  19. Morphological study of atherosclerotic plaque and its application in vulnerability evaluation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The relationships between the morphological characteristics and the vulnerability of atherosclerotic plaque were analyzed theoretically and several suggestions were proposed to evaluate the plaque vulnerability. Validated by animal experiments and clinical studies, the theoretical results were confirmed.

  20. Inflammatory mechanisms of endometritis.

    Science.gov (United States)

    Woodward, E M; Troedsson, M H T

    2015-07-01

    Transient post breeding endometritis is a normal physiological reaction in the mare, as it is believed that an inflammatory response is necessary for the effective removal of contaminating bacteria and excess spermatozoa introduced into the uterus. While most mares can clear endometritis within a reasonable amount of time, persistent endometritis caused by either bacteria or spermatozoa can threaten the success of a pregnancy. A subpopulation of mares is susceptible to persistent endometritis, and these mares are a concern in equine reproductive medicine. Research has identified several factors that contribute to susceptibility; however, the exact mechanisms of the progression of the disease are still being elucidated. Current research focuses on endometrial gene expression during endometritis in an attempt to understand the timing of specific inflammatory processes involved with the development of susceptibility to persistent endometritis. With an increased understanding of the mechanisms involved with the disease, current treatments can be improved upon, and new treatments can be developed to target affected pathways. PMID:25537084

  1. 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;

    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....

  2. Effects of Mechanical Properties and Atherosclerotic Artery Size on Biomechanical Plaque Disruption - Mouse versus Human

    OpenAIRE

    Riou, Laurent M.; Broisat, Alexis; Ghezzi, Catherine; Finet, Gérard; Rioufol, Gilles; Gharib, Ahmed M.; Pettigrew, Roderic I.; Ohayon, Jacques

    2014-01-01

    Mouse models of atherosclerosis are extensively being used to study the mechanisms of atherosclerotic plaque development and the results are frequently extrapolated to humans. However, major differences have been described between murine and human atherosclerotic lesions and the determination of similarities and differences between these species has been largely addressed recently. This study takes over and extends previous studies performed by our group and related to the biomechanical chara...

  3. Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance.

    Science.gov (United States)

    Park, Arick C; Huang, Guorui; Jankowska-Gan, Ewa; Massoudi, Dawiyat; Kernien, John F; Vignali, Dario A; Sullivan, Jeremy A; Wilkes, David S; Burlingham, William J; Greenspan, Daniel S

    2016-02-12

    We have shown previously that collagen V (col(V)) autoimmunity is a consistent feature of atherosclerosis in human coronary artery disease and in the Apoe(-/-) mouse model. We have also shown sensitization of Apoe(-/-) mice with col(V) to markedly increase the atherosclerotic burden, providing evidence of a causative role for col(V) autoimmunity in atherosclerotic pathogenesis. Here we sought to determine whether induction of immune tolerance to col(V) might ameliorate atherosclerosis, providing further evidence for a causal role for col(V) autoimmunity in atherogenesis and providing insights into the potential for immunomodulatory therapeutic interventions. Mucosal inoculation successfully induced immune tolerance to col(V) with an accompanying reduction in plaque burden in Ldlr(-/-) mice on a high-cholesterol diet. The results therefore demonstrate that inoculation with col(V) can successfully ameliorate the atherosclerotic burden, suggesting novel approaches for therapeutic interventions. Surprisingly, tolerance and reduced atherosclerotic burden were both dependent on the recently described IL-35 and not on IL-10, the immunosuppressive cytokine usually studied in the context of induced tolerance and amelioration of atherosclerotic symptoms. In addition to the above, using recombinant protein fragments, we were able to localize two epitopes of the α1(V) chain involved in col(V) autoimmunity in atherosclerotic Ldlr(-/-) mice, suggesting future courses of experimentation for the characterization of such epitopes.

  4. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    Directory of Open Access Journals (Sweden)

    Funamoto M

    2016-08-01

    Full Text Available Masafumi Funamoto,1,2 Yoichi Sunagawa,1–3 Yasufumi Katanasaka,1–3 Yusuke Miyazaki,1,2 Atsushi Imaizumi,4 Hideaki Kakeya,5 Hajime Yamakage,2 Noriko Satoh-Asahara,2 Maki Komiyama,2 Hiromichi Wada,2 Koji Hasegawa,2 Tatsuya Morimoto1–3 1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 2Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, 3Shizuoka General Hospital, Shizuoka, 4Theravalues Corporation, Kioicho, Tokyo, 5Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan Purpose: COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD.Patients and methods: This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated.Results: There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure

  5. Quantitative profiling of oxylipins in plasma and atherosclerotic plaques of hypercholesterolemic rabbits.

    Science.gov (United States)

    Bojic, Lazar A; McLaren, David G; Harms, Amy C; Hankemeier, Thomas; Dane, Adrie; Wang, Sheng-Ping; Rosa, Ray; Previs, Stephen F; Johns, Douglas G; Castro-Perez, Jose M

    2016-01-01

    Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that affect a broad range of physiological processes, including cell proliferation, inflammation, inflammation resolution, and vascular function. Moreover, oxylipins are readily detectable in plasma, and certain subsets of oxylipins have been detected in human atherosclerotic lesions. Taken together, we set out to produce a detailed quantitative assessment of plasma and plaque oxylipins in a widely used model of atherosclerosis, to identify potential biomarkers of disease progression. We administered regular chow or regular chow supplemented with 0.5% cholesterol (HC) to male New Zealand white rabbits for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our targeted lipidomic analyses of oxylipins on plaques isolated from rabbits fed the HC diet detected 34 oxylipins, 28 of which were in compliance with our previously established quality control acceptance criteria. The arachidonic acid (AA) metabolite derived from the COX pathway, 6-keto-PGF1α was the most abundant plaque oxylipin, followed by the linoleic acid (LA) metabolites 9-HODE, 13-HODE and 9,12,13-TriHOME and the arachidonic acid (AA)-derivatives 11-HETE and 12-HETE. We additionally found that the most abundant oxylipins in plasma were three of the five most abundant oxylipins in plaque, namely 11-HETE, 13-HODE, and 9-HODE. The studies reported here make the first step towards a comprehensive characterization of oxylipins as potentially translatable biomarkers of atherosclerosis.

  6. Family history of atherosclerotic vascular disease is associated with the presence of abdominal aortic aneurysm.

    Science.gov (United States)

    Ye, Zi; Bailey, Kent R; Austin, Erin; Kullo, Iftikhar J

    2016-02-01

    We investigated whether family history (FHx) of atherosclerotic cardiovascular disease (ASCVD) was associated with presence of abdominal aortic aneurysm (AAA). The study cohort comprised of 696 patients with AAA (70±8 years, 84% men) and 2686 controls (68±10 years, 61% men) recruited from noninvasive vascular and stress electrocardiogram (ECG) laboratories at Mayo Clinic. AAA was defined as a transverse diameter of abdominal aorta ⩾ 3 cm or history of AAA repair. Controls were not known to have AAA. FHx was defined as having at least one first-degree relative with aortic aneurysm or with onset of ASCVD (coronary, cerebral or peripheral artery disease) before age 65 years. FHx of aortic aneurysm or ASCVD were each associated with presence of AAA after adjustment for age, sex, conventional risk factors and ASCVD: adjusted odds ratios (OR; 95% confidence interval): 2.17 (1.66-2.83, p aneurysm: adjusted OR: 1.27 (1.05-1.55, p = 0.01). FHx of ASCVD in multiple arterial locations was associated with higher odds of having AAA: the adjusted odds were 1.23 times higher for each additionally affected arterial location reported in the FHx (1.08-1.40, p = 0.01). Our results suggest both unique and shared environmental and genetic factors mediating susceptibility to AAA and ASCVD. PMID:26566659

  7. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models.

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE(-/-) and ApoE(-/-)Fbn1C1039G(+/-) mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  8. Colesevelam hydrochloride: reducing atherosclerotic coronary heart disease risk factors

    Directory of Open Access Journals (Sweden)

    Harold Bays

    2007-11-01

    Full Text Available Harold Bays1, Peter H Jones21L-MARC Research Center, Louisville KY, USA; 2Baylor College of Medicine, Houston, TX, USAAbstract: Colesevelam HCl is a bile acid sequestrant (BAS which has been specifically designed with a unique structure for the purpose of improving tolerability and reducing potential drug interactions compared to older BAS, such as cholestyramine and colestipol. As a class, BAS are known to reduce cholesterol and glucose levels, and to reduce atherosclerotic coronary heart disease (CHD risk as monotherapy, and in combination with other lipid-altering drug therapies. Colesevelam HCl has specifically been shown to reduce total and low-density lipoprotein (LDL cholesterol levels, and has been approved as a cholesterol-lowering drug since year 2000. It has also been shown to reduce glucose levels. This discussion reviews mechanisms by which BAS lower cholesterol, and potential mechanisms by which BAS lower glucose levels in patients with type 2 diabetes mellitus. Finally this paper specifically reviews colesevelam HCl’s pharmacology, lipid and glucose efficacy, safety/tolerability, and clinical use.Keywords: cholesterol, colesevelam HCl, coronary heart disease, diabetes mellitus, glucose, lipids

  9. Directional spatial frequency analysis of lipid distribution in atherosclerotic plaque

    Science.gov (United States)

    Korn, Clyde; Reese, Eric; Shi, Lingyan; Alfano, Robert; Russell, Stewart

    2016-04-01

    Atherosclerosis is characterized by the growth of fibrous plaques due to the retention of cholesterol and lipids within the artery wall, which can lead to vessel occlusion and cardiac events. One way to evaluate arterial disease is to quantify the amount of lipid present in these plaques, since a higher disease burden is characterized by a higher concentration of lipid. Although therapeutic stimulation of reverse cholesterol transport to reduce cholesterol deposits in plaque has not produced significant results, this may be due to current image analysis methods which use averaging techniques to calculate the total amount of lipid in the plaque without regard to spatial distribution, thereby discarding information that may have significance in marking response to therapy. Here we use Directional Fourier Spatial Frequency (DFSF) analysis to generate a characteristic spatial frequency spectrum for atherosclerotic plaques from C57 Black 6 mice both treated and untreated with a cholesterol scavenging nanoparticle. We then use the Cauchy product of these spectra to classify the images with a support vector machine (SVM). Our results indicate that treated plaque can be distinguished from untreated plaque using this method, where no difference is seen using the spatial averaging method. This work has the potential to increase the effectiveness of current in-vivo methods of plaque detection that also use averaging methods, such as laser speckle imaging and Raman spectroscopy.

  10. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  11. Imaging of atherosclerotic plaques by optical coherence tomography (OCT)

    Science.gov (United States)

    Perree, Jop; van Leeuwen, Ton G. J. M.; Pasterkamp, Gerard; Izatt, Joseph A.

    2000-05-01

    Optical Coherence Tomography (OCT) is an imaging technique that measures the intensity of light back scattered from sub- surface tissue structures with a very high resolution. This report describes the qualitative and quantitative correlation of OCT and histology measurements for plaque presence and thickness of caps overlying atherosclerotic plaques, respectively. Imaging of samples (n equals 12) was performed from the luminal side with 1300 nm 1 mW or 10 mW light sources, with coherence lengths of 21 and 16 micrometer, respectively. Samples were histologically processed and stained with H&E, EvG and picro-sirius red (PSR) and histological and OCT images were matched. For each sample, the presence of plaque was assessed and the minimal cap thickness was measured by means of histomorphometry and OCT. We found a sensitivity of 6/6 and a specificity of 5/6 for detection of plaques with OCT. Quantitative analysis showed a strong and significant correlation between OCT and histology cap thickness measurements (R2 equals 0.968). Thus, OCT is a sensitive method for detection of plaques, is quantitatively comparable to histology and holds promise as a high-resolution diagnostic tool for visualization of plaque cap thickness.

  12. Diagnosis of atherosclerotic tissue by resonance fluorescence spectroscopy

    Science.gov (United States)

    Neu, Walter; Haase, Karl K.; Tischler, Christian; Nyga, Ralf; Karsch, Karl R.

    1991-05-01

    Resonantly enhanced fluorescence emission induced by a tunable dye laser can be used for the identification of ablated atherosclerotic tissue. This method has been tested with anorganic samples exposed to air and to saline solution. A XeCl excimer laser pulse ((lambda) = 308 nm), delivered by a fused silica optical fiber, causes an efficient ablation of the irradiated samples. The wavelength of the narrow-band dye laser radiation is set to a strong transition of a specific species to be detected in the ablation plume. Taking into account the formation of the plume, the dye laser pulse is applied with a certain delay in order to excite resonantly the selected species in the plume. The resulting resonance fluorescence then is guided by optical fibers to an optical multi-channel analyzer system. Compared to the broad-band fluorescence during excimer laser ablation the resonance fluorescence signal shows a distinct and easily detectable sharp peak. The signal-to-background ratio is improved by one order of magnitude.

  13. Update on idiopathic inflammatory myopathies.

    Science.gov (United States)

    Briani, C; Doria, A; Sarzi-Puttini, P; Dalakas, M C

    2006-05-01

    The inflammatory myopathies are a group of acquired diseases, characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical, immuno-pathological and demographic features, three major diseases can be identified: dermatomyositis (DM); polymyositis (PM); and inclusion body myositis (IBM). New diagnostic criteria have recently been introduced, which are crucial for discriminating between the three different subsets of inflammatory myopathies and for excluding other disorders. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens, thus leading to fibre necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the main clinical, laboratory, electrophysiological, immunological and histologic features as well as the therapeutic options of the inflammatory myopathies.

  14. [Inflammatory myopathies. New concepts].

    Science.gov (United States)

    López Longo, Francisco Javier

    2008-03-01

    Myopathies are diseases characterized by the primary affection of skeletal muscle. In general they present with muscle weakness, pain, contracture, paresthesias, rigidity, or fatigue. They can be hereditary, such as muscle dystrophies, congenital, myotonic, metabolic, and myasthenic, or acquired. Among the latter ones we include idiopathic inflammatory myopathies (IIM), toxic, endocrine, or infectious myopathies and myasthenia gravis. There is a current acceptance of considerable clinical and histopathological overlap among some muscle dystrophies and some IIM. However, the molecular profile is different and characteristic in each myopathy and the study into the patterns of expression of genes in the muscle can be useful in their differential diagnosis, including that of IIM. PMID:21794553

  15. Novel visualization techniques towards identification of atherosclerotic patients at risk

    NARCIS (Netherlands)

    Jager, Nynke

    2014-01-01

    Atherosclerosis is an inflammatory disease of the artery wall. The genesis of atherosclerosis is associated with auto-immune diseases (the immune system turns against constituents of the own body) such as rheumatoid arthritis (RA). Atherosclerosis is a chronic process that leads to the formation of

  16. Improvement of renal function after opening occluded atherosclerotic renal arteries.

    Science.gov (United States)

    Kanamori, Hiroshi; Toma, Masanao; Fukatsu, Atsushi

    2009-09-01

    Percutaneous transluminal renal angioplasty (PTRA) with stenting has been effective in the control of hypertension, renal function and pulmonary edema caused by atherosclerotic renal artery stenosis (ARAS). However, concerning the viability of renal function, this procedure has not been fully established, especially in the presence of renal atrophy or severe renal parenchymal disease. We report a dramatically improved case of acute renal failure caused by acute worsening ARAS treated by stenting. A 72-year-old female was admitted for accelerated renal dysfunction (serum ceatinine; 1.2-2.3 mg/dl) and hypertension (190/100 mmHg). At 10 days after admission, the patient's serum ceatinine increased to 6.7 mg/dl, her pulmonary edema was exaggerated and hemodialysis was required. Ultrasonography showed bilateral high-echoic kidneys, but no apparent finding of renal artery stenosis (RAS). At day 15, computed tomographic angiography indicated bilateral ostial RAS. Renal angiography demonstrated total occlusion of the right and severe (90%) disease in the left. ARAS was diagnosed by intravascular ultrasonography. The guidewire was inserted in both renal arteries, PTRA with stenting was performed in the right and a stent was directly implanted in the left. Immediately, each kidney enlarged to almost normal size, leading to satisfactory urination. She was released from hemodialysis the next day since her serum creatinine was normal and the pulmonary edema was improved. Although there is still no reliable prognostic factor including resistive index or kidney size, it is important that PTRA with stenting in ARAS should be considered in a case of accelerated renal dysfunction because of the possible improvement. PMID:19726830

  17. Optical detection of structural changes in human carotid atherosclerotic plaque

    Science.gov (United States)

    Korol, R. M.; Canham, P. B.; Finlay, H. M.; Hammond, R. R.; Quantz, M.; Ferguson, G. G.; Liu, L. Y.; Lucas, A. R.

    2005-08-01

    Background: Arterial bifurcations are commonly the sites of developing atherosclerotic plaque that lead to arterial occlusions and plaque rupture (myocardial infarctions and strokes). Laser induced fluorescence (LIF) spectroscopy provides an effective nondestructive method supplying spectral information on extracellular matrix (ECM) protein composition, specifically collagen and elastin. Purpose: To investigate regional differences in the ECM proteins -- collagen I, III and elastin in unstable plaque by analyzing data from laser-induced fluorescence spectroscopy of human carotid endarterectomy specimens. Methods: Gels of ECM protein extracts (elastin, collagen types I & III) were measured as reference spectra and internal thoracic artery segments (extra tissue from bypass surgery) were used as tissue controls. Arterial segments and the endarterectomy specimens (n=21) were cut into 5mm cross-sectional rings. Ten fluorescence spectra per sampling area were then recorded at 5 sites per ring with argon laser excitation (357nm) with a penetration depth of 200 μm. Spectra were normalized to maximum intensity and analyzed using multiple regression analysis. Tissue rings were fixed in formalin (within 3 hours of surgery), sectioned and stained with H&E or Movat's Pentachrome for histological analysis. Spectroscopy data were correlated with immunohistology (staining for elastin, collagen types I, III and IV). Results: Quantitative fluorescence for the thoracic arteries revealed a dominant elastin component on the luminal side -- confirmed with immunohistology and known artery structure. Carotid endarterectomy specimens by comparison had a significant decrease in elastin signature and increased collagen type I and III. Arterial spectra were markedly different between the thoracic and carotid specimens. There was also a significant elevation (pdetected in the carotid specimens.

  18. 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

  19. Comorbidity in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Antonio López San Román; Fernando Mu(n)oz

    2011-01-01

    Patients with inflammatory bowel disease (IBD) can be affected by other unrelated diseases. These are called comorbid conditions, and can include any secondary health problem that affects a person suffering from a primary or main disease, and which is neither linked physiopathologically to the primary condition, nor is it due to the treatments used for the primary condition or to its long-term anatomical or physiological consequences.Different comorbid conditions, as well as their influence on IBD, are discussed.

  20. Increased expression of phosphorylated forms of heat-shock protein-27 and p38MAPK in macrophage-rich regions of fibro-fatty atherosclerotic lesions in the rabbit.

    Science.gov (United States)

    Shafi, Shahida; Codrington, Rosalind; Gidden, Lewis Michael; Ferns, Gordon Ashley Anthony

    2016-02-01

    We aimed to assess the expression and distribution of Hsp27, pHsp27 (Ser82), p38MAPK and p-p38MAPK in fibro-fatty atherosclerotic lesions and the myocardium of hypercholesterolaemic rabbits. Male New Zealand white rabbits were fed a high-cholesterol diet for 18 weeks, maintaining serum cholesterol at approximately 20 mmol/l over this period. Aortic arch and myocardial tissues were analysed by Western blot, immunohistochemistry and double immunofluorescence. Plasma Hsp27 levels were measured by ELISA. There was a significant increase in the expression of monomeric and dimeric forms of Hsp27, together with pHsp27 (Ser82), p38MAPK and p-p38MAPK in the fibro-fatty atherosclerotic lesions (P < 0.01; P < 0.05; P < 0.001; and P < 0.001, respectively) and the myocardial tissues (P < 0.001) from the cholesterol-fed rabbits compared with equivalent tissues from controls when the plasma concentration was low. Immunohistochemical analysis of the fibro-fatty lesions showed marked increases in Hsp27 and pHsp27 (Ser82) immunoreactivity. Double immunostaining showed intense expression of pHsp27 and p-p38MAPK in regions that were rich in macrophages, suggesting a close association with these inflammatory cells, whereas, in regions rich in smooth muscle cells, only p-p38MAPK was found to be strongly expressed. An increased expression of pHsp27 (Ser82) was spatially associated with increased p-p38MAPK within fibro-fatty atherosclerotic lesions and was colocalized to regions rich in macrophages. The initial increase in plasma Hsp27 levels may reflect the increase in systemic inflammation and oxidative stress in the early phases of disease. The falling concentrations subsequently may be coincident with the development of the advanced atherosclerotic lesions.

  1. Tissue Factor and Systemic Lupus Erythematosus Compncated by Atherosclerotic Lesions

    Institute of Scientific and Technical Information of China (English)

    洪梅

    2011-01-01

    @@ We should grasp the entirety when studying the pathogenesis and treatment of disease.The pathogenesis of SLE pafients with atherosclerosis (AS)involves lipid infiltration,inflammatory reaction,immune injury,platelet aggregafion,thrombosis,etc,and the drug therapy includes lipid-lowering,anti-inflammatory,immunosuppression,anti-platelet,and anticoagulation based on corresponding theories.But these drugs,the effect of which is not ideal,principally aim at just part of pathological process.In fact,the AS lesioas in SLE in different pathological processes are closely linked,and therefore,it is very important to study the internal relations of different pathological processes and lookfor new therapeutic targets for blocking difierent pathological processes simultaneously,so as to improve the therapeutic efficacy.

  2. Placental growth factor promotes atherosclerotic intimal thickening and macrophage accumulation

    OpenAIRE

    Khurana, R.; Moons, L; Shafi, S.; A. Luttun; Collen, D; Martin, J. F.; Carmeliet, P.; Zachary, I. C.

    2005-01-01

    Background: Placental growth factor (PlGF) has been implicated in the pathophysiological angiogenesis and monocyte recruitment that underlie chronic inflammatory disease, but its role in atherosclerosis has not been examined. We investigated the effects of exogenous PlGF, delivered by adenoviral gene transfer, on atherogenic intimal thickening and macrophage accumulation induced by collar placement around the rabbit carotid artery and examined the effects of PlGF deficiency on atherosclerosis...

  3. 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.

  4. MR histology of advanced atherosclerotic lesions of ApoE- knockout mice

    Science.gov (United States)

    Naumova, A.; Yarnykh, V.; Ferguson, M.; Rosenfeld, M.; Yuan, C.

    2016-02-01

    The purposes of this study were to examine the feasibility of determining the composition of advanced atherosclerotic plaques in fixed ApoE-knockout mice and to develop a time-efficient microimaging protocol for MR histological imaging on mice. Five formalin-fixed transgenic ApoE-knockout mice were imaged at the 9.4T Bruker BioSpec MR scanner using 3D spoiled gradient-echo sequence with an isotropic field of view of 24 mm3; TR 20.8 ms; TE 2.6 ms; flip angle 20°, resulted voxel size 47 × 63 × 94 pm3. MRI examination has shown that advanced atherosclerotic lesions of aorta, innominate and carotid arteries in ApoE-knockout mice are characterized by high calcification and presence of the large fibrofatty nodules. MRI quantification of atherosclerotic lesion components corresponded to histological assessment of plaque composition with a correlation coefficient of 0.98.

  5. Serum cyclin-dependent kinase 9 is a potential biomarker of atherosclerotic inflammation

    Science.gov (United States)

    Han, Yeming; Zhao, Shanshan; Gong, Yaoqin; Hou, Guihua

    2016-01-01

    Atherosclerotic coronary artery disease (CAD) is one of the most prevalent diseases worldwide. Atherosclerosis was considered to be the single most important contributor to CAD. In this study, a distinct serum protein expression pattern in CAD patients was demonstrated by proteomic analysis with two-dimensional gel electrophoresis coupled with mass spectrometry. In particular, CDK9 was found to be highly elevated in serum, monocytes and artery plaque samples of CAD patients. Furthermore, there was high infiltration of CD14+ monocytes/macrophages within artery plaques correlated with the expression of CDK9. Moreover, Flavopiridol (CDK9 inhibitor) could inhibit THP-1 cell (monocytic acute leukemia cell line) proliferation by targeting CDK9. Altogether, These findings indicate that CDK9 represent an important role for inflammation in the pathogenesis of atherosclerosis. It may be a potential biomarker of atherosclerotic inflammation and offer insights into the pathophysiology and targeted therapy for atherosclerotic CAD. PMID:26636538

  6. Magnetic Resonance Imaging of Atherosclerotic Lesion with New Devised Animal Surface Coil

    Institute of Scientific and Technical Information of China (English)

    ZHAO Bing-hui; LI Ming-hua; ZHAO Qing; CHENG Ying-sheng; XIAO Yun-feng; ZHAO Jia-min

    2008-01-01

    The ability of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) with a new devised animal surface coil was analyzed in identifying atherosclerotic plaques in the rabbit medium-sized iliac artery (IA).Then a comparative analysis of multi-detector computed tomography (MDCT) and DCE MRI was clone in discerning morphology and components of 80 atherosclerotic plaques identified by histopathology.It shows that the DCE MRI may be an emerging noninvasive and economic way to characterize atherosclerotic plaques at present.What's more,a new devised animal surface coil would further improve the signal-to-noise ratio (SNR) and the quality of imaging.However,CT angiography (CTA) may be better than MR angiography(MRA) in detecting vessel stenosis.

  7. Protective effects ofMallotus furetianus on functions of endothelial progenitor cells in atherosclerotic rats

    Institute of Scientific and Technical Information of China (English)

    Yue-Li Liu; Dan Zhou; Lian-Bo Lin; Chen Yang

    2015-01-01

    Objective:To investigate protective effects ofMallotus furetianus(M. furetianus)on functions of endothelial progenitor cells (EPCs) in atherosclerotic rats.Methods:Atherosclerosis was established by intraperitoneal injection of vitamin D3 combined with high fat diet for 9 weeks. Extracts ofM. furetianus were given to prevent damage of EPCs in dose of 0.081 g/kg and 0.026 g/kg. Rats were sacrificed, and then mononuclear cells were isolated from bone marrow to culture EPCs and test the functions of EPCs.Results:M. furetianus can improve the capacities of EPCs on proliferation, migration, adhesion, and tubule formation in doses of 0.081 g/kg; improve adhesion, and tubule formation in dose of 0.026 g/kg in atherosclerotic rats. Conclusion:M. furetianus can protect functions of EPCs in atherosclerotic rats.

  8. Orp8 deficiency in bone marrow-derived cells reduces atherosclerotic lesion progression in LDL receptor knockout mice.

    Directory of Open Access Journals (Sweden)

    Erik van Kampen

    Full Text Available INTRODUCTION: Oxysterol binding protein Related Proteins (ORPs mediate intracellular lipid transport and homeostatic regulation. ORP8 downregulates ABCA1 expression in macrophages and cellular cholesterol efflux to apolipoprotein A-I. In line, ORP8 knockout mice display increased amounts of HDL cholesterol in blood. However, the role of macrophage ORP8 in atherosclerotic lesion development is unknown. METHODS AND RESULTS: LDL receptor knockout (KO mice were transplanted with bone marrow (BM from ORP8 KO mice and C57Bl/6 wild type mice. Subsequently, the animals were challenged with a high fat/high cholesterol Western-type diet to induce atherosclerosis. After 9 weeks of Western-Type diet feeding, serum levels of VLDL cholesterol were increased by 50% in ORP8 KO BM recipients compared to the wild-type recipients. However, no differences were observed in HDL cholesterol. Despite the increase in VLDL cholesterol, lesions in mice transplanted with ORP8 KO bone marrow were 20% smaller compared to WT transplanted controls. In addition, ORP8 KO transplanted mice displayed a modest increase in the percentage of macrophages in the lesion as compared to the wild-type transplanted group. ORP8 deficient macrophages displayed decreased production of pro-inflammatory factors IL-6 and TNFα, decreased expression of differentiation markers and showed a reduced capacity to form foam cells in the peritoneal cavity. CONCLUSIONS: Deletion of ORP8 in bone marrow-derived cells, including macrophages, reduces lesion progression after 9 weeks of WTD challenge, despite increased amounts of circulating pro-atherogenic VLDL. Reduced macrophage foam cell formation and lower macrophage inflammatory potential are plausible mechanisms contributing to the observed reduction in atherosclerosis.

  9. 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.

  10. 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.

  11. 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

    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...

  12. 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

    2009-01-01

    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 a

  13. 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.

  14. Development of a near infrared fluorescence catheter: operating characteristics and feasibility for atherosclerotic plaque detection

    International Nuclear Information System (INIS)

    We present a one-dimensional optical fibre-based imaging catheter specifically developed for the atherosclerotic plaque detection of emerging novel near infrared fluorescence imaging agents. We show that femtomole amounts of fluorochromes can be detected, especially in the presence of a blood-free medium. We further studied the catheter responses for a wide range of laser powers and biologically relevant concentrations of fluorochrome. In vitro tissue-like phantoms and human carotid plaque specimen measurements further demonstrate the feasibility of atherosclerotic plaque detection

  15. Molecular imaging of atherosclerotic lesions by positron emission tomography - can it meet the expectations?

    Science.gov (United States)

    Brammen, Lindsay; Steiner, Sabine; Berent, Robert; Sinzinger, Helmut

    2016-01-01

    Early non-invasive imaging of atherosclerosis and in particular the detection of lesions at risk with high specificity could significantly affect cardiovascular morbidity and mortality. Conventional nuclear medicine approaches, in particular using autologous radiolabeled lipoproteins, can be related to histopathological findings; however, they fail to identify lesions at risk. Positron emission tomography (PET) tracers with much better physical properties have been examined, the most detailed information being available for F-18-deoxyglucose (FDG) and F-18-sodium fluoride (NaF). These two approaches are sensitive to different biochemical mechanisms, i.e. inflammation and microcalcification. Initial enthusiasm, in particular for F-18-FDG, has disappeared, although for F-18-NaF there is some hope, but this is not a breakthrough. No tracer is available so far that is able to identify a specific characteristic of a lesion prone to rupture. Other PET tracers in the pipeline have been examined, mainly in experimental models and only a few in patients, but they failed to contribute significantly to early lesion discovery and do not support great expectations. The key question is: Do we understand what we see? Moreover, methodological problems, a lack of standardization of imaging protocols and aspects of quantification provide a wide range for potential future improvements. While monitoring a therapeutic intervention seems to be possible for both F-18-FDG and F-18-NaF, highly specific early identification of lesions at risk by PET imaging is still far away. As of today, PET is not ready for routine clinical judgment of atherosclerotic lesions at risk to rupture. Even if all these problems can be solved, radiation exposure will still remain a concern, in particular for repeated studies.

  16. Vitamin K-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype.

    Directory of Open Access Journals (Sweden)

    Leon J Schurgers

    Full Text Available BACKGROUND: Vitamin K-antagonists (VKA are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE(-/- model of atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: A total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD. VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE(-/- mice (10 weeks received a Western type diet (WTD for 12 weeks, after which mice were fed a WTD supplemented with vitamin K(1 (VK(1, 1.5 mg/g or vitamin K(1 and warfarin (VK(1&W; 1.5 mg/g & 3.0 mg/g for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden. CONCLUSIONS/SIGNIFICANCE: VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE(-/- mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle.

  17. HIV-infection, atherosclerosis and the inflammatory pathway: candidate gene study in a Spanish HIV-infected population.

    Directory of Open Access Journals (Sweden)

    Laura Ibáñez

    Full Text Available BACKGROUND: Higher prevalence of atherosclerosis and higher cardiovascular risk is observed in HIV-infected individuals. The biological mechanisms underlying these processes are unclear. Several studies have implicated genetic variants in the inflammatory genes in cardiovascular disease and in HIV natural course infection. METHODS & FINDINGS: In this study we have tested the possible association between genetic variants in several inflammatory genes and asymptomatic cardiovascular disease measured by carotid intima media thickness (cIMT and atherosclerotic plaque presence as dependent variables in 213 HIV-infected individuals. A total of 101 genetic variants in 25 candidate genes have been genotyped. Results were analyzed using Plink and SPSS statistical packages. We have found several polymorphisms in the genes ALOX5 (rs2115819 p = 0.009, ALOX5AP (rs9578196 p = 0.007; rs4769873 p = 0.004 and rs9315051 p = 0.0004, CX3CL1 (rs4151117 p = 0.040 and rs614230 p = 0.015 and CCL5 (rs3817655 p = 0.018 and rs2107538 p = 0.018 associated with atherosclerotic plaque. cIMT mean has been associated with CRP (1130864 p = 0.0003 and rs1800947 p = 0.008, IL1RN (rs380092 p = 0.002 and ALOX5AP (rs3885907 p = 0.02 genetic variants. CONCLUSIONS: In this study we have found modest associations between genetic variants in several inflammatory genes and atherosclerotic plaque or cIMT. Nevertheless, our study adds evidence to the association between inflammatory pathway genetic variants and the atherosclerotic disease in HIV-infected individuals.

  18. Numerical observer for atherosclerotic plaque classification in spectral computed tomography.

    Science.gov (United States)

    Lorsakul, Auranuch; Fakhri, Georges El; Worstell, William; Ouyang, Jinsong; Rakvongthai, Yothin; Laine, Andrew F; Li, Quanzheng

    2016-07-01

    Spectral computed tomography (SCT) generates better image quality than conventional computed tomography (CT). It has overcome several limitations for imaging atherosclerotic plaque. However, the literature evaluating the performance of SCT based on objective image assessment is very limited for the task of discriminating plaques. We developed a numerical-observer method and used it to assess performance on discrimination vulnerable-plaque features and compared the performance among multienergy CT (MECT), dual-energy CT (DECT), and conventional CT methods. Our numerical observer was designed to incorporate all spectral information and comprised two-processing stages. First, each energy-window domain was preprocessed by a set of localized channelized Hotelling observers (CHO). In this step, the spectral image in each energy bin was decorrelated using localized prewhitening and matched filtering with a set of Laguerre-Gaussian channel functions. Second, the series of the intermediate scores computed from all the CHOs were integrated by a Hotelling observer with an additional prewhitening and matched filter. The overall signal-to-noise ratio (SNR) and the area under the receiver operating characteristic curve (AUC) were obtained, yielding an overall discrimination performance metric. The performance of our new observer was evaluated for the particular binary classification task of differentiating between alternative plaque characterizations in carotid arteries. A clinically realistic model of signal variability was also included in our simulation of the discrimination tasks. The inclusion of signal variation is a key to applying the proposed observer method to spectral CT data. Hence, the task-based approaches based on the signal-known-exactly/background-known-exactly (SKE/BKE) framework and the clinical-relevant signal-known-statistically/background-known-exactly (SKS/BKE) framework were applied for analytical computation of figures of merit (FOM). Simulated data of a

  19. Numerical observer for atherosclerotic plaque classification in spectral computed tomography.

    Science.gov (United States)

    Lorsakul, Auranuch; Fakhri, Georges El; Worstell, William; Ouyang, Jinsong; Rakvongthai, Yothin; Laine, Andrew F; Li, Quanzheng

    2016-07-01

    Spectral computed tomography (SCT) generates better image quality than conventional computed tomography (CT). It has overcome several limitations for imaging atherosclerotic plaque. However, the literature evaluating the performance of SCT based on objective image assessment is very limited for the task of discriminating plaques. We developed a numerical-observer method and used it to assess performance on discrimination vulnerable-plaque features and compared the performance among multienergy CT (MECT), dual-energy CT (DECT), and conventional CT methods. Our numerical observer was designed to incorporate all spectral information and comprised two-processing stages. First, each energy-window domain was preprocessed by a set of localized channelized Hotelling observers (CHO). In this step, the spectral image in each energy bin was decorrelated using localized prewhitening and matched filtering with a set of Laguerre-Gaussian channel functions. Second, the series of the intermediate scores computed from all the CHOs were integrated by a Hotelling observer with an additional prewhitening and matched filter. The overall signal-to-noise ratio (SNR) and the area under the receiver operating characteristic curve (AUC) were obtained, yielding an overall discrimination performance metric. The performance of our new observer was evaluated for the particular binary classification task of differentiating between alternative plaque characterizations in carotid arteries. A clinically realistic model of signal variability was also included in our simulation of the discrimination tasks. The inclusion of signal variation is a key to applying the proposed observer method to spectral CT data. Hence, the task-based approaches based on the signal-known-exactly/background-known-exactly (SKE/BKE) framework and the clinical-relevant signal-known-statistically/background-known-exactly (SKS/BKE) framework were applied for analytical computation of figures of merit (FOM). Simulated data of a

  20. {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.)

  1. 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...

  2. Differential analysis of clinical features in atherosclerotic renal artery stenosis and benign nephrosclerosis

    Institute of Scientific and Technical Information of China (English)

    郭云珊

    2006-01-01

    Objective To analyze and compare the clinical characteristics of atherosclerotic renal artery stenosis (ARAS) and benign nephrosclerosis (BN) in order to distinguish the ARAS from BN. Methods A retrospective study was performed on 82 hypertensive patients with renal injury. Patients were divided into BN and ARAS group according to renal artery doppler scanning. The

  3. 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

    2005-01-01

    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 Vasc

  4. Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice

    NARCIS (Netherlands)

    Leppänen, P.; Luoma, J.S.; Hofker, M.H.; Havekes, L.M.; Ylä-Herttuala, S.

    1998-01-01

    Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam

  5. 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.

  6. 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...

  7. Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques

    NARCIS (Netherlands)

    Queiroz, Karla C. S.; Bijlsma, Maarten F.; Tio, Rene A.; Zeebregts, Clark J.; Dunaeva, Marina; Ferreira, Carmen V.; Fuhler, Gwenny M.; Kuipers, Ernst J.; Alves, Maria M.; Rezaee, Farhad; Spek, C. Arnold; Peppelenbosch, Maikel P.

    2012-01-01

    The major cause for plaque instability in atherosclerotic disease is neoangiogenic revascularization, but the factors controlling this process remain only partly understood. Hedgehog (HH) is a morphogen with important functions in revascularization, but its function in human healthy vessel biology a

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Ex vivo coronary atherosclerotic plaque characterization with multi-detector-row CT

    International Nuclear Information System (INIS)

    Multi-detector-row CT angiography (CTA) is a new technology that allows for non-invasive investigation of coronary atherosclerosis in patients. The relation between the morphology of atherosclerotic plaques assessed by CTA and histopathology is unknown. We investigated 11 human cadaver heart specimens. A mixture of methylcellulose and CT contrast media was injected into the coronary arteries to achieve in-vivo-like contrast enhancement within the coronary artery lumen. The morphologic pattern of atherosclerotic lesions found on CTA images and the tissue attenuation of non-calcified plaques were determined. After CTA imaging, atherosclerotic lesions in the coronary arteries were macroscopically identified and characterized histopathologically according to American Heart Association criteria. A total of 50 and 40 lesions were found macroscopically and by CTA, respectively. Thirty-three lesions could have been compared directly. The sensitivity of CTA compared with macroscopic detection of atheromas, fibroatheromas, fibrocalcified, and calcified lesions was 73, 70, 86, and 100%, respectively. The mean CT attenuation of predominantly lipid-rich and fibrous-rich plaques was significantly different (47±9 and 104±28 HU, respectively; p<0.01). Atherosclerotic coronary plaques detected by CTA may represent different stages of coronary atherosclerosis. The tissue attenuation of non-calcified plaques may allow for assessment of their predominant component. (orig.)

  10. Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration

    NARCIS (Netherlands)

    Valk, van der Fleur M.; Wijk, van Diederik F.; Lobatto, Mark E.; Verberne, Hein J.; Storm, Gert; 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.; Mulder, Willem J.M.; Stroes, Erik S.G.

    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

  11. Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner

    NARCIS (Netherlands)

    Westein, Erik; Meer, van der Andries D.; Kuijpers, Marijke J.E.; Frimat, Jean-Philippe; Berg, van den Albert; Heemskerk, Johan W.M.

    2013-01-01

    Rupture of a vulnerable atherosclerotic plaque causes thrombus formation and precipitates cardiovascular diseases. In addition to the thrombogenic content of a plaque, also the hemodynamic microenvironment plays a major role in thrombus formation. How the altered hemodynamics around a plaque promote

  12. Detection of Fungal Elements in Atherosclerotic Plaques Using Mycological, Pathological and Molecular Methods

    Directory of Open Access Journals (Sweden)

    Omid MASOUMI

    2015-10-01

    Full Text Available Background: The aim of this study was to detect fungi in atherosclerotic plaques and investigate their possible role in atherosclerosis.Methods: Coronary atherosclerotic plaques specimen were obtained from patients with atherosclerosis. Direct exami-nation, culture, histopathology study, PCR and sequencing were performed to detect/identify the mycotic elements in the plaques. Age, sex, smoking, obesity, hypertension, hyperlipidemia, family history of heart diseases and diabetes were considered and data were analyzed using Chi Square test by SPSS version 15.Results: A total of 41 specimens were analyzed. Direct examination for fungal elements was negative in all cases but in culture only one specimen grew as a mold colony. The presence of fungal elements were confirmed in 6 and 2 tissue sections stained by Gomori methenamine silver and Hematoxylin and Eosin methods, respectively. Using PCR, 11 cases were positive for fungi. The DNA sequence analysis of six positive specimens which were randomly selected revealed fungi as Candida albicans (n=3, Candida guilliermondii (n=2 and Monilia sp. (n=1.Conclusion: A significant association between the presence of fungi in atherosclerotic plaques and severity of athero-genesis and atherosclerotic disease was not found. This could be due to limited numbers of patients included in our study. However, the presence of fungal elements in 26.8% of our specimens is considerable and the results does not exclude the correlation between the presence of fungi with atherosclerosis and coronary artery disease.

  13. Macrophage p53 controls macrophage death in atherosclerotic lesions of apolipoprotein E deficient mice

    NARCIS (Netherlands)

    Boesten, L.S.M.; Zadelaar, A.S.M.; Nieuwkoop, A. van; Hu, L.; Teunisse, A.F.A.S.; Jochemsen, A.G.; Evers, B.; Water, B. van de; Gijbels, M.J.J.; Vlijmen, B.J.M. van; Havekes, L.M.; Winther, M.P.J. de

    2009-01-01

    The cellular composition of atherosclerotic lesions is determined by many factors including cell infiltration, proliferation and cell death. Tumor suppressor gene p53 has been shown to regulate both cell proliferation and cell death in many cell types. In the present study, we investigated the role

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

    Science.gov (United States)

    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...

  15. Atherosclerotic plaque fibrous cap assessment under an oblique scan plane orientation in carotid MRI

    NARCIS (Netherlands)

    Nieuwstadt, H.A.; Van der Lugt, A.; Kassar, Z.A.M.; Breeuwer, M.; Van der Steen, A.F.W.; Gijsen, F.J.H.

    2014-01-01

    Carotid magnetic resonance imaging (MRI) is used to noninvasively assess atherosclerotic plaque fibrous cap (FC) status, which is closely related to ischemic stroke. Acquiring anisotropic voxels improves in-plane visualization, however, an oblique scan plane orientation could then obscure a FC (i.e.

  16. Influence of insonification angle on echogenicity of B-mode images of atherosclerotic plaque in vitro

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Jespersen, Søren Kragh; Hansen, J. U.;

    1998-01-01

    A newly developed (off-line) spatial compound scanner was used to scan formalin-fixed atherosclerotic carotid plaques. Forty-eight B-mode images were recorded using 7 insonification angles. All calculations were done on the envelope-detected image data. The mean amplitude level (MAL) in (relative...

  17. Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.

    Science.gov (United States)

    Laplante, Marc-André; Charbonneau, Alexandre; Avramoglu, Rita Kohen; Pelletier, Patricia; Fang, Xiangping; Bachelard, Hélène; Ylä-Herttuala, Seppo; Laakso, Markku; Després, Jean-Pierre; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

    2013-09-01

    Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.

  18. The role of fecal calprotectin in investigating inflammatory bowel diseases

    OpenAIRE

    Mustafa Erbayrak; Cansel Turkay; Elife Eraslan; Hulya Cetinkaya; Benan Kasapoglu; Mehmet Bektas

    2009-01-01

    INTRODUCTION: Invasive and non-invasive tests can be used to evaluate the activity of inflammatory bowel diseases. OBJECTIVE: The aim of the present study was to investigate the role of fecal calprotectin in evaluating inflammatory bowel disease activity and the correlation of fecal calprotectin with the erythrocyte sedimentation rate and C reactive protein values in inflammatory bowel disease. METHOD: Sixty-five patients affected with inflammatory bowel disease were enrolled. Twenty outpatie...

  19. Cardiovascular and inflammatory effects of intratracheally instilled ambient dust from Augsburg, Germany, in spontaneously hypertensive rats (SHRs

    Directory of Open Access Journals (Sweden)

    Peters Annette

    2010-09-01

    exposure triggers low grade PM mediated inflammatory effects in the lungs but disturbs vascular homeostasis in pulmonary tissues and on a systemic level by affecting the renin angiotensin system, the endothelin system and the coagulation cascade. These findings are indicative for promotion of endothelial dysfunction, atherosclerotic lesions, and thrombogeneis and, thus, provide plausible evidence that susceptible-predisposed individuals may develop acute cardiac events like myocardial infarction when repeatedly exposed to high pollution episodes as observed in epidemiological studies in Augsburg, Germany.

  20. Chronic inflammatory demyelinating polyneuropathy

    Science.gov (United States)

    Polyneuropathy - chronic inflammatory; CIDP; Chronic inflammatory polyneuropathy; Guillain-Barré - CIDP ... CIDP is one cause of damage to nerves outside the brain or spinal cord ( peripheral neuropathy ). Polyneuropathy ...

  1. Autophagy in Atherosclerosis: A Phenomenon Found in Human Carotid Atherosclerotic Plaques

    Institute of Scientific and Technical Information of China (English)

    Huihui Liu; Yongjun Cao; Tong Tong; Jijun Shi; Yanlin Zhang; Yaping Yang; Chunfeng Liu

    2015-01-01

    Background:Autophagy has been found to be involved in animal and cell models ofatherosclerosis,but to date,it lacks general observation in human atherosclerotic plaques.Here,we investigated autophagy in smooth muscle cells (SMCs),endothelial cells (ECs),and macrophages in human atherosclerotic plaques via transmission electron microscopy (TEM),western blotting,and immunohistochemistry analysis.Methods:The histopathologic morphology of these plaques was observed via hematoxylin and eosin staining.The ultrastructural morphology of the SMCs,ECs,and macrophages in these plaques was observed via TEM.The localization ofmicrotubule-associated protein 1 light chain 3 (MAP 1-LC3),a relatively special maker ofautophagy,in plaques was observed by double fluorescent immunochemistty and western blotting.Results:All of these human atherosclerotic plaques were considered advanced and unstable in histologically observation.By double fluorescent immunochemistry,the expression of LC3-Ⅱ increased in the SMCs of the fibrous cap,the macrophages,and the microvascular ECs of the plaque shoulders.The protein level of LC3-Ⅱ by western blotting significantly increased in plaques compared with normal controls.In addition,TEM observation of plaques revealed certain features of autophagy in SMCs,ECs,and macrophages including the formation of myelin figures,vacuolization,and the accumulation of inclusions in the cytosol.These results indicate that autophagy is activated in SMCs,ECs,and macrophages in human advanced atherosclerotic plaques.Conclusions:Our study is to demonstrate the existence of autophagy in human atherosclerotic plaques by different methods,which may contribute to the development of pharmacological approaches to stabilize vulnerable and rupture-prone lesions.

  2. Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease

    Science.gov (United States)

    Tang, Jun

    Cardiovascular disease (CVD) is the leading cause of disease-related death in the world, accounting for 30 % global mortality. The majority of CVD is caused by atherosclerosis, a chronic inflammatory disease of major arteries featured by the deposition of lipids and cholesterol. Inflammation of atherosclerosis is mainly promoted by the pathological macrophages and monocytes, and modulating their functions has been proposed as a promising therapeutic target. This dissertation first presents the development of a novel simvastatin-loaded high-density lipoprotein (HDL) based nanoparticle ([S]-rHDL), which was able to deliver anti-inflammatory simvastatin preferentially to inflammatory monocytes in the blood and to macrophages in advanced atherosclerotic plaques, leading to the reduced inflammation in the tissue. Second, extensive in vivo characterization of [S]-rHDL in a mouse atherosclerosis model revealed that the anti-inflammatory capability of [S]-rHDL derived from its effects on blood monocytes, endothelial layer, monocyte recruitment, and plaque macrophage function. Third, a translational study that integrated the use of [S]-rHDL into oral statin treatment demonstrated a great potential for this nanomedicine as an attractive addition to the current high-dose oral statin standard-of-care for acute coronary syndrome. Finally, preliminary results suggested potential applications of the rHDL platform to other macrophage-implicated diseases.

  3. Inflammatory myofibroblastic tumor

    Directory of Open Access Journals (Sweden)

    Sangeeta Palaskar

    2011-01-01

    Full Text Available Inflammatory myofibroblastic tumor is an uncommon lesion of unknown cause. It encompasses a spectrum of myofibroblastic proliferation along with varying amount of inflammatory infiltrate. A number of terms have been applied to the lesion, namely, inflammatory pseudotumor, fibrous xanthoma, plasma cell granuloma, pseudosarcoma, lymphoid hamartoma, myxoid hamartoma, inflammatory myofibrohistiocytic proliferation, benign myofibroblatoma, and most recently, inflammatory myofibroblastic tumor. The diverse nomenclature is mostly descriptive and reflects the uncertainty regarding true biologic nature of these lesions. Recently, the concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and cytogenetic evidence of acquired clonal chromosomal abnormalities. We hereby report a case of inflammatory pseudotumor and review its inflammatory versus neoplastic behavior.

  4. Photoacoustic tomography to identify inflammatory arthritis

    Science.gov (United States)

    Rajian, Justin Rajesh; Girish, Gandikota; Wang, Xueding

    2012-09-01

    Identifying neovascularity (angiogenesis) as an early feature of inflammatory arthritis can help in early accurate diagnosis and treatment monitoring of this disease. Photoacoustic tomography (PAT) is a hybrid imaging modality which relies on intrinsic differences in the optical absorption among the tissues being imaged. Since blood has highly absorbing chromophores including both oxygenated and deoxygenated hemoglobin, PAT holds potential in identifying early angiogenesis associated with inflammatory joint diseases. PAT is used to identify changes in the development of inflammatory arthritis in a rat model. Imaging at two different wavelengths, 1064 nm and 532 nm, on rats revealed that there is a significant signal enhancement in the ankle joints of the arthritis affected rats when compared to the normal control group. Histology images obtained from both the normal and the arthritis affected rats correlated well with the PAT findings. Results support the fact that the emerging PAT could become a new tool for clinical management of inflammatory arthritis.

  5. Vascular endothelial growth factor (VEGF and monocyte chemoattractant protein (MCP-1 levels unaltered in symptomatic atherosclerotic carotid plaque patients from North India

    Directory of Open Access Journals (Sweden)

    Dheeraj eKhurana

    2013-04-01

    Full Text Available We aimed to identify the role of vascular endothelial growth factor(VEGF and monocyte chemoattractant protein(MCP-1 as a serum biomarker of symptomatic carotid atherosclerotic plaque in North Indian population. Individuals with symptomatic carotid atherosclerotic plaque have high risk of ischemic stroke. Previous studies from western countries have shown an association between VEGF and MCP-1 levels and the incidence of ischemic stroke. In this study, venous blood from 110 human subjects was collected, 57 blood samples of which were obtained from patients with carotid plaques, 38 neurological controls without carotid plaques and another 15 healthy controls who had no history of serious illness. Serum VEGF and MCP-1 levels were measured using commercially available enzyme-linked immunosorbent assay(ELISA. We also correlated the data clinically and carried out risk factor analysis based on the detailed questionnaire obtained from each patient. For risk factor analysis, a total of 70 symptomatic carotid plaque cases and equal number of age and sex matched healthy controls were analyzed. We found that serum VEGF levels in carotid plaque patients did not show any significant change when compared to either of the controls. Similarly, there was no significant upregulation of monocyte chemoattractant protein-1 in the serum of these patients. The risk factor analysis revealed that hypertension, diabetes, and physical inactivity were the main correlates of carotid atherosclerosis(p<0.05. Prevalence of patients was higher residing in urban areas as compared to rural region. We also found that patients coming from mountaineer region were relatively less vulnerable to cerebral atherosclerosis as compared to the ones residing at plain region. We conclude that the pathogenesis of carotid plaques may progress independent of these inflammatory molecules. In parallel, risk factor analysis indicates hypertension, diabetes and sedentary lifestyle as the most

  6. Depressive symptom clusters are differentially associated with atherosclerotic disease

    NARCIS (Netherlands)

    Bus, B. A. A.; Marijnissen, R. M.; Holewijn, S.; Franke, B.; Purandare, N.; de Graaf, J.; den Heijer, M.; Buitelaar, J. K.; Voshaar, R. C. Oude

    2011-01-01

    Background. Depression increases the risk of subsequent vascular events in both cardiac and non-cardiac patients. Atherosclerosis, the underlying process leading to vascular events, has been associated with depression. This association, however, may be confounded by the somatic-affective symptoms be

  7. David M. Hume memorial lecture. In situ vein bypass in the treatment of femoropopliteal atherosclerotic disease: a ten year study.

    Science.gov (United States)

    Hall, K V; Rostad, H

    1978-08-01

    The in situ vein bypass technic for femoropopliteal atherosclerotic disease is described. Several factors influence the long-term results, the most important being a history of myocardial disease, the size of the vein graft, and sufficient runoff.

  8. Insulin resistance, small LDL particles, and risk for atherosclerotic disease.

    Science.gov (United States)

    Toth, Peter P

    2014-01-01

    There is a global epidemic of obesity, metabolic syndrome, and diabetes mellitus. Insulin resistance (IR) is etiologic for both metabolic syndrome and diabetes mellitus. IR induces a broad range of toxic systemic effects, including dyslipidemia, hypertension, hyperglycemia, increased production of advanced glycosylation end products, increased inflammatory tone, as well as a prothrombotic and pro-oxidative state. Patients with IR are highly vulnerable to the development of accelerated atherosclerosis as well its clinical sequelae, including coronary artery disease and myocardial infarction, carotid artery disease and ischemic stroke, peripheral arterial disease and claudication/lower extremity amputation, and coronary mortality. Among the most important risk factors patients afflicted with IR develop is the so-called atherogenic lipid triad: large numbers of small, dense low-density lipoprotein (sdLDL) particles, hypertriglyceridemia, and low serum concentrations of high-density lipoprotein cholesterol. Though controversial, much recent evidence suggests that the formation of sdLDL particles in the setting of IR is an important metabolic transition. Some studies suggest that these smaller particles are more atherogenic than their larger, more buoyant counterparts. At least part of the explanation for the apparent augmented atherogenicity of small LDL particles is their reduced systemic clearance by the LDL receptor, increased vulnerability to oxidation rendering them more apt for scavenging by macrophages, and possible increased flux into the subendothelial space of arterial walls. Numerous small studies suggest that sdLDL is highly correlated with cardiovascular events. Cardiovascular medicine is in need of a large prospective, randomized study that would more definitively investigate the impact of small, dense LDL (sdLDL) on risk for cardiovascular disease and whether therapeutic interventions designed to specifically reduce the burden of sdLDL are associated

  9. Delivery of negatively charged liposomes into the atherosclerotic plaque of apolipoprotein E-deficient mouse aortic tissue

    OpenAIRE

    Zhaorigetu, Siqin; Rodriguez-Aguayo, Cristian; Sood, Anil K.; Lopez-Berestein, Gabriel; Walton, Brian L.

    2014-01-01

    Liposomes have been used to diagnose and treat cancer and, to a lesser extent, cardiovascular disease. We previously showed the uptake of anionic liposomes into the atheromas of Watanabe heritable hyperlipidemic rabbits within lipid pools. However, the cellular distribution of anionic liposomes in atherosclerotic plaque remains undescribed. In addition, how anionic liposomes are absorbed into atherosclerotic plaque is unclear. We investigated the uptake and distribution of anionic liposomes i...

  10. Prevalence of Foam Cells and Helper-T cells in Atherosclerotic Plaques of Korean Patients with Carotid Atheroma

    OpenAIRE

    Lee, Won-Ha; Ko, Young-Hyeh; Kim, Dong-Ik; Lee, Byung-Boong; Park, Jeong-Euy

    2000-01-01

    Background Inflammation and activation of immune cells have important roles in the pathogenesis of atherosclerosis. We analyzed the involvement of various immune cells in the pathogenesis of atherosclerosis. Methods We investigated the presence of foam cells, lymphocytes and killer cells in 11 atherosclerotic plaque specimens removed from Korean patients who underwent carotid endoarterectomy. Atherosclerotic plaques were analyzed by immunohistochemistry using monoclonal antibody specific to f...

  11. Rosiglitazone modulates collagen deposition and metabolism in atherosclerotic plaques of fat-fed ApoE-knockout mice

    OpenAIRE

    Zhou, Mingxue; Xu, Hao; Liu, Weihong; Liu, Hongxu

    2015-01-01

    Abnormal collagen deposition, as well as collagen metabolism, plays a crucial role in the formation and progression of vulnerable atherosclerotic plaques (VAPs), which are susceptible to rupture. According to our previous findings, rosiglitazone, a thiazolidinedione, can promote the stability of atherosclerotic plaques in fat-fed ApoE-knockout mice; however, it is unknown whether it can modulate collagen deposition and metabolism in VAPs. The present study was designed to determine the effect...

  12. The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation

    Science.gov (United States)

    Cuff, Carolyn A.; Kothapalli, Devashish; Azonobi, Ijeoma; Chun, Sam; Zhang, Yuanming; Belkin, Richard; Yeh, Christine; Secreto, Anthony; Assoian, Richard K.; Rader, Daniel J.; Puré, Ellen

    2001-01-01

    Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice. We found a 50–70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates. We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions. Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the “synthetic” state as measured by expression of VCAM-1. Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation. We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms. PMID:11581304

  13. 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...

  14. 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...... 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......), II) samples are weighted by the local contour distance of the lumen and outer wall between histology and in vivo data, and III) 10% of each class is rejected by Gaussian outlier rejection. Classification was evaluated on the relative volumes (% of tissue type in the vessel wall) for calcified...

  15. Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Dong Ju Son

    2014-08-01

    Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

  16. Nuclear medicine and coronary artery disease: evaluation of tracers of myocardial perfusion and vulnerable atherosclerotic plaque

    International Nuclear Information System (INIS)

    Coronary artery disease is one of the primary cause of mortality worldwide. Nuclear medicine is the major imaging technique for diagnosis and following of this disease. perfusion: nowadays, major radioactive agents used in clinical practice are myocardial perfusion tracers. The reference tracer is thallium-201. However, 201Tl presents some drawbacks. 99mTcn-noet has been proposed for its replacement. This study shows that in contrast with previous studies realized in vitro on cardio myocytes, verapamil, an l-type calcium channel inhibitor, does not inhibit myocardial fixation of 99mTcn-noet in vivo in dog. This data is in agreement with the hypothesis of a non specific endothelial fixation of this tracer. Moreover, this study shows that as a pure tracer of myocardial perfusion, 99mTcn-noet can also be used to assess myocardial viability on a model of myocardial chronic infarction in rat. atherosclerosis: disruption of vulnerable atherosclerotic plaques is the main event leading to coronary accidents. The second part of this study concerns the evaluation of new potential tracers of the vulnerable atherosclerotic plaque in an experimental model of rabbit with an inheritable hypercholesterolemia. The four tracers evaluated (b2702(r), b2702-I, b2702-Tc and Tc-raft-b2702) are synthetic peptides comprising the residues 75-84 of hla-b2702, a molecule known to link vcam-1, an adhesion molecule expressed in vulnerable atherosclerotic plaque. The autoradiography studies show that all tracers accumulate within atherosclerotic plaque expressing vcam- and that. i-b2702 shows the best plaque/control fixation ratio. (author)

  17. Advances in immune-modulating therapies to treat atherosclerotic cardiovascular diseases

    OpenAIRE

    Chyu, Kuang-Yuh; Prediman K Shah

    2014-01-01

    In addition to hypercholesterolemia, innate and adaptive immune mechanisms play a critical role in atherogenesis, thus making immune-modulation therapy a potentially attractive way of managing atherosclerotic cardiovascular disease. These immune-modulation strategies include both active and passive immunization and confer beneficial reduction in atherosclerosis. Preclinical studies have demonstrated promising results and we review current knowledge on the complex role of the immune system and...

  18. Assessment of normal and atherosclerotic arterial wall thickness with an intravascular ultrasound imaging catheter.

    OpenAIRE

    Mallery, JA; Tobis, JM; Griffith, J.; Gessert, J; McRae, M; Moussabeck, O; Bessen, M; Moriuchi, M; Henry, WL

    1990-01-01

    A prototype intravascular ultrasound imaging catheter with a 20 MHz transducer was used to obtain 59 cross-sectional images in 14 segments of human atherosclerotic arteries. Three distinct components of the arterial wall were visualized on the ultrasound images: a highly reflective intima, an echolucent media, and a moderately reflective adventitia. Images were obtained at 1 mm increments in vitro and were compared with histologic sections at the same levels. Measurements of the arterial laye...

  19. Sodium-Glucose Cotransporter 2 Inhibitors: Possible Anti-Atherosclerotic Effects Beyond Glucose Lowering

    OpenAIRE

    Yanai, Hidekatsu; Katsuyama, Hisayuki; Hamasaki, Hidetaka; Adachi, Hiroki; Moriyama, Sumie; Yoshikawa, Reo; Sako, Akahito

    2015-01-01

    The new drug for type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, is reversible inhibitor of SGLT-2, leading to reduction of renal glucose reabsorption and decrease of plasma glucose, in an insulin-independent manner. In addition to glucose control, the management of coronary risk factors is very important for patients with diabetes. Here we reviewed published articles about the possible anti-atherosclerotic effects beyond glucose lowering of the SGLT-2 inhibitors. We s...

  20. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice

    OpenAIRE

    Zhao, Yang; Dai, Xiao-Yan; Zhou, Zhou; Zhao, Ge-xin; Wang, Xian; Xu, Ming-Jiang

    2015-01-01

    Aim: Recent evidence suggests that the essential amino acid leucine may be involved in systemic cholesterol metabolism. In this study, we investigated the effects of leucine supplementation on the development of atherosclerosis in apoE null mice. Methods: ApoE null mice were fed with chow supplemented with leucine (1.5% w/v) in drinking water for 8 week. Aortic atherosclerotic lesions were examined using Oil Red O staining. Plasma lipoprotein-cholesterol levels were measured with fast protein...

  1. Elevated sodium and dehydration stimulate inflammatory signaling in endothelial cells and promote atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Natalia I Dmitrieva

    Full Text Available Cardiovascular diseases (CVDs are a leading health problem worldwide. Epidemiologic studies link high salt intake and conditions predisposing to dehydration such as low water intake, diabetes and old age to increased risk of CVD. Previously, we demonstrated that elevation of extracellular sodium, which is a common consequence of these conditions, stimulates production by endothelial cells of clotting initiator, von Willebrand Factor, increases its level in blood and promotes thrombogenesis. In present study, by PCR array, using human umbilical vein endothelial cells (HUVECs, we analyzed the effect of high NaCl on 84 genes related to endothelial cell biology. The analysis showed that the affected genes regulate many aspects of endothelial cell biology including cell adhesion, proliferation, leukocyte and lymphocyte activation, coagulation, angiogenesis and inflammatory response. The genes whose expression increased the most were adhesion molecules VCAM1 and E-selectin and the chemoattractant MCP-1. These are key participants in the leukocyte adhesion and transmigration that play a major role in the inflammation and pathophysiology of CVD, including atherosclerosis. Indeed, high NaCl increased adhesion of mononuclear cells and their transmigration through HUVECs monolayers. In mice, mild water restriction that elevates serum sodium by 5 mmol/l, increased VCAM1, E-selectin and MCP-1 expression in mouse tissues, accelerated atherosclerotic plaque formation in aortic root and caused thickening or walls of coronary arteries. Multivariable linear regression analysis of clinical data from the Atherosclerosis Risk in Communities Study (n=12779 demonstrated that serum sodium is a significant predictor of 10 Years Risk of coronary heart disease. These findings indicate that elevation of extracellular sodium within the physiological range is accompanied by vascular changes that facilitate development of CVD. The findings bring attention to serum sodium as a

  2. Inflammatory myofibroblastic tumour of maxilla

    Directory of Open Access Journals (Sweden)

    Deshingkar S

    2007-01-01

    Full Text Available Inflammatory myofibroblastic tumour (IMT is a biologically controversial entity that was originally described as non-neoplastic lesion in the lungs and designated initially as inflammatory pseudotumour. The lesion has recently been recognized to occur at various sites but rarely affects head and neck region. Controversies still exist regarding its reactive versus neoplastic nature. The lesion has a potential for recurrence, persistent local growth, progression to frank sarcoma and metastasis. Hence IMT can best be regarded as a low-grade sarcoma. A case of a 30-year-old female with swelling in the right maxilla and associated ophthalmic manifestations is discussed here. Contribution of immunohistochemistry for diagnosis of IMT is emphasized. Additional cytogenetic studies of this highly enigmatic and minimally studied tumour are warranted.

  3. Inflammatory pseudotumour of the maxilla.

    Science.gov (United States)

    Kichenaradjou, A; Barrett, A W; Norris, P; Rowell, N; Newman, L

    2016-09-01

    Inflammatory pseudotumour (IP), also known as inflammatory myofibroblastic tumour (IMT), is a rare lesion of the maxillofacial skeleton and a diagnosis by exclusion. We describe three cases which affected the maxilla, two women and one man of ages 67, 56 and 70 years at presentation. All showed the typical, rather non-specific histopathological features. IgG4-positive plasma cells varied greatly in prominence, and none of the three lesions expressed ALK-1. Both women responded to steroids and radiotherapy, though one also required azathioprine. Despite maxillectomy, radiotherapy, steroids and cyclophosphamide, the man suffered intracranial spread and succumbed to persistent disease. The cases described here demonstrate the clinicopathological difficulties presented by this entity and its aggressive, unpredictable behaviour. PMID:27052813

  4. Endogenous Bioactive Peptides as Potential Biomarkers for Atherosclerotic Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Tsutomu Hirano

    2012-04-01

    Full Text Available Cardiovascular disease is the leading cause of death worldwide, with high medical costs and rates of disability. It is therefore important to evaluate the use of cardiovascular biomarkers in the early diagnosis of coronary artery disease (CAD. We have screened a variety of recently identified bioactive peptides candidates in anticipation that they would allow detection of atherosclerotic CAD. Especially, we have focused on novel anti-atherogenic peptides as indicators and negative risk factors for CAD. In vitro, in vivo and clinical studies indicated that human adiponectin, heregulin-β1, glucagon-like peptide-1 (GLP-1, and salusin-α, peptides of 244, 71, 30, and 28 amino acids, respectively, attenuate the development and progression of atherosclerotic lesions by suppressing macrophage foam cell formation via down-regulation of acyl-coenzyme A: cholesterol acyltransferase-1. Circulating levels of these peptides in the blood are significantly decreased in patients with CAD compared to patients without CAD. Receiver operating characteristic analyses showed that salusin-α is a more useful biomarker, with better sensitivity and specificity, compared with the others for detecting CAD. Therefore, salusin-α, heregulin-β1, adiponectin, and/or GLP-1, alone or in various combinations, may be useful as biomarkers for atherosclerotic CAD.

  5. Detecting microcalcifications in atherosclerotic plaques by a simple trichromic staining method for epoxy embedded carotid endarterectomies

    Science.gov (United States)

    Relucenti, M.; Heyn, R.; Petruzziello, L.; Pugliese, G.; Taurino, M.; Familiari, G.

    2010-01-01

    Atherosclerotic plaques have a high probability of undergoing rapid progression to stenosis, becoming responsible of acute coronary syndrome or stroke. Microcalcifications may act as enhancers of atherosclerotic plaque vulnerability. Considering that calcifications with a diameter smalller than 10 µm in paraffin embedded tissue are rather difficult to detect, our aim was to analyze microcalcifications on semithin sections from epoxy resin embedded samples of carotid endarterectomies using an original trichromic stain (methylene blue-azur B - basic fuchsine - alizarin red). We have compared samples stained either with our method, methylene blue-azur B alone or with Von Kossa staining, and methylene blue-azur B -basic fuchsine alone or with Von Kossa staining. Our method resulted to be simple and fast (ca. 2 min), it gives a sharp general contrast for all structures and allows to easy identify collagen and elastin. In addition, gray-green colour associated to intracellular lipid droplets evidences foam cells, which are particularly abundant in endarterectomies samples. Mast cells and their metachromatic granules are also well recognized. Calcifications over 0,5 µm are clearly recognizable. In conclusion, microcalcifications are clearly distinguished from the extracellular matrix in spite of their reduced dimensions. Methylene blue-azur B-basic fuchsine-alizarin red method is easy to use, reproducible, and is particularly suitable for the identification of microcalcifications in the morphological analysis of atherosclerotic plaques. PMID:20819772

  6. Detecting microcalcifications in atherosclerotic plaques by a simple trichromic staining method for epoxy embedded carotid endarterectomies

    Directory of Open Access Journals (Sweden)

    G. Familiari

    2010-09-01

    Full Text Available Atherosclerotic plaques have a high probability of undergoing rapid progression to stenosis, becoming responsible of acute coronary syndrome or stroke. Microcalcifications may act as enhancers of atherosclerotic plaque vulnerability. Considering that calcifications with a diameter smalller than 10 mm in paraffin embedded tissue are rather difficult to detect, our aim was to analyze microcalcifications on semithin sections from epoxy resin embedded samples of carotid endarterectomies using an original trichromic stain (methylene blue- azur B - basic fuchsine - alizarin red. We have compared samples stained either with our method, methylene blue-azur B alone or with Von Kossa staining, and methylene blue-azur B -basic fuchsine alone or with Von Kossa staining. Our method resulted to be simple and fast (ca. 2 min, it gives a sharp general contrast for all structures and allows to easy identify collagen and elastin. In addition, gray-green colour associated to intracellular lipid droplets evidences foam cells, which are particularly abundant in endarterectomies samples. Mast cells and their metachromatic granules are also well recognized. Calcifications over 0,5 mm are clearly recognizable. In conclusion, microcalcifications are clearly distinguished from the extracellular matrix in spite of their reduced dimensions. Methylene blue-azur B-basic fuchsine-alizarin red method is easy to use, reproducible, and is particularly suitable for the identification of microcalcifications in the morphological analysis of atherosclerotic plaques.

  7. Influence of particle size on the distributions of liposomes to atherosclerotic lesions in mice.

    Science.gov (United States)

    Chono, Sumio; Tauchi, Yoshihiko; Morimoto, Kazuhiro

    2006-01-01

    In order to confirm the efficacy of liposomes as a drug carrier for atherosclerotic therapy, the influence of particle size on the distribution of liposomes to atherosclerotic lesions in mice was investigated. In brief, liposomes of three different particle sizes (500, 200, and 70 nm) were prepared, and the uptake of liposomes by the macrophages and foam cells in vitro and the biodistributions of liposomes administered intravenously to atherogenic mice in vivo were examined. The uptake by the macrophages and foam cells increased with the increase in particle size. Although the elimination rate from the blood circulation and the hepatic and splenic distribution increased with the increase in particle size in atherogenic mice, the aortic distribution was independent of the particle size. The aortic distribution of 200 nm liposomes was the highest in comparison with the other sizes. Surprisingly, the aortic distribution of liposomes in vivo did not correspond with the uptake by macrophages and foam cells in vitro. These results suggest that there is an optimal size for the distribution of liposomes to atherosclerotic lesions.

  8. Atherosclerotic cardiovascular disease risk and evidence-based management of cholesterol

    Directory of Open Access Journals (Sweden)

    Satyajeet Roy

    2014-01-01

    Full Text Available An elevated level of low-density lipoprotein cholesterol is directly associated with development of atherosclerotic cardiovascular disease, which may present as coronary heart disease, stroke, and peripheral arterial disease. The new cholesterol management guidelines from the American College of Cardiology and the American Heart Association aim to address a comprehensive approach to prevent and reduce the risk of atherosclerotic cardiovascular disease. The new guidelines recommend initiation of heart healthy lifestyle modifications and 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor ("statin" therapy in individuals who are at a high risk for atherosclerotic cardiovascular disease. It is estimated that these guidelines could result in "statin" therapy for one in every three adults in the United States. This article presents a review of the current cholesterol management guidelines, recommendations from relevant randomized controlled trials and meta-analyses obtained from the searches in Medline/PubMed and Cochrane Database of Systematic Reviews, and publications from the Centers for Disease Control and Prevention, the Centers for Medicare and Medicaid Service, and the United States Preventive Services Task Force.

  9. 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.

  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. Effect of Watermarking on Diagnostic Preservation of Atherosclerotic Ultrasound Video in Stroke Telemedicine.

    Science.gov (United States)

    Dey, Nilanjan; Bose, Soumyo; Das, Achintya; Chaudhuri, Sheli Sinha; Saba, Luca; Shafique, Shoaib; Nicolaides, Andrew; Suri, Jasjit S

    2016-04-01

    Embedding of diagnostic and health care information requires secure encryption and watermarking. This research paper presents a comprehensive study for the behavior of some well established watermarking algorithms in frequency domain for the preservation of stroke-based diagnostic parameters. Two different sets of watermarking algorithms namely: two correlation-based (binary logo hiding) and two singular value decomposition (SVD)-based (gray logo hiding) watermarking algorithms are used for embedding ownership logo. The diagnostic parameters in atherosclerotic plaque ultrasound video are namely: (a) bulb identification and recognition which consists of identifying the bulb edge points in far and near carotid walls; (b) carotid bulb diameter; and (c) carotid lumen thickness all along the carotid artery. The tested data set consists of carotid atherosclerotic movies taken under IRB protocol from University of Indiana Hospital, USA-AtheroPoint™ (Roseville, CA, USA) joint pilot study. ROC (receiver operating characteristic) analysis was performed on the bulb detection process that showed an accuracy and sensitivity of 100 % each, respectively. The diagnostic preservation (DPsystem) for SVD-based approach was above 99 % with PSNR (Peak signal-to-noise ratio) above 41, ensuring the retention of diagnostic parameter devalorization as an effect of watermarking. Thus, the fully automated proposed system proved to be an efficient method for watermarking the atherosclerotic ultrasound video for stroke application.

  12. A Proteomic Focus on the Alterations Occurring at the Human Atherosclerotic Coronary Intima*

    Science.gov (United States)

    de la Cuesta, Fernando; Alvarez-Llamas, Gloria; Maroto, Aroa S.; Donado, Alicia; Zubiri, Irene; Posada, Maria; Padial, Luis R.; Pinto, Angel G.; Barderas, Maria G.; Vivanco, Fernando

    2011-01-01

    Coronary atherosclerosis still represents the major cause of mortality in western societies. Initiation of atherosclerosis occurs within the intima, where major histological and molecular changes are produced during pathogenesis. So far, proteomic analysis of the atherome plaque has been mainly tackled by the analysis of the entire tissue, which may be a challenging approach because of the great complexity of this sample in terms of layers and cell type composition. Based on this, we aimed to study the intimal proteome from the human atherosclerotic coronary artery. For this purpose, we analyzed the intimal layer from human atherosclerotic coronaries, which were isolated by laser microdissection, and compared with those from preatherosclerotic coronary and radial arteries, using a two-dimensional Differential-In-Gel-Electrophoresis (DIGE) approach. Results have pointed out 13 proteins to be altered (seven up-regulated and six down-regulated), which are implicated in the migrative capacity of vascular smooth muscle cells, extracellular matrix composition, coagulation, apoptosis, heat shock response, and intraplaque hemorrhage deposition. Among these, three proteins (annexin 4, myosin regulatory light 2, smooth muscle isoform, and ferritin light chain) constitute novel atherosclerotic coronary intima proteins, because they were not previously identified at this human coronary layer. For this reason, these novel proteins were validated by immunohistochemistry, together with hemoglobin and vimentin, in an independent cohort of arteries. PMID:21248247

  13. A proteomic focus on the alterations occurring at the human atherosclerotic coronary intima.

    Science.gov (United States)

    de la Cuesta, Fernando; Alvarez-Llamas, Gloria; Maroto, Aroa S; Donado, Alicia; Zubiri, Irene; Posada, Maria; Padial, Luis R; Pinto, Angel G; Barderas, Maria G; Vivanco, Fernando

    2011-04-01

    Coronary atherosclerosis still represents the major cause of mortality in western societies. Initiation of atherosclerosis occurs within the intima, where major histological and molecular changes are produced during pathogenesis. So far, proteomic analysis of the atherome plaque has been mainly tackled by the analysis of the entire tissue, which may be a challenging approach because of the great complexity of this sample in terms of layers and cell type composition. Based on this, we aimed to study the intimal proteome from the human atherosclerotic coronary artery. For this purpose, we analyzed the intimal layer from human atherosclerotic coronaries, which were isolated by laser microdissection, and compared with those from preatherosclerotic coronary and radial arteries, using a two-dimensional Differential-In-Gel-Electrophoresis (DIGE) approach. Results have pointed out 13 proteins to be altered (seven up-regulated and six down-regulated), which are implicated in the migrative capacity of vascular smooth muscle cells, extracellular matrix composition, coagulation, apoptosis, heat shock response, and intraplaque hemorrhage deposition. Among these, three proteins (annexin 4, myosin regulatory light 2, smooth muscle isoform, and ferritin light chain) constitute novel atherosclerotic coronary intima proteins, because they were not previously identified at this human coronary layer. For this reason, these novel proteins were validated by immunohistochemistry, together with hemoglobin and vimentin, in an independent cohort of arteries. PMID:21248247

  14. EPA and DHA exposure alters the inflammatory response but not the surface expression of toll-like receptor 4 in macrophages

    OpenAIRE

    Honda, Kaori L.; Lamon-Fava, Stefania; Matthan, Nirupa R.; Wu, Dayong; Lichtenstein, Alice H

    2014-01-01

    Dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and their respective enrichment in cell membranes have been negatively associated with atherosclerotic lesion development. This effect may be mediated, in part, by dampened inflammatory response of macrophages triggered by toll-like receptor 4 (TLR4) activation. This study investigated the influence of membrane fatty acid profile on TLR4-mediated inflammation in RAW 264.7 macrophages. Cells pretreated with myristic a...

  15. Chronic Internal Exposure to Low Dose 137Cs Induces Positive Impact on the Stability of Atherosclerotic Plaques by Reducing Inflammation in ApoE-/- Mice

    Science.gov (United States)

    Le Gallic, Clélia; Phalente, Yohann; Manens, Line; Dublineau, Isabelle; Benderitter, Marc; Gueguen, Yann; Lehoux, Stephanie; Ebrahimian, Teni G.

    2015-01-01

    After Chernobyl and Fukushima Daï Chi, two major nuclear accidents, large amounts of radionuclides were released in the environment, mostly caesium 137 (137Cs). Populations living in contaminated territories are chronically exposed to radionuclides by ingestion of contaminated food. However, questions still remain regarding the effects of low dose ionizing radiation exposure on the development and progression of cardiovascular diseases. We therefore investigated the effects of a chronic internal exposure to 137Cs on atherosclerosis in predisposed ApoE-/- mice. Mice were exposed daily to 0, 4, 20 or 100 kBq/l 137Cs in drinking water, corresponding to range of concentrations found in contaminated territories, for 6 or 9 months. We evaluated plaque size and phenotype, inflammatory profile, and oxidative stress status in different experimental groups. Results did not show any differences in atherosclerosis progression between mice exposed to 137Cs and unexposed controls. However, 137Cs exposed mice developed more stable plaques with decreased macrophage content, associated with reduced aortic expression of pro-inflammatory factors (CRP, TNFα, MCP-1, IFNγ) and adhesion molecules (ICAM-1, VCAM-1 and E-selectin). Lesions of mice exposed to 137Cs were also characterized by enhanced collagen and smooth muscle cell content, concurrent with reduced matrix metalloproteinase MMP8 and MMP13 expression. These results suggest that low dose chronic exposure of 137Cs in ApoE-/- mice enhances atherosclerotic lesion stability by inhibiting pro-inflammatory cytokine and MMP production, resulting in collagen-rich plaques with greater smooth muscle cell and less macrophage content. PMID:26046630

  16. Chronic Internal Exposure to Low Dose 137Cs Induces Positive Impact on the Stability of Atherosclerotic Plaques by Reducing Inflammation in ApoE-/- Mice.

    Directory of Open Access Journals (Sweden)

    Clélia Le Gallic

    Full Text Available After Chernobyl and Fukushima Daï Chi, two major nuclear accidents, large amounts of radionuclides were released in the environment, mostly caesium 137 (137Cs. Populations living in contaminated territories are chronically exposed to radionuclides by ingestion of contaminated food. However, questions still remain regarding the effects of low dose ionizing radiation exposure on the development and progression of cardiovascular diseases. We therefore investigated the effects of a chronic internal exposure to 137Cs on atherosclerosis in predisposed ApoE-/- mice. Mice were exposed daily to 0, 4, 20 or 100 kBq/l 137Cs in drinking water, corresponding to range of concentrations found in contaminated territories, for 6 or 9 months. We evaluated plaque size and phenotype, inflammatory profile, and oxidative stress status in different experimental groups. Results did not show any differences in atherosclerosis progression between mice exposed to 137Cs and unexposed controls. However, 137Cs exposed mice developed more stable plaques with decreased macrophage content, associated with reduced aortic expression of pro-inflammatory factors (CRP, TNFα, MCP-1, IFNγ and adhesion molecules (ICAM-1, VCAM-1 and E-selectin. Lesions of mice exposed to 137Cs were also characterized by enhanced collagen and smooth muscle cell content, concurrent with reduced matrix metalloproteinase MMP8 and MMP13 expression. These results suggest that low dose chronic exposure of 137Cs in ApoE-/- mice enhances atherosclerotic lesion stability by inhibiting pro-inflammatory cytokine and MMP production, resulting in collagen-rich plaques with greater smooth muscle cell and less macrophage content.

  17. Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer.

    Science.gov (United States)

    Connelly, Margery A; Gruppen, Eke G; Otvos, James D; Dullaart, Robin P F

    2016-08-01

    The physiological function initially attributed to the oligosaccharide moieties or glycans on inflammatory glycoproteins was to improve protein stability. However, it is now clear that glycans play a prominent role in glycoprotein structure and function and in some cases contribute to disease states. In fact, glycan processing contributes to pathogenicity not only in autoimmune disorders but also in atherosclerotic cardiovascular disease, diabetes and malignancy. While most clinical laboratory tests measure circulating levels of inflammatory proteins, newly developed diagnostic and prognostic tests are harvesting the information that can be gleaned by measuring the amount or structure of the attached glycans, which may be unique to individuals as well as various diseases. As such, these newer glycan-based tests may provide future means for more personalized approaches to patient stratification and improved patient care. Here we will discuss recent progress in high-throughput laboratory methods for glycomics (i.e. the study of glycan structures) and glycoprotein quantification by methods such as mass spectrometry and nuclear magnetic resonance spectroscopy. We will also review the clinical utility of glycoprotein and glycan measurements in the prediction of common low-grade inflammatory disorders including cardiovascular disease, diabetes and cancer, as well as for monitoring autoimmune disease activity. PMID:27312321

  18. The Renin-Angiotensin System Modulates Inflammatory Processes in Atherosclerosis: Evidence from Basic Research and Clinical Studies

    Directory of Open Access Journals (Sweden)

    Fabrizio Montecucco

    2009-01-01

    Full Text Available Recent evidence shows that the renin-angiotensin system is a crucial player in atherosclerotic processes. The regulation of arterial blood pressure was considered from its first description of the main mechanism involved. Vasoconstriction (mediated by angiotensin II and salt and water retention (mainly due to aldosterone were classically considered as pivotal proatherosclerotic activities. However, basic research and animal studies strongly support angiotensin II as a proinflammatory mediator, which directly induces atherosclerotic plaque development and heart remodeling. Furthermore, angiotensin II induces proatherosclerotic cytokine and chemokine secretion and increases endothelial dysfunction. Accordingly, the pharmacological inhibition of the renin-angiotensin system improves prognosis of patients with cardiovascular disease even in settings of normal baseline blood pressure. In the present review, we focused on angiotensin-convertingenzyme (ACE inhibitors, angiotensin II receptor blockers (ARBs, and renin inhibitors to update the direct activities of the renin-angiotensin system in inflammatory processes governing atherosclerosis.

  19. Imaging of inflamed carotid artery atherosclerotic plaques with the use of {sup 99m}Tc-HYNIC-IL-2 scintigraphy in end-stage renal disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Opalinska, Marta; Pach, Dorota; Sowa-Staszczak, Anna; Glowa, Boguslaw; Hubalewska-Dydejczyk, Alicja [Jagiellonian University Medical School, Nuclear Medicine Unit, Department of Endocrinology, Cracow (Poland); Stompor, Tomasz [University of Warmia and Mazury in Olsztyn, Department of Nephrology, Hypertensiology and Internal Medicine, Faculty of Medicine, Olsztyn (Poland); Mikolajczak, Renata; Garnuszek, Piotr; Maurin, Michal; Karczmarczyk, Urszula [National Centre for Nuclear Research Radioisotope Centre POLATOM, Otwock (Poland); Fedak, Danuta [Jagiellonian University Medical School, Clinical Biochemistry, Cracow (Poland); Krzanowski, Marcin; Sulowicz, Wladyslaw [Jagiellonian University Medical School, Department of Nephrology, Cracow (Poland); Rakowski, Tomasz [Jagiellonian University Medical School, 2nd Department of Cardiology, Institute of Cardiology, Cracow (Poland)

    2012-04-15

    Identification of vulnerable plaques remains crucial for better cardiovascular risk assessment. At least 20% of inflammatory cells within unstable (vulnerable) plaques comprise T lymphocytes, which contain receptors for interleukin-2 (IL-2); those receptors can be identified by scintigraphy with radiolabelled IL-2.The aim of this study was to identify the ''inflamed'' (vulnerable) plaques by scintigraphy using IL-2 labelled with {sup 99m}Tc in the selected, high cardiovascular risk group of end-stage renal disease (ESRD) patients. A total of 28 patients (18 men, 10 women, aged 55.2 {+-} 9.6 years, 17 on peritoneal dialysis, 11 on haemodialysis) underwent common carotid artery (CCA) scintigraphy with the use of {sup 99m}Tc-hydrazinonicotinamide (HYNIC)-IL-2. In all cases, ultrasound examination of the CCA was performed and levels of selected proinflammatory factors, atherogenic markers and calcium-phosphate balance parameters were measured. Finally, the target to non-target (T/nT) ratio of IL-2 uptake in atherosclerotic plaques with intima-media thickness (IMT), classic cardiovascular risk factors and concentrations of the measured factors were compared. Increased {sup 99m}Tc-HYNIC-IL-2 uptake in atherosclerotic plaques in 38/41 (91%) cases was detected. The median T/nT ratio of focal {sup 99m}Tc-HYNIC-IL-2 uptake in atherosclerotic plaques was 2.35 (range 1.23-3.63). The mean IMT value on the side of plaques assessed by scintigraphy was 0.79 {+-} 0.18 mm (median 0.8, range 0.5-1.275). Correlations between T/nT ratio and homocysteine (R = 0.22, p = 0.037), apolipoprotein B (apoB) (R = 0.31, p = 0.008), apoB to apoA-I ratio (R = 0.29, p = 0.012) and triglyceride concentration (R = 0.26, p = 0.021) were detected. A lower T/nT ratio in patients with better parameters of nutritional status (haemoglobin, albumin, adiponectin) in comparison with patients with worse nutritional parameters (3.20 {+-} 0.5 vs 2.16 {+-} 0.68, p = 0.025) was revealed as well

  20. Chronic Inflammatory Demyelinating Polyneuropathy

    OpenAIRE

    Dimachkie, Mazen M.; Barohn, Richard J.

    2013-01-01

    Chronic Inflammatory polyneuropathies are an important group of neuromuscular disorders that present chronically and progress over more than 8 weeks, being referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). Despite tremendous progress in elucidating disease pathogenesis, the exact triggering event remains unknown. Our knowledge regarding diagnosis and management of CIDP and its variants continues to expand, resulting in improved opportunities for identification and treat...

  1. Curcumin in inflammatory diseases.

    Science.gov (United States)

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. PMID:23281076

  2. Pediatric inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Karen A Diefenbach; Christopher K Breuer

    2006-01-01

    Inflammatory bowel disease is an important cause of gastrointestinal pathology in children and adolescents.The incidence of pediatric inflammatory bowel disease is increasing; therefore, it is important for the clinician to be aware of the presentation of this disease in the pediatric population. Laboratory tests, radiology studies,and endoscopic procedures are helpful in diagnosing inflammatory bowel disease and differentiating between Crohn's disease and ulcerative colitis. Once diagnosed,the goal of medical management is to induce remission of disease while minimizing the side effects of the medication. Specific attention needs to be paid to achieving normal growth in this susceptible population.Surgical management is usually indicated for failure of medical management, complication, or malignancy.Algorithms for diagnostic evaluation and treatment of pediatric inflammatory bowel disease are presented.The specific psychosocial issues facing these patients are also discussed in this review as are the future goals of research in the complex problem of pediatric inflammatory bowel disease.

  3. Short-Term Exercise Training Improves Insulin Sensitivity but Does Not Inhibit Inflammatory Pathways in Immune Cells from Insulin-Resistant Subjects

    Directory of Open Access Journals (Sweden)

    Sara M. Reyna

    2013-01-01

    Full Text Available Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD. Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC were obtained for determination of Toll-like receptor (TLR 2 and 4 protein content and mitogen-activated protein kinase phosphorylation. Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation. Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.

  4. Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of aortic atherosclerotic thrombi and ulcers.

    Science.gov (United States)

    Elsayed, Mahmoud; Bulur, Serkan; Kalla, Aditi; Ahmed, Mustafa I; Hsiung, Ming C; Uygur, Begum; Alagic, Nermina; Sungur, Aylin; Singh, Satinder; Nanda, Navin C

    2016-08-01

    We present two cases in whom live/real time three-dimensional transesophageal echocardiography (3DTEE) provided incremental value in the assessment of atherosclerotic disease in the aorta. In one patient, it identified additional atherosclerotic ulcers as well as thrombi within them which were missed by two-dimensional (2D) TEE. In both cases, the size of the large mobile atherosclerotic plaque was underestimated by 2DTEE as compared with 3DTEE. Furthermore, 3DTEE provided volume quantification of the thrombi and ulcers which is not possible by 2DTEE. The echocardiographic findings of atherosclerotic plaques were confirmed by computed tomography in one patient and by surgery in the other.

  5. [Inflammatory Bowel Disease Competence Network].

    Science.gov (United States)

    Schreiber, Stefan; Hartmann, Heinz; Kruis, Wolfgang; Kucharzik, Torsten; Mudter, Jonas; Siegmund, Britta; Stallmach, Andreas; Witte, Christine; Fitzke, Klaus; Bokemeyer, Bernd

    2016-04-01

    The Inflammatory Bowel Disease Competence Network is a network of more than 500 physicians and scientists from university clinics, hospitals and gastroenterology practices. The focus extends from the two major forms of inflammatory bowel diseases, Crohn's disease and ulcerative colitis, into other chronic inflammatory conditions affecting the intestine, including coeliac disease and microscopic colitis. The network translates basic science discoveries (in particular in the molecular epidemiology research) into innovative diagnostics and therapy. Through its strong networking structures it supports a continuous process to improve quality and standardisation in patient care that is implemented in close interaction with European networks addressing this disease group.Optimisation of patient care based on scientifically proven evidence is a main focus of the network. Therefore, it supports and coordinates translational research and infrastructure projects that investigate aetiology, improvement of diagnostic methods, and development of new or improved use of established therapies. Members participate in various training projects, thus ensuring the rapid transfer of research results into clinical practice.The competence network cooperates with the main patient organisations to engage patients in all levels of activities. The network and the patient organisations have interest in promoting public awareness about the disease entities, because their importance and burden is underestimated in non-specialised medical fields and among the general public.

  6. [Inflammatory Bowel Disease Competence Network].

    Science.gov (United States)

    Schreiber, Stefan; Hartmann, Heinz; Kruis, Wolfgang; Kucharzik, Torsten; Mudter, Jonas; Siegmund, Britta; Stallmach, Andreas; Witte, Christine; Fitzke, Klaus; Bokemeyer, Bernd

    2016-04-01

    The Inflammatory Bowel Disease Competence Network is a network of more than 500 physicians and scientists from university clinics, hospitals and gastroenterology practices. The focus extends from the two major forms of inflammatory bowel diseases, Crohn's disease and ulcerative colitis, into other chronic inflammatory conditions affecting the intestine, including coeliac disease and microscopic colitis. The network translates basic science discoveries (in particular in the molecular epidemiology research) into innovative diagnostics and therapy. Through its strong networking structures it supports a continuous process to improve quality and standardisation in patient care that is implemented in close interaction with European networks addressing this disease group.Optimisation of patient care based on scientifically proven evidence is a main focus of the network. Therefore, it supports and coordinates translational research and infrastructure projects that investigate aetiology, improvement of diagnostic methods, and development of new or improved use of established therapies. Members participate in various training projects, thus ensuring the rapid transfer of research results into clinical practice.The competence network cooperates with the main patient organisations to engage patients in all levels of activities. The network and the patient organisations have interest in promoting public awareness about the disease entities, because their importance and burden is underestimated in non-specialised medical fields and among the general public. PMID:26968556

  7. Arterial microcalcification in atherosclerotic patients with and without chronic kidney disease: a comparative high-resolution scanning X-ray diffraction analysis.

    Science.gov (United States)

    Fischer, Dagmar-Christiane; Behets, Geert J; Hakenberg, Oliver W; Voigt, Mathias; Vervaet, Benjamin A; Robijn, Stef; Kundt, Günther; Schareck, Wolfgang; D'Haese, Patrick C; Haffner, Dieter

    2012-06-01

    Vascular calcification, albeit heterogeneous in terms of biological and physicochemical properties, has been associated with ageing, lifestyle, diabetes, and chronic kidney disease (CKD). It is unknown whether or not moderately impaired renal function (CKD stages 2-4) affects the physiochemical composition and/or the formation of magnesium-containing tricalcium phosphate ([Ca,Mg](3)[PO(4)](2), whitlockite) in arterial microcalcification. Therefore, a high-resolution scanning X-ray diffraction analysis (European Synchrotron Radiation Facility, Grenoble, France) utilizing histological sections of paraffin-embedded arterial specimens derived from atherosclerotic patients with normal renal function (n = 15) and CKD (stages 2-4, n = 13) was performed. This approach allowed us to spatially assess the contribution of calcium phosphate (apatite) and whitlockite to arterial microcalcification. Per group, the number of samples (13 vs. 12) with sufficient signal intensity and total lengths of regions (201 vs. 232 μm) giving rise to diffractograms ("informative regions") were comparable. Summarizing all informative regions per group into one composite sample revealed calcium phosphate/apatite as the leading mineral phase in CKD patients, whereas in patients with normal renal function the relative contribution of whitlockite and calcium phosphate/apatite was on the same order of magnitude (CKD, calcium phosphate/apatite 157 μm, whitlockite 38.7 μm; non-CKD, calcium phosphate/apatite 79.0 μm, whitlockite 94.1 μm; each p < 0.05). Our results, although based on a limited number of samples, indicate that chronic impairment of renal function affects local magnesium homeostasis and thus contributes to the physicochemical composition of microcalcification in atherosclerotic patients.

  8. Inflammatory pseudotumor of kidney masquerading as renal carcinoma.

    Science.gov (United States)

    Babu, Prakash; Kalpana Kumari, M K; Nagaraj, H K; Mysorekar, Vijaya V

    2015-01-01

    Inflammatory pseudotumor also known as inflammatory fibroblastic tumor is a rare benign tumor, which commonly affects the lung. It is very rarely seen in the genitourinary tract. As the preoperative diagnosis, clinically and radiologically is inconclusive, it is imperative to surgically remove and confirm it on histopathologic examination. We report a case of inflammatory pseudotumor in a 51-year-old male who presented with flank pain and was treated with nephrectomy. PMID:26458713

  9. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

    Science.gov (United States)

    ... People About NINDS NINDS Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Information Page Table of Contents (click to jump ... en Español What is Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)? Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neurological ...

  10. 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.

  11. Predictors of atherosclerotic lesions of limb arteries according to cardioangiological screening of the adult population

    Directory of Open Access Journals (Sweden)

    R. A. Khokhlov

    2015-11-01

    Full Text Available Aim. To study the predictors of atherosclerotic lesions of arteries identified through a multi-channel volume sphygmography (MCVS. Material and methods. Simultaneous survey of 441 rural residents over 40 years old was performed. Synchronous registration of blood pressure (BP on four limbs using MCVS was fulfilled, and differences in systolic BP between arms (ΔSBParm and legs (ΔSBPleg were calculated. Ankle-brachial index (ABI was also evaluated. │ΔSBParm│≥15 mm Hg or │ΔSBPleg│≥15 mm Hg or ABI≤0.9 were considered as the markers of atherosclerotic arterial disease. Results. A significant asymmetry of SBP (≥15 mmHg was found in 7.7% [95% confidence interval (CI 5.5-10.6%] of patients in the upper limbs and in 6.8% (95 % CI 4.89.6% of patients in the lower extremities. The relative risk of asymmetry of SBP (≥15 mm Hg in the upper limbs increased in hypertension and obesity, and in the lower limbs in men and diabetes. Various quantitative risk factors of the onset and progression of atherosclerosis (age, body mass index, waist circumference, blood glucose, BP level had a positive correlation with the level of asymmetry of SBP on the limbs. Using MCVS and the appropriate combinations of features (SBP asymmetry or ABI≤0.9 allowed us at the stage of screening to find out blood flow disturbances in the arteries of the extremities in 14.7% (95% CI 11.7-18.4% of patients. This detection frequency was significantly higher than that when using only ABI. Conclusion. Identification of significant SBP asymmetry (≥15 mm Hg in the limbs may improve the diagnosis of atherosclerotic arterial disease at the stage of screening.

  12. Predictors of atherosclerotic lesions of limb arteries according to cardioangiological screening of the adult population

    Directory of Open Access Journals (Sweden)

    R. A. Khokhlov

    2015-01-01

    Full Text Available Aim. To study the predictors of atherosclerotic lesions of arteries identified through a multi-channel volume sphygmography (MCVS. Material and methods. Simultaneous survey of 441 rural residents over 40 years old was performed. Synchronous registration of blood pressure (BP on four limbs using MCVS was fulfilled, and differences in systolic BP between arms (ΔSBParm and legs (ΔSBPleg were calculated. Ankle-brachial index (ABI was also evaluated. │ΔSBParm│≥15 mm Hg or │ΔSBPleg│≥15 mm Hg or ABI≤0.9 were considered as the markers of atherosclerotic arterial disease. Results. A significant asymmetry of SBP (≥15 mmHg was found in 7.7% [95% confidence interval (CI 5.5-10.6%] of patients in the upper limbs and in 6.8% (95 % CI 4.89.6% of patients in the lower extremities. The relative risk of asymmetry of SBP (≥15 mm Hg in the upper limbs increased in hypertension and obesity, and in the lower limbs in men and diabetes. Various quantitative risk factors of the onset and progression of atherosclerosis (age, body mass index, waist circumference, blood glucose, BP level had a positive correlation with the level of asymmetry of SBP on the limbs. Using MCVS and the appropriate combinations of features (SBP asymmetry or ABI≤0.9 allowed us at the stage of screening to find out blood flow disturbances in the arteries of the extremities in 14.7% (95% CI 11.7-18.4% of patients. This detection frequency was significantly higher than that when using only ABI. Conclusion. Identification of significant SBP asymmetry (≥15 mm Hg in the limbs may improve the diagnosis of atherosclerotic arterial disease at the stage of screening.

  13. 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.

  14. Unfavorable Effects of Smoking on Atherosclerotic Risk Factors of Young Individuals

    Directory of Open Access Journals (Sweden)

    Zafer Isilak

    2009-06-01

    Full Text Available AIM: It was documented that smoking was a significant atherosclerotic risk factor for adults. However reality of the initiation of atherosclerosis at childhood guided us to evaluate the probable effects of smoking on other atherosclerotic risk factors at young ages. METHODS: One hundred sixty four young subjects (age 21.14± 2.06 were enrolled. Participants were grouped as not smoking (n=48, ex-smoking (n=30, 1-3 cigarettes/day (n=26, a half package/day (n=26, a package/day (n=34. Body mass index (BMI of subjects were calculated. Systolic and diastolic blood pressures (SBP, DBP were measured. Carotid intima media thickness (IMT was measured by Logic5 pro Colour Doppler Device. Total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels of subjects were measured from the serum obtained at 12 hour fasting state. IMT and IVSd were measured by transverse and 3S probes using. Statistical analysis was performed by One-way ANOVA test using SPSS 11.0 for Windows. RESULTS: BMI, SBP, and DBP were not different between groups (p=0.16. HDL cholesterol was significantly lowered whereas LDL cholesterol was significantly increased in group smoking one package/day. Also carotid IMT was increased in patients smoking one package/day compared to others but data was not statistically significant. Triglyceride level group. CONCLUSION: Smoking effects atherosclerotic risk factors unfavorably even at young ages. Thus smoking should be eradicated since earlier ages in order to reduce the prevalence of cardiovascular diseases. [TAF Prev Med Bull 2009; 8(3.000: 193-198

  15. Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin Ⅱ-stimulated macrophages

    Institute of Scientific and Technical Information of China (English)

    Chun LIANG; Zong-gui WU; Jian DING; Jian-fei JIANG; Gao-zhong HUANG; Rong-zeng DU; Jun-bo GE

    2004-01-01

    AIM: To explore whether the angiotensin Ⅱ (Ang Ⅱ) receptor 1 (AT1) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto induce experimental atheroma. Then either placebo or losartan 50 mg.kg-1.d-1 was administered in rats for another2 months. In vitro, the effect of losartan 0.1-10 μmol/L on the expression of MMP-2 and MMP-9 was investigated in Ang Ⅱ-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861±539 vs 8991±965, P<0.05; MMP-9,10527±1002 vs 14623±2462, P<0.01). In cultured rat peritoneal macrophages, Ang Ⅱ 0.1 μmol/L elicited an increase in MMP-2 and MMP-9 activity and expression that were prevented by losartan in a dose-dependent manner(P<0.01). But the AT2receptor antagonist PD123319 had no effect. CONCLUSION: Losartan reduced the expression and activity of MMP-2 and MMP-9 in rat atherosclerotic lesions. The anti-atherogenic effects of losartan were due to the direct inhibition of Ang Ⅱ bioactivity.

  16. Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin Ⅱ-stimulated macrophages

    Institute of Scientific and Technical Information of China (English)

    ChunLIANG; Zong-guiWU; JianDING; Jian-feiJIANG; Gao-zhongHUANG; Rong-zengDU; Jun-boGE

    2004-01-01

    AIM: To explore whether the angiotensin Ⅱ (Ang Ⅱ) receptor 1 (ATI) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip injected a single dose of vitamin D3 600 kU·kg·-1·month-1 and fed an atherogenic diet for 4 months to induce experimental atheroma. Then either placebo or losartan 50 kU·kg·-1·d-1 was administered in rats for another 2 months. In vitro, the effect of losartan 0.1-10 μmol/L on the expression of MMP-2 and MMP-9 was investigated in Ang Ⅱ-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861±539 vs 8991±965, P<0.05; MMP-9,10527±1002 vs 14623±2462, P<0.01). In cultured rat peritoneal macrophages, Ang Ⅱ 0.1 μmol/L elicited an increase in MMP-2 and MMP-9 activity and expression that were prevented by losartan in a dose-dependent manner (P<0.01). But the AT2receptor antagonist PD123319 had no effect. CONCLUSION: Losartan reduced the expression and activity of MMP-2 and MMP-9 in rat atherosclerotic lesions. The anti-atherogenic effects of losartan were due to the direct inhibition of Ang Ⅱ bioactivity.

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

    International Nuclear Information System (INIS)

    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 Cu2+-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

  18. Evaluation of the early enhancement of coronary atherosclerotic plaque by contrast-enhanced MR angiography

    International Nuclear Information System (INIS)

    Purpose: To evaluate the early enhancement of coronary atherosclerotic plaque using contrast-enhanced MR angiography (CE-MRA) and investigate the association between unstable angina pectoris (UAP) and early enhancement of the plaque. Methods: Forty-one patients presenting with angina pectoris and demonstrating single-vessel disease with non-calcified plaque and significant coronary stenosis (≥50%) on CTA were consecutively recruited for coronary CE-MRA. Contrast-to-noise ratio of the culprit plaque guided by CTA was measured on a cross-sectional multi-planar reconstruction image of the plaque on both pre- and post-CE-MRA. A 50% increasing of CNR was defined as plaque enhancement. The association between early enhancement of the plaques and UAP was analyzed. Results: Thirty-seven non-calcified plaques with significant coronary stenosis were detected in the 37 patients on MRA. 4 subjects were excluded because coronary atherosclerotic plaques were inadequate for identification on MRA. Of the 37 patients, 18 patients had UAP and other 19 patients presented stable angina pectoris (SAP). Of the 37 plaques on CE-MRA, 13 and 24 plaques presented early enhancement and no enhancement, respectively. Of the 13 early-enhanced plaques, 11 (85%) and 2 (15%) were found in the patients with UAP and SAP, respectively (p < 0.01). Of the 37 patients, 11 (61%) with UAP and 2 (11%) with SAP had early-enhanced plaques, respectively (p < 0.01). Conclusion: CE-MRA allows detection of early enhancement of coronary atherosclerotic plaque. The early enhancement is common in unstable angina and could be a sign of vulnerability.

  19. Ultrastructural characteristics of the vascular wall components of ruptured atherosclerotic abdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Tanasković Irena

    2013-01-01

    Full Text Available The aim of this study was to determine the ultrastructural characteristics of cell populations and extracellular matrix components in the wall of ruptured atherosclerotic abdominal aortic aneurysm (AAA. We analyzed 20 samples of ruptured AAA. For orientation to the light microscopy, we used routine histochemical techniques by standard procedures. For ultrastructural analysis, we applied transmission electron microscopy (TEM. Our results have shown that ruptured AAA is characterized by the remains of an advanced atherosclerotic lesion in the intima followed by a complete absence of endothelial cells, the disruption of basal membrane and disruption of internal elastic lamina. On plaque margins as well as in the inner media we observed smooth muscle cells (SMCs that posses a euchromatic nucleus, a well-developed granulated endoplasmic reticulum around the nucleus and reduced myofilaments. The remains of the ruptured lipid core were acellular in all samples; however, on the lateral sides of ruptured plaque we observed a presence of two types of foam cells (FCs, spindle- and star-shaped. Fusiform FCs possess a well-differentiated basal lamina, caveolae and electron dense bodies, followed by a small number of lipid droplets in the cytoplasm. Star-shaped FCs contain a large number of lipid droplets and do not possess basal lamina. On the inner margins of the plaque, we observed a large number of cells undergoing apoptosis and necrosis, extracellular lipid droplets as well as a large number of lymphocytes. The media was thinned out with disorganized elastic lamellas, while the adventitia exhibited leukocyte infiltration. The presented results suggest that atherosclerotic plaque in ruptured AAA contains vascular SMC synthetic phenotype and two different types of FCs: some were derived from monocyte/macrophage lineage, while others were derived from SMCs of synthetic phenotype. The striking plaque hypocellularity was the result of apoptosis and necrosis

  20. Estrogen suppression of I-125-cholesteryl ester uptake in atherosclerotic lesions in a rabbit model

    International Nuclear Information System (INIS)

    Cholesteryl esters (CE) are the principal lipids found in atherosclerotic lesions. A nonhydrolyzable CE analog, I-125-cholesteryl iopanoate (I-125-CI), that is rapidly associated with circulating lipoproteins was administered to New Zealand White rabbits rendered hypercholesterolemic to assess the effect of hypercholesterolemia and estrogen therapy upon the uptake of CI into developing atherosclerotic lesions. Atherosclerosis (A) was induced by aortic deendothelialization in 10 rabbits with a balloon embolectomy catheter introduced via the femoral artery, followed by a 2% cholesterol-enriched diet. Five of these 10 rabbits were treated with estradiol (AE) (0.5mg/Kg/week x 5); an additional 4 animals served as untreated, non-A controls. I-125-CI was administered intravenously in multiple doses over a 5 week interval. Gamma camera images and selected tissues were obtained 6 days after the completion of I-125-CI administration (total cumulative dose 82.6-87.3μCi/rabbit). Plasma cholesterol levels were 268 +- 162, 1940 +- 248 and 2484 +- 209 mg/dl in the untreated controls, A and AE groups, respectively. Atherosclerotic aortas were readily visualized in the A > AE groups as compared to untreated controls. Abdominal aortic tissues contained 0.013 +- 0.004, 0.187 +- 0.021, and 0.067 +- 0.015 %-Kg/dose/gm of I-125-CI from the untreated controls, A and AE groups, respectively. Thus, CI analogs can be used as probes to scintigraphically depict CE distribution and the effects of pharmacologic manipulation upon the accumulation of CE by vascular lesions in an animal model of atherosclerosis

  1. Evaluation of atherosclerotic change of the aorta by enhanced computed tomography

    International Nuclear Information System (INIS)

    Intimal atherosclerotic changes of the aorta were quantified by enhanced computed tomography (enhanced CT) and were examined in terms of their relation to other atherosclerotic characteristics, including calcification and aortic pulse wave velocity, diameter of the aorta, and arteriosclerotic risk factors. A total of 413 subjects were studied, consisting of normal volunteers and patients with cardiovascular diseases. Enhanced CT revealed the atheromatous intima as a projecting and thickened wall. Thus, the ratio of the intimal atherosclerotic change to the whole round was determined in various aortic sites. The diameter of the aorta decreased in accordance with the location from the ascending aorta to aortic ending. The diameter of the infrarenal abdominal aorta was 1.5 times larger than that of the ascending aorta, irrespective of age. The diameter of each region of the aorta increased with advancing age; in the age group of 70 years or older, it was 1.5 times larger that that in the age group of 40 years or younger. The intimal change was noted in the middle descending thoracic aorta and infrarenal abdominal aorta. It was proportional to an increase in the aortic pulse wave velocity, the diameter of the aorta, and the intimal calcification. Intimal changes of the aorta were increased in cerebrovascular disease, ischemic heart disease, arteriosclerosis obliterans, hypertension and diabetes mellitus. In particular, hypertension accompanied by diabetes mellitus or high cholesterolemia tended to accelerate the intimal change. In conclusion, aortic intimal changes, as detected on enhanced CT, is useful for the noninvasive diagnosis of arteriosclerosis. (N.K.)

  2. Evaluation of atherosclerotic change of the aorta by enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Takasu, Junichiro (Chiba Univ. (Japan). School of Medicine)

    1990-10-01

    Intimal atherosclerotic changes of the aorta were quantified by enhanced computed tomography (enhanced CT) and were examined in terms of their relation to other atherosclerotic characteristics, including calcification and aortic pulse wave velocity, diameter of the aorta, and arteriosclerotic risk factors. A total of 413 subjects were studied, consisting of normal volunteers and patients with cardiovascular diseases. Enhanced CT revealed the atheromatous intima as a projecting and thickened wall. Thus, the ratio of the intimal atherosclerotic change to the whole round was determined in various aortic sites. The diameter of the aorta decreased in accordance with the location from the ascending aorta to aortic ending. The diameter of the infrarenal abdominal aorta was 1.5 times larger than that of the ascending aorta, irrespective of age. The diameter of each region of the aorta increased with advancing age; in the age group of 70 years or older, it was 1.5 times larger that that in the age group of 40 years or younger. The intimal change was noted in the middle descending thoracic aorta and infrarenal abdominal aorta. It was proportional to an increase in the aortic pulse wave velocity, the diameter of the aorta, and the intimal calcification. Intimal changes of the aorta were increased in cerebrovascular disease, ischemic heart disease, arteriosclerosis obliterans, hypertension and diabetes mellitus. In particular, hypertension accompanied by diabetes mellitus or high cholesterolemia tended to accelerate the intimal change. In conclusion, aortic intimal changes, as detected on enhanced CT, is useful for the noninvasive diagnosis of arteriosclerosis. (N.K.).

  3. COMBINED INTRAOPERATIVE ILIAC ARTERY STENTS AND FEMORO-POPLITEAL BYPASS FOR MULTILEVEL ATHEROSCLEROTIC OCCLUSIVE DISEASE

    Institute of Scientific and Technical Information of China (English)

    刘昌伟; 管珩; 李拥军; 郑曰宏; 刘卫

    2001-01-01

    Objective. To review our preliminary experience and evaluate our early results of a combined intraoperative iliac angioplasty and stenting with infrainguinal revascularization in multilevel atherosclerotic occlusive disease.``Methods. From July 1999 to April 2000, intraoperative iliac angioplasty and stenting combined with simultaneous femoro-popliteal bypass were performed on 12 lower extremities of 10 patients suffering from multilevel atherosclerotic occlusive disease. There were 8 men and 2 women, average 72 years. The indications for procedures included disabling claudication in 3 and rest pain in 7 patients.``Results. Eleven iliac angioplasty and stent procedures combined with simultaneous 9 femoro-popliteal bypass and 3 femoro-femoral-popliteal bypass were performed in 12 limbs of 10 patients. Angioplasty and stent placement was technically successful in all patients. One contralateral femoral-popliteal bypass was failure after femorofemoral-popliteal bypass. There were no additional instances of procedural or postoperative morbidity or mortality. Mean follow-up was 5 months (range 1 ~ 10 months). During the follow-up period, one femoro-infrapoplitealgraft became occluded after 7 months and above-knee amputation was required. The cumulative primary patency rate of stented iliac arteries, femoro-femoral bypass grafts and femoro-popliteal bypass grafts were 100% ( 11 /11), 100% (3/3) and 90. 9% (10/11) in the follow-up period, respectively. The amputation rate was 8.3%(1/12).``Conclusions. Intraoperative iliac artery PTA and stent placement can be safely and effectively performed simultaneously with infrainguinal revascularization for multilevel atherosclerotic occlusive disease by skilled vascular surgeon, using a prtable C arm fluoroscopy in the operating room. Furthermore, iliac artery PTA and stenting was valuable adjunct to distal bypass either to improve inflow and outflow, or to reduce the extent of traditional surgical intervention, and also, any

  4. Management of inflammatory bowel disease in pregnancy

    NARCIS (Netherlands)

    S. Vermeire (Silvio); F. Carbonnel (Franck); P.G. Coulie (Pierre); V. Geenen (Vincent); J.M.W. Hazes (Mieke); P.L. Masson (Pierre); F. de Keyser (Filip); E. Louis (Edouard)

    2012-01-01

    textabstractBackground and Aims: Inflammatory bowel disease (IBD) is a chronic disease affecting mainly young people in their reproductive years. IBD therefore has a major impact on patients' family planning decisions. Management of IBD in pregnancy requires a challenging balance between optimal dis

  5. Current treatment for inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Chang-tai Xu; Xiue-gan Guo; Bo-rong Pan

    2003-01-01

    @@Introduction Idiopathic inflammatory bowel disease consists of Crohn's disease (CD) and ulcerative colitis (UC). CD can affect any part of the gastrointestinal tract, from the mouth to the anus, and is also known as regional enteritis, terminal ileitis, or granulomatous……

  6. Pelvic Inflammatory Disease

    Science.gov (United States)

    Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...

  7. Abolished synthesis of cholic acid reduces atherosclerotic development in apolipoprotein E knockout mice[S

    OpenAIRE

    Slätis, Katharina; Gåfvels, Mats; Kannisto, Kristina; Ovchinnikova, Olga; Paulsson-Berne, Gabrielle; Parini, Paolo; Jiang, Zhao-Yan; Eggertsen, Gösta

    2010-01-01

    To investigate the effects of abolished cholic acid (CA) synthesis in the ApoE knockout model [apolipoprotein E (apoE) KO],a double-knockout (DKO) mouse model was created by crossbreeding Cyp8b1 knockout mice (Cyp8b1 KO), unable to synthesize the primary bile acid CA, with apoE KO mice. After 5 months of cholesterol feeding, the development of atherosclerotic plaques in the proximal aorta was 50% less in the DKO mice compared with the apoE KO mice. This effect was associated with reduced inte...

  8. Factors Influencing the Disturbed Flow Patterns Downstream of Curved Atherosclerotic Arteries

    Institute of Scientific and Technical Information of China (English)

    Biyue Liu

    2008-01-01

    Pulsatile blood flows in curved atherosclerotic arteries are studied by com-puter simulations. Computations are carried out with various values of physiological parameters to examine the effects of flow parameters on the disturbed flow patterns downstream of a curved artery with a stenosis at the inner wall. The numerical re-sults indicate a strong dependence of flow pattern on the blood viscosity and inlet flow rate, while the influence of the inlet flow profile to the flow pattem in downstream is negligible.

  9. Snoring and atherosclerotic manifestations in a 70-year-old population

    DEFF Research Database (Denmark)

    Jennum, P; Schultz-Larsen, K; Christensen, N J

    1996-01-01

    the issue we examined the association between self-assessed snoring and the relation to atherosclerotic manifestations. 804 70-year-old males and females were classified according to snoring habits. Alcohol and tobacco consumption, blood pressure, body mass index, social group, plasma lipids (triglycerides......) into positive ECG signs (Q/OS waves, S-T depressions, T-wave inversion or flattering or left bundle branch block) and definitive myocardial infarction. Snoring showed a weak positive correlation to positive ECG signs and definitive myocardial infarction, but after adjustments for the above confounders...

  10. Feasibility of simultaneous PET/MR in diet-induced atherosclerotic minipig

    DEFF Research Database (Denmark)

    Pedersen, Sune F; Ludvigsen, Trine P; Johannesen, Helle H;

    2014-01-01

    glycolysis as given by standardized uptake values (SUV). Ex vivo en face evaluation of aortas from an atherosclerotic animal illustrated plaque distribution macroscopically, compared to a lean control animal. Although T2-TSE weighted imaging was most consistent, no one MRI sequence was preferable...... and superior to another for visualization and identification of the abdominal aorta. We found poor correlation between SUVs obtained from 10 and 20 minutes of reconstructed PET emission data. This can most likely be ascribed to intestinal movement. In conclusion multisequence MRI is recommended for optimal...

  11. Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques

    DEFF Research Database (Denmark)

    Woods, Alan A; Linton, Stuart M; Davies, Michael Jonathan

    2003-01-01

    Oxidation is believed to play a role in atherosclerosis. Oxidized lipids, sterols and proteins have been detected in early, intermediate and advanced human lesions at elevated levels. The spectrum of oxidized side-chain products detected on proteins from homogenates of advanced human lesions has...... material obtained from advanced human atherosclerotic lesions are shown to contain elevated levels of oxidized amino acids [3,4-dihydroxyphenylalanine (DOPA), di-tyrosine, 2-hydroxyphenylalanine ( o-Tyr)] when compared with healthy (human and pig) arterial tissue. These matrix-derived materials account...

  12. Prostacyclin: An inflammatory paradox.

    Directory of Open Access Journals (Sweden)

    Jeremiah eStitham

    2011-05-01

    Full Text Available Prostacyclin (PGI2 is a member of the prostaglandin family of bioactive lipids. Its best-characterized role is in the cardiovascular system, where it is released by vascular endothelial cells, serving as a potent vasodilator and inhibitor of platelet aggregation. In recent years, prostacyclin (PGI2 has also been shown to promote differentiation and inhibit proliferation in vascular smooth muscle cells. In addition to these well-described homeostatic roles within the cardiovascular system, prostacyclin (PGI2 also plays an important role as an inflammatory mediator. In this review, we focus on the contribution of prostacyclin (PGI2 as both a pathophysiological mediator and therapeutic agent in three major inflammatory-mediated disease processes, namely rheumatoid arthritis, where it promotes disease progression (pro-inflammatory, along with pulmonary vascular disease and atherosclerosis, where it inhibits disease progression (anti-inflammatory. The emerging role of prostacyclin (PGI2 in this context provides new opportunities for understanding the complex molecular basis for inflammatory-related diseases, and insights into the development of current and future anti-inflammatory treatments.

  13. The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

    Science.gov (United States)

    Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

    2013-11-01

    Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

  14. Association of Atherosclerotic Peripheral Arterial Disease with Adiponectin Genes SNP+45 and SNP+276: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Claudia D. Gherman

    2013-01-01

    Full Text Available Objectives. We hypothesized that adiponectin gene SNP+45 (rs2241766 and SNP+276 (rs1501299 would be associated with atherosclerotic peripheral arterial disease (PAD. Furthermore, the association between circulating adiponectin levels, fetuin-A, and tumoral necrosis factor-alpha (TNF-α in patients with atherosclerotic peripheral arterial disease was investigated. Method. Several blood parameters (such as adiponectin, fetuin-A, and TNF-α were measured in 346 patients, 226 with atherosclerotic peripheral arterial disease (PAD and 120 without symptomatic PAD (non-PAD. Two common SNPs of the ADIPOQ gene represented by +45T/G 2 and +276G/T were also investigated. Results. Adiponectin concentrations showed lower circulating levels in the PAD patients compared to non-PAD patients (P0.05. Conclusion. The results of our study demonstrated that neither adiponectin SNP+45 nor SNP+276 is associated with the risk of PAD.

  15. Addition of a novel, protective family history category allows better profiling of cardiovascular risk and atherosclerotic burden in the general population. The Asklepios Study.

    Directory of Open Access Journals (Sweden)

    Caroline M Van daele

    Full Text Available OBJECTIVES: Whereas the importance of family history (FH is widely recognized in cardiovascular risk assessment, its full potential could be underutilized, when applied with its current simple guidelines-based definition (cFH: presence of premature cardiovascular disease (CVD in a first-degree relative. We tested the added value of a new, extended family history definition (eFH, also taking into account later onset of disease, second-degree relatives and number of affected relatives, on profiling cardiovascular risk and atherosclerotic burden in the general population. DESIGN: Longitudinal population study. SETTING: Random, representative population sample from Erpe-Mere and Nieuwerkerken (Belgium, primary care. SUBJECTS: 2524 male/female volunteers, aged 35-55 years, free from overt CVD. MAIN OUTCOME MEASURES: Subjects were extensively phenotyped including presence of atherosclerosis (ultrasound and a newly developed FH questionnaire (4 generations. RESULTS: Compared to cFH, eFH was superior in predicting an adverse risk profile (glycemic state, elevated blood pressure, lipid abnormalities, presence of metabolic syndrome components and presence of atherosclerosis (all age & sex-adjusted p<0.05. Unlike cFH, eFH remained a significant predictor of subclinical atherosclerosis after adjusting for confounders. Most relations with eFH were not graded but showed clear informational breakpoints, with absence of CVD (including late onset in any first-degree relative being a negative predictor of atherosclerosis, and a particularly interesting phenotype for further study. CONCLUSIONS: A novel, extended FH definition is superior to the conventional definition in profiling cardiovascular risk and atherosclerotic burden in the general population. There remain clear opportunities to refine and increase the performance and informational content of this simple, readily-available inexpensive tool.

  16. Selective removal of cholesterol ester in atherosclerotic plaque using nanosecond pulsed laser at 5.75 μm

    Science.gov (United States)

    Ishii, K.; Tsukimoto, H.; Hazama, H.; Awazu, K.

    2008-02-01

    Laser angioplasty, for example XeCl excimer laser angioplasty, has gained more attention in addition to conventional methods of surgical and interventional treatment of atherosclerotic diseases such as bypass operation and balloon dilatation. Low degrees of thermal damage after ablation of atherosclerotic lesions have been achieved by XeCl excimer laser at 308 nm. However, in most cases, laser ablation is not selective and normal arterial wall is also damaged. To avoid complications such as severe dissections or perforation of the arterial wall in an angioplasty, a laser light source with high ablation efficiency but low arterial wall injury is desirable. At atherosclerotic lesions, cholesterol accumulates on the tunica intima by establishing an ester bond with fatty acids such as oleic acid, and thus cholesterol ester is the main component of atherosclerotic plaques. Mid-infrared pulsed laser at 5.75 μm is selectively well absorbed in C=O stretching vibration mode of ester bonds. The purpose of this study is to determine the effectiveness of nanosecond pulsed laser at 5.75 μm irradiation of cholesterol ester in atherosclerotic plaques. In this study, we used a mid-infrared tunable solid-state laser which is operated by difference frequency generation method, with a wavelength of 5.75 μm, a pulse width of 5 nsec and a pulse duration of 10 Hz. It was confirmed that non-invasive interaction to normal thoracic aortas could be induce by the parameters, the wavelength of 5.75 μm, the average power densities of 35 W/cm2 and the irradiation time under 10 sec. This study shows that nanosecond pulsed laser irradiations at 5.75 μm provide an alternative laser light source as an effectively cutting, less traumatic tool for removal of atherosclerotic plaque.

  17. Effect of Guanxinshutong capsule on the expression of matrix metalloproteinases-9 and tissue matrix metalloproteinase inhibitor-1 of atherosclerotic plaque in apoE-/- mice

    Institute of Scientific and Technical Information of China (English)

    霍煜

    2014-01-01

    Objective To approach the possible mechanism of Guanxinshutong capsule on the progression and stability of atherosclerotic plaque through observing the effects of Guanxinshutong capsule on pathologic morphology and expression of tissue matrix metalloproteinase inhibitor-1(TIMP-1),matrix metalloproteinases-9(MMP-9)of atherosclerotic plaque in Apo E-/-mice model with experimental atherosclerosis.Methods The animals were fed

  18. Effective risk stratification in patients with moderate cardiovascular risk using albuminuria and atherosclerotic plaques in the carotid arteries

    DEFF Research Database (Denmark)

    Greve, Sara V; Blicher, Marie K; Sehestedt, Thomas;

    2015-01-01

    /mmol in men/women. The composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for ischemic heart disease was recorded (n = 229). RESULTS: Both elevated UACR (P = 0.002) and atherosclerotic plaques (P ..., Systematic COronary Risk Evaluation (SCORE), and Framingham risk score (FRS) groups. Subclinical vascular damage was defined as carotid-femoral pulse wave velocity at least 12 m/s, and carotid atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 90th percentile of 0.73/1.06 mg...

  19. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice.

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    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

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

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    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

  1. Prognosis of non-significant coronary atherosclerotic disease detected by coronary artery tomography

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    Barros, Marcio Vinicius Lins; Siqueira, Bruna Pinto; Guimaraes, Carolina Camargos Braichi; Cruz, David Filipe Silva; Guimaraes, Leiziane Assuncao Alves; Lima, Maicom Marcio Perigolo, E-mail: marciovlbarros@gmail.com [Faculdade de Saude e Ecologia Humana, Vespasiano, MG (Brazil); Nunes, Maria do Carmo Pereira [Universidade de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina; Siqueira, Maria Helena Albernaz [Hospital Materdei, Belo Horizonte, MG (Brazil)

    2015-07-15

    Introduction: Although studies have shown high diagnostic accuracy of coronary tomography (CT) in detecting coronary artery disease (CAD), data on the prognostic value of this method in patients with no significant coronary obstruction are limited. Objective: To evaluate the value of CT in predicting adverse events in patients with suspected CAD and no significant coronary obstruction. Methods: We prospectively evaluated 440 patients between January 2008 and July 2013 by MDCT, diagnosed with no significant obstruction or no atherosclerotic coronary obstruction with an average follow-up of 33 months. The outcomes evaluated were: cardiac death, myocardial infarction, unstable angina associated with hospitalization or coronary artery bypass grafting. Results: Of the 440 patients studied, 295 (67%) were men with mean age 55.9 ± 12.0 years. Non-significant obstruction was found in 152 (35%) of the patients and there were 49 (11%) outcomes. In the multivariate analysis using the Cox regression model, the predictors of clinical outcomes were non-significant obstruction on CT (hazard ratio 3.51; 95% CI 1.73 - 7.8; p <0.01), age and hypertension. Non-significant obstruction on CT was associated with adverse clinical outcomes and survival analysis showed a significant difference (log-rank 24.6; p <0.01) in predicting these outcomes. Conclusion: The detection of non-significant atherosclerotic obstruction by CT was associated with the presence of adverse events in patients with suspected CAD, which may prove useful in the risk stratification of these patients. (author)

  2. Prognosis of non-significant coronary atherosclerotic disease detected by coronary artery tomography

    International Nuclear Information System (INIS)

    Introduction: Although studies have shown high diagnostic accuracy of coronary tomography (CT) in detecting coronary artery disease (CAD), data on the prognostic value of this method in patients with no significant coronary obstruction are limited. Objective: To evaluate the value of CT in predicting adverse events in patients with suspected CAD and no significant coronary obstruction. Methods: We prospectively evaluated 440 patients between January 2008 and July 2013 by MDCT, diagnosed with no significant obstruction or no atherosclerotic coronary obstruction with an average follow-up of 33 months. The outcomes evaluated were: cardiac death, myocardial infarction, unstable angina associated with hospitalization or coronary artery bypass grafting. Results: Of the 440 patients studied, 295 (67%) were men with mean age 55.9 ± 12.0 years. Non-significant obstruction was found in 152 (35%) of the patients and there were 49 (11%) outcomes. In the multivariate analysis using the Cox regression model, the predictors of clinical outcomes were non-significant obstruction on CT (hazard ratio 3.51; 95% CI 1.73 - 7.8; p <0.01), age and hypertension. Non-significant obstruction on CT was associated with adverse clinical outcomes and survival analysis showed a significant difference (log-rank 24.6; p <0.01) in predicting these outcomes. Conclusion: The detection of non-significant atherosclerotic obstruction by CT was associated with the presence of adverse events in patients with suspected CAD, which may prove useful in the risk stratification of these patients. (author)

  3. Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

    Science.gov (United States)

    Evani, Shankar J.; Ramasubramanian, Anand K.

    2016-01-01

    Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

    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. Baremetal stents and the subsequently developed drugeluting 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.

  5. Evaluation of radiotracers for the detection of atherosclerotic vulnerable plaque and myocardial angiogenesis

    International Nuclear Information System (INIS)

    Cardiovascular diseases are the leading cause of mortality worldwide. Coronary events are mainly caused by coronary plaque rupture or erosion. However, at present, there is no noninvasive tool available for the detection of vulnerable plaques. The first part of thesis is about evaluation of new radiotracers for the detection of atherosclerotic vulnerable plaques. 99mTc-B2702p, 20 derivatives, 99mTc-VP and 99mTc-VINP28 were evaluated in an experimental model of atherosclerosis (ApoE-/- mice with left carotid artery ligation). 99mTc- B2702p1 is a potentially useful radiotracer for the in vivo molecular imaging of VCAM-1 expression in atherosclerotic plaques. Myocardial angiogenesis is an important post infarction phenomenon. Angiogenic therapy improves experimentally cardiac parameters. However, clinical trials using the same therapy are more controversial. At present, clinical imaging tools don't allow us to assess angiogenesis therapy. The second part of thesis is about validation of 99mTc-RAFT-RGD in the detection of myocardial angiogenesis. 99mTc-RAFT-RGD allow us to perform noninvasive molecular imaging of myocardial angiogenesis in an experimental model. (author)

  6. Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries

    Science.gov (United States)

    McArdle, Sara; Chodaczek, Grzegorz; Ray, Nilanjan; Ley, Klaus

    2015-02-01

    Intravital multiphoton imaging of arteries is technically challenging because the artery expands with every heartbeat, causing severe motion artifacts. To study leukocyte activity in atherosclerosis, we developed the intravital live cell triggered imaging system (ILTIS). This system implements cardiac triggered acquisition as well as frame selection and image registration algorithms to produce stable movies of myeloid cell movement in atherosclerotic arteries in live mice. To minimize tissue damage, no mechanical stabilization is used and the artery is allowed to expand freely. ILTIS performs multicolor high frame-rate two-dimensional imaging and full-thickness three-dimensional imaging of beating arteries in live mice. The external carotid artery and its branches (superior thyroid and ascending pharyngeal arteries) were developed as a surgically accessible and reliable model of atherosclerosis. We use ILTIS to demonstrate Cx3cr1GFP monocytes patrolling the lumen of atherosclerotic arteries. Additionally, we developed a new reporter mouse (Apoe-/-Cx3cr1GFP/+Cd11cYFP) to image GFP+ and GFP+YFP+ macrophages "dancing on the spot" and YFP+ macrophages migrating within intimal plaque. ILTIS will be helpful to answer pertinent open questions in the field, including monocyte recruitment and transmigration, macrophage and dendritic cell activity, and motion of other immune cells.

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

    International Nuclear Information System (INIS)

    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 mm3, 90.4%) than in calcified plaque (median, 0.7 mm3, 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.

  8. Integrated analysis of microarray data of atherosclerotic plaques: modulation of the ubiquitin-proteasome system.

    Directory of Open Access Journals (Sweden)

    Zhe Wang

    Full Text Available Atherosclerosis is a typical complex multi-factorial disease and many molecules at different levels and pathways were involved in its development. Some studies have investigated the dysregulation in atherosclerosis at mRNA, miRNA or DNA methylation level, respectively. However, to our knowledge, the studies that integrated these data and revealed the abnormal networks of atherosclerosis have not been reported. Using microarray technology, we analyzed the omics data in atherosclerosis at mRNA, miRNA and DNA methylation levels. Our results demonstrated that the global DNA methylation and expression of miRNA/mRNA were significantly decreased in atherosclerotic plaque than in normal vascular tissue. The interaction network constructed using the integrative data revealed many genes, cellular processes and signaling pathways which were widely considered to play crucial roles in atherosclerosis and also revealed some genes, miRNAs or signaling pathways which have not been investigated in atherosclerosis until now (e.g. miR-519d and SNTB2. Moreover, the overall protein ubiquitination in atherosclerotic plaque was significantly increased. The proteasome activity was increased early but decreased in advanced atherosclerosis. Our study revealed many classic and novel genes and miRNAs involved in atherosclerosis and indicated the effects of ubiquitin-proteasome system on atherosclerosis might be closely related to the course of atherosclerosis. However, the efficacy of proteasome inhibitors in the treatment of atherosclerosis still needs more research.

  9. Evaluation of early atherosclerotic findings in women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Mohammadi Afshin

    2011-10-01

    Full Text Available Background Polycystic ovary syndrome (PCOS is the most common endocrinopathy in women of childbearing age, and it seems better to consider it as an ovarian manifestation of metabolic syndrome. The aim of the current study was to evaluate early atherosclerotic findings in patients with PCOS. Methods We enrolled 46 women with PCOS and 45 normal control subjects who were referred to our hospital's endocrinology outpatient clinic. Carotid intima media thickness (CIMT and flow-mediated dilatation (FMD were performed in both cases and matched controls. Results Patients with PCOS showed an increased mean CIMT (0.63 ± 0.16 mm when compared with the control subjects (0.33 ± 0.06 mm. This difference was statistically significant (p = 0.001. The mean FMD in young patients with PCOS was 10.07 ± 1.2%, while it was 6.5 ± 2.06% in normal subjects. This difference was also statistically significant (p = 0.001. Conclusion Our findings suggest that PCOS is related with early atherosclerotic findings.

  10. 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.

  11. Real-Time Elastography Visualization and Histopathological Characterization of Rabbit Atherosclerotic Carotid Arteries.

    Science.gov (United States)

    Wang, ZhenZhen; Liu, NaNa; Zhang, LiFeng; Li, XiaoYing; Han, XueSong; Peng, YanQing; Dang, MeiZheng; Sun, LiTao; Tian, JiaWei

    2016-01-01

    To evaluate the feasibility of non-invasive vascular real-time elastography imaging (RTE) in visualizing the composition of rabbit carotid atherosclerotic plaque as determined by histopathology, a rabbit model of accelerated carotid atherosclerosis was used. Thirty rabbits were randomly divided into two groups of 15 rabbits each. The first group was fed a cholesterol-rich diet and received balloon-induced injury the left common carotid artery endothelium, whereas the second group only received a cholesterol-rich diet. The rabbits were all examined in vivo with HITACHI non-invasive vascular real-time elastography (Hi-RTE) at baseline and 12 wk, and results from the elastography were compared with American Heart Association histologic classifications. Hi-RTE and the American Heart Association histologic classifications had good agreement, with weighted Cohen's kappa (95% confidence internal) of 0.785 (0.649-0.920). Strains of segmented plaques that were stained in different colors were statistically different (p visualizing normal and atherosclerotic rabbit carotid arteries non-invasively. This affordable and reliable method can be widely applied in research of both animal and human peripheral artery atherosclerosis.

  12. Oleic acid induces smooth muscle foam cell formation and enhances atherosclerotic lesion development via CD36

    Directory of Open Access Journals (Sweden)

    Tang Bing

    2011-04-01

    Full Text Available Abstract Background Elevated plasma free fatty acid (FFA levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36 is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36. Results We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs treated with oleic acid (OA. We found that OA induces lipid accumulation in SMCs in a dose dependent manner. Rat aortic SMCs treated for 48 hours with OA (250 μmol/L became foam cells based on morphological (Oil Red O staining and biochemical (5 times increase in cellular triglyceride criteria. Moreover, specific inhibition of CD36 by sulfo-N-succinimidyl oleate significantly attenuated OA induced lipid accumulation and foam cell formation. To confirm these results in vivo, we used ApoE-deficient mice fed with normal chow (NC, OA diet, NC plus lipolysis inhibitor acipimox or OA plus acipimox. OA-fed mice showed increased plasma FFA levels and enhanced atherosclerotic lesions in the aortic sinus compared to the NC group (both p 5 μm2 vs. OA plus acipimox: 2.60 ± 0.10 ×105 μm2, p p Conclusions These findings suggest that OA induces smooth muscle foam cell formation and enhances atherosclerotic lesions in part though CD36. Furthermore, these findings provide a novel model for the investigation of atherosclerosis.

  13. Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits

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    Raj Santhana

    2010-04-01

    Full Text Available Abstract Background Piper sarmentosum (P.s has flavonoid component in its leaves which has antioxidative effect. To date, its effect on atherosclerosis has not been studied histologically. Aim The study aimed to investigate the effect of P.s on atherosclerotic changes in hypercholesterolemic rabbits. Methods Forty two male New Zealand white rabbits were divided into seven groups. C - control group fed normal rabbit chow, CH - cholesterol diet (1% cholesterol, W1 - 1% cholesterol with water extract of P.s (62.5 mg/kg, W2 - 1% cholesterol with water extract of P.s (125 mg/kg, W3 - 1% cholesterol with water extract of P.s (250 mg/kg, W4 - 1% cholesterol with water extract of P.s (500 mg/kg and Smv - 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg. All rabbits were treated for 10 weeks. Following 10 weeks of supplementation, the animals were sacrificed and the aortic tissue was taken for histological study. Results Rabbits fed only with high cholesterol diet 1% cholesterol (CH showed focal fatty streak lesions compared to the C group and 1% cholesterol supplemented with simvistatin drug (Smv group. Atherosclerotic lesions in the 1% cholesterol group supplemented with P.s (500 mg/kg i.e. W4 group showed significant reduction (30 ± 6.0%, p Conclusion Administration of P.s extract has protective effect against atheroscleros

  14. A novel compound C12 inhibits inflammatory cytokine production and protects from inflammatory injury in vivo.

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    Yi Wang

    Full Text Available Inflammation is a hallmark of many diseases. Although steroids and cyclooxygenase inhibitors are main anti-inflammatory therapeutical agents, they may cause serious side effects. Therefore, developing non-steroid anti-inflammatory agents is urgently needed. A novel hydrosoluble compound, C12 (2,6-bis(4-(3-(dimethylamino-propoxybenzylidenecyclohexanone, has been designed and synthesized as an anti-inflammatory agent in our previous study. In the present study, we investigated whether C12 can affect inflammatory processes in vitro and in vivo. In mouse primary peritoneal macrophages, C12 potently inhibited the production of the proinflammatory gene expression including TNF-α, IL-1β, IL-6, iNOS, COX-2 and PGE synthase. The activity of C12 was partly dependent on inhibition of ERK/JNK (but p38 phosphorylation and NF-κB activation. In vivo, C12 suppressed proinflammatory cytokine production in plasma and liver, attenuated lung histopathology, and significantly reduced mortality in endotoxemic mice. In addition, the pre-treatment with C12 reduced the inflammatory pain in the acetic acid and formalin models and reduced the carrageenan-induced paw oedema and acetic acid-increased vascular permeability. Taken together, C12 has multiple anti-inflammatory effects. These findings, coupled with the low toxicity and hydrosolubility of C12, suggests that this agent may be useful in the treatment of inflammatory diseases.

  15. Inflammatory reaction in chondroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Yamamura, Sigeki [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Sato, Keiji [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Sugiura, Hideshi [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Iwata, Hisashi [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan)

    1996-05-01

    The objective of this study was to evaluate the inflammatory reaction accompanying chondroblastoma and to define the value of the finding in clinical practice. We reviewed the clinical, radiographic, and magnetic resonance (MR) findings in six patients with histologically proven chondroblastoma. In all cases, MR imaging showered marrow and soft tissue edema. In four of six cases, periosteal reaction related to intra-osseous edema was more clearly demonstrated on MR imaging than on radiographs. Follow-up MR studies after surgery were available in three patients and all showed disappearance of inflammatory responses such as marrow and soft tissue edema, and reactive synovitis. We propose that these inflammatory reactions of chondroblastomas are inportant signs for detecting residual tumor in recurrences after surgery, as well as for making a precise diagnosis. The MR changes may also be valuable in demonstrating eradication of the tumor. (orig./MG)

  16. Extraintestinal manifestations and complications in inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Katja S Rothfuss; Eduard F Stange; Klaus R Herrlinger

    2006-01-01

    Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that often involve organs other than those of the gastrointestinal tract. These nonintestinal affections are termed extraintestinal symptoms. Differentiating the true extraintestinal manifestations of inflammatory bowel diseases from secondary extraintestinal complications, caused by malnutrition, chronic inflammation or side effects of therapy, may be difficult. This review concentrates on frequency, clinical presentation and therapeutic implications of extraintestinal symptoms in inflammatory bowel diseases. If possible, extraintestinal manifestations are differentiated from extraintestinal complications. Special attention is given to the more recently described sites of involvement; I.e. Thromboembolic events, osteoporosis, pulmonary involvement and affection of the central nervous system.

  17. Inhibition of inflammatory arthritis using fullerene nanomaterials.

    Directory of Open Access Journals (Sweden)

    Anthony L Dellinger

    Full Text Available Inflammatory arthritis (e.g. rheumatoid arthritis; RA is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC. Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked FcγR- and TNF-α-induced mediator release from MC; TNF-α-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and FcγR-mediated increases in cellular reactive oxygen species and NF-κB activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-α. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis.

  18. Inflammatory Macrophages Promotes Development of Diabetic Encephalopathy

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    Beiyun Wang

    2015-06-01

    Full Text Available Background/Aims: Diabetes and Alzheimer's disease are often associated with each other, whereas the relationship between two diseases is ill-defined. Although hyperglycemia during diabetes is a major cause of encephalopathy, diabetes may also cause chronic inflammatory complications including peripheral neuropathy. Hence the role and the characteristics of inflammatory macrophages in the development of diabetic encephalopathy need to be clarified. Methods: Diabetes were induced in mice by i.p. injection of streptozotocin (STZ. Two weeks after STZ injection and confirmation of development of diabetes, inflammatory macrophages were eliminated by i.p. injection of 20µg saporin-conjugated antibody against a macrophage surface marker CD11b (saporin-CD11b twice per week, while a STZ-treated group received injection of rat IgG of same frequency as a control. The effects of macrophage depletion on brain degradation markers, brain malondialdehyde (MDA, catalase, superoxidase anion-positive cells and nitric oxide (NO were measured. Results: Saporin-CD11b significantly reduced inflammatory macrophages in brain, without affecting mouse blood glucose, serum insulin, glucose responses and beta cell mass. However, reduced brain macrophages significantly inhibited the STZ-induced decreases in brain MDA, catalase and superoxidase anion-positive cells, and the STZ-induced decreases in brain NO. Conclusion: Inflammatory macrophages may promote development of diabetic encephalopathy.

  19. Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

    NARCIS (Netherlands)

    Jager, Nynke A.; de Vries, Bastiaan M. Wallis; Hillebrands, Jan-Luuk; Harlaar, Niels J.; Tio, Rene A.; Slart, Riemer H. J. A.; van Dam, Gooitzen M.; Boersma, Hendrikus H.; Zeebregts, Clark J.; Westra, Johanna

    2016-01-01

    In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated. Twenty-three consecutive plaques removed during carotid endarter

  20. Selective removal of atherosclerotic plaque with a quantum cascade laser in the 5.7 µm wavelength range

    International Nuclear Information System (INIS)

    Atherosclerotic plaques consist mainly of cholesteryl esters, and the C=O stretching vibration mode of cholesteryl esters strongly absorbs radiation at a wavelength of 5.75 µm. For clinical application of less-invasive laser angioplasty with 5.75 µm, a compact laser is required. Quantum cascade lasers (QCLs) are semiconductor lasers that can emit radiation in the mid-IR range. In this study, the potential of the QCL for less-invasive laser angioplasty was evaluated. At the average power density of 180 W/cm2, the atherosclerotic aorta was ablated for the irradiation time of 1 s or more, whereas the normal aorta was ablated for more than 10 s. This demonstrates that selective ablation of the atherosclerotic aorta was achieved. However, strong coagulation and carbonization were observed. For reducing thermal effects, improving the pulse structure is required. In conclusion, the QCL achieved the selective ablation of the atherosclerotic lesions, which indicates the potential of the QCL. (author)

  1. IgM antibody level against proinflammatory bacterial peptidoglycan is inversely correlated with extent of atherosclerotic disease

    NARCIS (Netherlands)

    M.M.O. Nijhuis; Y. van der Graaf (Yolanda); M.J. Melief; A.H. Schoneveld (Arjan); D.P.V. de Kleijn (Dominique); J.D. Laman (Jon); G. Pasterkamp (Gerard)

    2004-01-01

    textabstractObjective: Atherosclerosis may lead to acute clinical events by rupture of a vulnerable atherosclerotic plaque. Previously, we demonstrated that peptidoglycan (PGN), a major cell wall component of gram-positive bacteria that induces production of proinflammatory cytokines through TLR2 an

  2. Circulating Leukocyte and Carotid Atherosclerotic Plaque Telomere Length Interrelation, Association With Plaque Characteristics, and Restenosis After Endarterectomy

    NARCIS (Netherlands)

    Huzen, Jardi; Peeters, Wouter; de Boer, Rudolf A.; Moll, Frans L.; Wong, Liza S. M.; Codd, Veryan; de Kleijn, Dominique P. V.; de Smet, Bart J. G. L.; van Veldhuisen, Dirk J.; Samani, Nilesh J.; van Gilst, Wiek H.; Pasterkamp, Gerard; van der Harst, Pim

    2011-01-01

    Objective-Shorter leukocyte telomeres are associated with atherosclerosis and predict future heart disease. The goal of the present study was to determine whether leukocyte telomere length is related to atherosclerotic plaque telomere length and whether it is associated with plaque characteristics o

  3. Comparison of osteoprotegerin to traditional atherosclerotic risk factors and high-sensitivity C-reactive protein for diagnosis of atherosclerosis

    DEFF Research Database (Denmark)

    Mogelvang, Rasmus; Pedersen, Sune H; Flyvbjerg, Allan;

    2012-01-01

    (OPG) to clinical and subclinical atherosclerotic disease in a large community-based, cross-sectional population study. In the Copenhagen City Heart Study, OPG concentrations were measured in 5,863 men and women. A total of 494 participants had been hospitalized for ischemic heart disease or ischemic...

  4. Digital Image Analysis of Ultrasound B-mode images of Carotid Atherosclerotic Plaque: Correlation with Histological Examination

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Rosendal, Kim; Grønholdt, Marie-Louise Moes;

    1996-01-01

    This paper reports on a study of how well texture features extracted from B-mode images of atherosclerotic plaque correlates with histological results obtained from the same plaque after carotid endarterectomy. The study reveals that a few second order texture features (diagonal moment, standard...

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

    Science.gov (United States)

    Myasoedova, Veronika A.; Kirichenko, Tatyana V.; Melnichenko, Alexandra A.; Orekhova, Varvara A.; Ravani, Alessio; Poggio, Paolo; Sobenin, Igor A.; Bobryshev, Yuri V.; Orekhov, Alexander N.

    2016-01-01

    The risk of cardiovascular disease and atherosclerosis progression is significantly increased after menopause, probably due to the decrease of estrogen levels. The use of hormone replacement therapy (HRT) for prevention of cardiovascular disease in older postmenopausal failed to meet expectations. Phytoestrogens may induce some improvements in climacteric symptoms, but their effect on the progression of atherosclerosis remains unclear. The reduction of cholesterol accumulation at the cellular level should lead to inhibition of the atherosclerotic process in the arterial wall. The inhibition of intracellular lipid deposition with isoflavonoids was suggested as the effective way for the prevention of plaque formation in the arterial wall. The aim of this double-blind, placebo-controlled clinical study was to investigate the effect of an isoflavonoid-rich herbal preparation on atherosclerosis progression in postmenopausal women free of overt cardiovascular disease. One hundred fifty-seven healthy postmenopausal women (age 65 ± 6) were randomized to a 500 mg isoflavonoid-rich herbal preparation containing tannins from grape seeds, green tea leaves, hop cone powder, and garlic powder, or placebo. Conventional cardiovascular risk factors and intima-media thickness of common carotid arteries (cIMT) were evaluated at the baseline and after 12 months of treatment. After 12-months follow-up, total cholesterol decreased by 6.3% in isoflavonoid-rich herbal preparation recipients (p = 0.011) and by 5.2% in placebo recipients (p = 0.020); low density lipoprotein (LDL) cholesterol decreased by 7.6% in isoflavonoid-rich herbal preparation recipients (p = 0.040) and by 5.2% in placebo recipients (non-significant, NS); high density lipoprotein (HDL) cholesterol decreased by 3.4% in isoflavonoid-rich herbal preparation recipients (NS) and by 4.5% in placebo recipients (p = 0.038); triglycerides decreased by 6.0% in isoflavonoid-rich herbal preparation recipients (NS) and by 7.1% in

  6. 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.

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

    Science.gov (United States)

    Myasoedova, Veronika A; Kirichenko, Tatyana V; Melnichenko, Alexandra A; Orekhova, Varvara A; Ravani, Alessio; Poggio, Paolo; Sobenin, Igor A; Bobryshev, Yuri V; Orekhov, Alexander N

    2016-01-01

    The risk of cardiovascular disease and atherosclerosis progression is significantly increased after menopause, probably due to the decrease of estrogen levels. The use of hormone replacement therapy (HRT) for prevention of cardiovascular disease in older postmenopausal failed to meet expectations. Phytoestrogens may induce some improvements in climacteric symptoms, but their effect on the progression of atherosclerosis remains unclear. The reduction of cholesterol accumulation at the cellular level should lead to inhibition of the atherosclerotic process in the arterial wall. The inhibition of intracellular lipid deposition with isoflavonoids was suggested as the effective way for the prevention of plaque formation in the arterial wall. The aim of this double-blind, placebo-controlled clinical study was to investigate the effect of an isoflavonoid-rich herbal preparation on atherosclerosis progression in postmenopausal women free of overt cardiovascular disease. One hundred fifty-seven healthy postmenopausal women (age 65 ± 6) were randomized to a 500 mg isoflavonoid-rich herbal preparation containing tannins from grape seeds, green tea leaves, hop cone powder, and garlic powder, or placebo. Conventional cardiovascular risk factors and intima-media thickness of common carotid arteries (cIMT) were evaluated at the baseline and after 12 months of treatment. After 12-months follow-up, total cholesterol decreased by 6.3% in isoflavonoid-rich herbal preparation recipients (p = 0.011) and by 5.2% in placebo recipients (p = 0.020); low density lipoprotein (LDL) cholesterol decreased by 7.6% in isoflavonoid-rich herbal preparation recipients (p = 0.040) and by 5.2% in placebo recipients (non-significant, NS); high density lipoprotein (HDL) cholesterol decreased by 3.4% in isoflavonoid-rich herbal preparation recipients (NS) and by 4.5% in placebo recipients (p = 0.038); triglycerides decreased by 6.0% in isoflavonoid-rich herbal preparation recipients (NS) and by 7.1% in

  8. Secretion of One Adipokine Nampt/Visfatin Suppresses the Inflammatory Stress-Induced NF-κB Activity and Affects Nampt-Dependent Cell Viability in Huh-7 Cells

    Directory of Open Access Journals (Sweden)

    Yi-Ching Lin

    2015-01-01

    Full Text Available Nampt/visfatin acts in both intracellular and extracellular compartments to regulate multiple biological roles, including NAD metabolism, cancer, inflammation, and senescence. However, its function in chronic inflammation and carcinogenesis in hepatocellular carcinoma (HCC has not been well-defined. Here we use Huh-7 hepatoma cells as a model to determine how Nampt/visfatin affects cellular survival under oxidative stress. We found that the transition of Nampt/visfatin from intracellular into extracellular form was induced by H2O2 treatment in 293T cells and confirmed that this phenomenon was not due to cell death but through the secretion of Nampt/visfatin. In addition, Nampt/visfatin suppressed cell viability in oxidative treatment in Huh-7 cells and acted on the inhibition of hepatoma cell growth. Oxidative stress also reduced the Nampt-mediated activation of NF-κB gene expression. In this study, we identify a novel feature of Nampt/visfatin which functions as an adipokine that can be secreted upon cellular stress. Our results provide an example to understand how adipokine interacts with chemotherapeutic treatment by oxidative stress in HCC.

  9. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P;

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  10. Inflammatory bowel disease epidemiology

    DEFF Research Database (Denmark)

    Burisch, Johan; Munkholm, Pia

    2013-01-01

    The occurrence of inflammatory bowel disease (IBD) is increasing worldwide, yet the reasons remain unknown. New therapeutic approaches have been introduced in medical IBD therapy, but their impact on the natural history of IBD remains uncertain. This review will summarize the recent findings...... in the epidemiology of IBD....

  11. Inflammatory mediators in osteoarthritis

    NARCIS (Netherlands)

    Beekhuizen, M.

    2014-01-01

    Osteoarthritis (OA) is a degenerative joint disorder involving cartilage destruction and joint inflammation. Despite extensive research, still much is unknown on the pathogenesis and aetiology of OA. Inflammation and inflammatory mediators (both local and systemic) are key in the pathogenesis of OA.

  12. Inflammatory Breast Cancer

    Science.gov (United States)

    ... breast cancer: consensus statement for standardized diagnosis and treatment. Annals of Oncology 2011; 22(3):515-523. [PubMed Abstract] Fouad TM, Kogawa T, Reuben JM, Ueno NT. The role of inflammation in inflammatory breast cancer. Advances in Experimental Medicine and Biology 2014; 816:53-73. [PubMed ...

  13. Metallothionein as an Anti-Inflammatory Mediator

    Directory of Open Access Journals (Sweden)

    Ken-ichiro Inoue

    2009-01-01

    Full Text Available The integration of knowledge concerning the regulation of MT, a highly conserved, low molecular weight, cystein-rich metalloprotein, on its proposed functions is necessary to clarify how MT affects cellular processes. MT expression is induced/enhanced in various tissues by a number of physiological mediators. The cellular accumulation of MT depends on the availability of cellular zinc derived from the diet. MT modulates the binding and exchange/transport of heavy metals such as zinc, cadmium, or copper under physiological conditions and cytoprotection from their toxicities, and the release of gaseous mediators such as hydroxyl radicals or nitric oxide. In addition, MT reportedly affects a number of cellular processes, such as gene expression, apoptosis, proliferation, and differentiation. Given the genetic approach, the apparently healthy status of MT-deficient mice argues against an essential biological role for MT; however, this molecule may be critical in cells/tissues/organs in times of stress, since MT expression is also evoked/enhanced by various stresses. In particular, because metallothionein (MT is induced by inflammatory stress, its roles in inflammation are implied. Also, MT expression in various organs/tissues can be enhanced by inflammatory stimuli, implicating in inflammatory diseases. In this paper, we review the role of MT of various inflammatory conditions.

  14. Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms

    OpenAIRE

    Owen P. Smith; Nasir Mahmud; Weir, Donald G.; Lesley Mynett-Johnson; Judith Conroy; Livingstone, Wendy J; Joanna Balding

    2004-01-01

    The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding va...

  15. 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

    , there was a positive association between the expression of EL mRNA and CD68 mRNA in plaques from 26 patients. The impact of differentiation from monocytes into macrophages, and subsequently foam cells (by incubation with acetylated LDL) on expression was studied using THP-1 monocytes and primary human monocytes. EL m...... 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......RNA expression increased markedly when either type of monocytes was differentiated into macrophages. Upon further differentiation into foam cells EL mRNA decreased whereas protein levels remained high compared to monocytes. In conclusion, macrophages in advanced human atherosclerotic lesions display high levels...

  16. 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...... compound ultrasound (US) and subsequently sliced and photographed to produce a 3D anatomical data set. Outlines in the ultrasound data were found by means of active contours and combined into 10 3D ultrasound models. The plaque regions of the anatomical photographs were outlined manually and then combined...... into 10 3D anatomical models. The volumes of the anatomical models correlated with the volume found by a water displacement method (r = 0.95), except for an offset. The models were compared in three ways. Visual inspection showed quite good agreement between the models. The volumes of the ultrasound...

  17. Atherosclerotic risk factors are increased in clinically healthy subjects with microalbuminuria

    DEFF Research Database (Denmark)

    Jensen, J S; Borch-Johnsen, K; Jensen, G;

    1995-01-01

    Increased morbidity and mortality from atherosclerotic vascular disease were observed in subjects with slightly elevated urinary albumin excretion rate (UAER), known as microalbuminuria. Therefore, the association between microalbuminuria and established atherogenic risk factors was studied...... and fasting serum insulin concentration were slightly elevated in the microalbuminuric group but not statistically significant. It is concluded that microalbuminuria in clinically healthy subjects is associated with increased levels of atherogenic risk factors. This may contribute to the increased vascular...... in clinically healthy subjects. All healthy 40-65 year-old participants with microalbuminuria, examined within the first 21 months of The Copenhagen City Heart Study, were invited, and 28 were studied. An age- and sex-matched group of 60 randomly chosen subjects with normoalbuminuria served as control...

  18. 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

    RNA expression increased markedly when either type of monocytes was differentiated into macrophages. Upon further differentiation into foam cells EL mRNA decreased whereas protein levels remained high compared to monocytes. In conclusion, macrophages in advanced human atherosclerotic lesions display high levels......, there was a positive association between the expression of EL mRNA and CD68 mRNA in plaques from 26 patients. The impact of differentiation from monocytes into macrophages, and subsequently foam cells (by incubation with acetylated LDL) on expression was studied using THP-1 monocytes and primary human monocytes. EL m...... of EL expression, and the level of EL expression varies greatly during transformation of blood monocytes into foam cells....

  19. Study of apolipoprotein E genetic polymorphism in patients with atherosclerotic cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    罗本燕; 陈智; 陈峰; 李霞; 潘小平

    2003-01-01

    Objective : To explore the frequency and significance of ApoE gene polymorphisms in Chinese patiems with atherosclerotic cerebral infarction (ACI). Methods: Polymerase chain reaction and gene sequencing, single nucleotide polymorphisms of ApoE gene were used to analyze 33 cases of patients with ACI and 35 controls. Results: The frequencies of ApoE gene single nucleotide polymorphisms 465C/G, 462C/G and 451delC in the ACI group were significantly higher than those in the control group (P <0.05) . The preva-lence of polymorphism 486G/T in the control group was significantly higher than that in the ACI group ( P =0.011 ). Conclusions : 465 C/G, 462C/G and 451 delC polymorphisms might be associated with ACI. 486GT allele might have protective effect on the pathogenesis of ACI.

  20. Study of apolipoprotein E genetic polymorphism in patients with atherosclerotic cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    罗本燕; 陈智; 陈峰; 李霞; 潘小平

    2003-01-01

    Objective: To explore the frequency and significance of ApoE gene polymorphisms in Chinese patients with atherosclerotic cerebral infarction (ACI). Methods: Polymerase chain reaction and gene sequencing, single nucleotide polymorphisms of ApoE gene were used to analyze 33 cases of patients with ACI and 35 controls. Results: The frequencies of ApoE gene single nucleotide polymorphisms 465C/G, 462C/G and 451delC in the ACI group were significantly higher than those in the control group (P<0.05). The prevalence of polymorphism 486G/T in the control group was significantly higher than that in the ACI group (P=0.011). Conclusions: 465C/G,462C/G and 451delC polymorphisms might be associated with ACI.486GT allele might have protective effect on the pathogenesis of ACI.

  1. Gene expression of LOX-1, VCAM-1, and ICAM-1 in pre-atherosclerotic mice

    DEFF Research Database (Denmark)

    Fisker Hag, Anne Mette; Pedersen, Sune Folke; Kjaer, Andreas

    2008-01-01

    To identify markers of the earliest stage of atherosclerosis, endothelial dysfunction, we evaluated the gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in very young pre......-atherosclerotic mice. Furthermore, the plasma levels of the soluble VCAM-1 and ICAM-1 were compared to the gene expression profiles. Gene expressions of LOX-1 and VCAM-1 were up-regulated in young apoE(-/-) mice, and thus, it seems probable that these genes play a role in pre-atherosclerosis. Contrarily, the gene...... expression profile of ICAM-1 did not show any apparent differences between the groups, questioning the involvement of this molecule in the early development of atherosclerosis. Plasma levels of sVCAM-1 and sICAM-1 were similar in all mice and did not correlate with the vascular gene expression...

  2. Diffuse Dermal Angiomatosis: A Clue to the Diagnosis of Atherosclerotic Vascular Disease

    Directory of Open Access Journals (Sweden)

    Tueboon Sriphojanart

    2015-05-01

    Full Text Available Diffuse dermal angiomatosis (DDA is a benign, acquired, reactive vascular proliferation. DDA is clinically characterized by painful purpuric plaque with central ulceration. The histopathologic hallmark is diffuse proliferation of endothelial cells that are arranged interstitially between collagen bundles of the reticular dermis. DDA has been reported in association with peripheral atherosclerotic disease, arteriovenous fistula and heavy smoking. We report the case of a 49-year-old Asian male with DDA who presented with a painful stellate-shaped purpuric patch on the right thigh. Histopathologic examination showed proliferation of CD34-positive spindle cells in the dermis. Our patient underwent vascular bypass surgery along with tight control of cardiovascular risk factors, which yielded successful results.

  3. Autofluorescence maps of atherosclerotic human arteries - A new technique in medical imaging

    International Nuclear Information System (INIS)

    A new medical imaging technique for arterial walls based on laser-induced autofluorescence spectroscopy is reported. The internal surface of isolated arteries with or without atherosclerosis is irradiated with an argon ion laser (458 nm) and the peak intensity of the excited autofluorescence spectrum is related to the composition of the arterial wall. The higher autofluorescence intensity in the range between approximately 480 and 630 nm for grossly calcified tissue compared to normal or noncalcified atherosclerotic tissue is used to produce maps of the arterial wall. These images delineate the calcified areas of the sample with good spatial resolution. If this technique can be adapted to the endoscopic visualization of arteries in vivo (angioscopy), it could become an important tool for the diagnosis of atherosclerosis and for the monitoring of atheroma ablation during laser angioplasty

  4. Endovascular reconstruction of iliac artery bifurcation atherosclerotic disease with the kissing technique.

    Science.gov (United States)

    Vourliotakis, Georgios; Mantas, Georgios; Katsargyris, Athanasios; Aivatidi, Christine; Kandounakis, Yannis

    2013-10-01

    A 71-year-old male patient with severe left buttock and lower-extremity claudication due to iliac artery bifurcation stenoses was referred to our institution for endovascular treatment. A 'kissing' technique was used in order to dilate the proximal parts of both internal and external iliac arteries and avoid compromization of the internal iliac artery during proximal external iliac artery stenting. A balloon expandable stent was inserted via a left ipsilateral retrograde access to the narrowed origin of the left external iliacartery and a balloon catheter via a right contralateral access inside the origin of the left internal iliac artery. Simultaneous balloons inflation restored full patency of both vessels. Twelve months later the patient is doing well, free of buttock or lower-extremity claudication symptoms. For iliac artery bifurcation atherosclerotic disease, endovascular repair with the 'kissing' technique can achieve a complete bifurcation reconstruction offering significant clinical benefit in selected patients. PMID:23493274

  5. Frequency of physical activity, exercise capacity, and atherosclerotic heart disease risk factors in male police officers.

    Science.gov (United States)

    Williams, M A; Petratis, M M; Baechle, T R; Ryschon, K L; Campain, J J; Sketch, M H

    1987-07-01

    A total of 171 male police officers volunteered to (1) assess risk factors for developing atherosclerotic heart disease and (2) evaluate the relationship of fitness to risk. Results revealed substantial numbers of officers with elevated risk: 22% were smokers, 76% had elevated cholesterol, 26% had elevated triglycerides, 16% had elevated BP, and 60% had elevated body fat. Increased fitness was associated with decreased risk. Compared with Group II (moderate fitness) or Group III (low fitness), Group I (high fitness) had significantly lower values of body fat, diastolic BP, total cholesterol, low-density lipoproteins, lipid ratios, triglycerides, and smoking incidence. Low fitness was associated with the highest prevalence of abnormal exercise tests. The results suggest (1) police officers have a high prevalence of risk and (2) increased fitness is associated with reduced risk.

  6. Immuno-modulation and anti-inflammatory benefits of antibiotics: The example of tilmicosin

    OpenAIRE

    Buret, André G.

    2010-01-01

    Exagerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokine...

  7. Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Tsutsui, H.; Tomoike, H.; Nakamura, M. (Kyushu Univ., Fukuoka (Japan))

    1990-08-01

    Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using ({sup 14}C)antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of ({sup 14}C)antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements.

  8. Effect of atorvastatin therapy on oxidant-antioxidant status and atherosclerotic plaque formation

    Directory of Open Access Journals (Sweden)

    Sezer ED

    2011-06-01

    Full Text Available Ebru Demirel Sezer1, Eser Yildirim Sozmen1, Deniz Nart2, Taner Onat11Medical Biochemistry, 2Pathology Department, Ege University School of Medicine, Izmir, TurkeyBackground: The aim of this study was to determine the oxidant–antioxidant status and lipid peroxidation products, as well as paraoxonase and atherosclerotic plaque formation, in a hypercholesterolemic atherosclerosis rabbit model to investigate the effects of atorvastatin in the atherosclerotic process.Methods: Forty male New Zealand rabbits were divided into four groups, ie, a control group receiving standard pellets, a group receiving atorvastatin therapy, a hypercholesterolemic group receiving an atherogenic diet, and a group receiving both an atherogenic diet and atorvastatin.Results: The atherogenic diet increased the levels of low-density lipoprotein (LDL thiobarbituric acid reactive substances (1.84 vs 3.79 nmol/mg protein and LDL-conjugated diene (147 vs 318 µmol/mg protein after induction of oxidation by Cu2+, despite an increase of superoxide dismutase activity. Treatment with atorvastatin limited LDL oxidation significantly (LDL thiobarbituric acid reactive substances 2.19 nmol/mg protein, LDL-conjugated diene 222 µmol/mg protein. Paraoxonase, which prevents LDL oxidation and inactivates LDL-derived oxidized phospholipids, showed a pronounced decrease in the group receiving the atherogenic diet (110 U/L to 28 U/L, and atorvastatin treatment increased paraoxonase activity. Histological examination of arcus aorta tissues from the hypercholesterolemic group showed abundant plaque formation surrounding and obstructing the lumen, whereas treatment with atorvastatin prevented or limited plaque formation, keeping the plaque thin and localized.Conclusion: Atorvastatin has dramatic antiatherosclerotic effects, part of which seems to be due to the antioxidant features of the parent drug and/or its metabolites, favoring inhibition of LDL oxidation.Keywords: atherosclerosis

  9. Atherosclerotic imaging using 4 types of superparamagnetic iron oxides: New possibilities for mannan-coated particles

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchiya, Keiko, E-mail: keikot@belle.shiga-medac.jp [Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Nitta, Norihisa, E-mail: r34nitta@yahoo.co.jp [Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Sonoda, Akinaga, E-mail: akinagasonoda@yahoo.co.jp [Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Otani, Hideji, E-mail: otani@belle.shiga-med.ac.jp [Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Takahashi, Masashi, E-mail: masashi@belle.shiga-med.ac.jp [Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Murata, Kiyoshi, E-mail: murata@belle.shiga-med.ac.jp [Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Shiomi, Masashi, E-mail: ieakusm@med.kobe-u.ac.jp [Institute for Experimental Animals, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Tyuoku, Kobe, Hyogo 650-0017 (Japan); Tabata, Yasuhiko, E-mail: yasuhiko@frontier.kyoto-u.ac.jp [Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, 53 Syogoin-Kawahara-cho, Sakyoku, Kyoto 606-8507 (Japan); Nohara, Satoshi, E-mail: s-nohara@meito-sangyo.co.jp [The Nagoya Research Laboratory, Meito Sangyo Co., Ltd., 25-5 Nishibiwajima-cho, Kiyosu, Aichi 452-0067 (Japan)

    2013-11-01

    Purpose: We used magnetic resonance imaging (MRI) and histologic techniques to compare the uptake by the rabbit atherosclerotic wall of 4 types of superparamagnetic iron oxide (SPIO) particles, i.e. SPIO, mannan-coated SPIO (M-SPIO), ultrasmall SPIO (USPIO), and mannan-coated USPIO (M-USPIO). Materials and methods: All experimental protocols were approved by our institutional animal experimentation committee. We intravenously injected 12 Watanabe heritable hyperlipidemic rabbits with one of the 4 types of SPIO (0.8 mmol Fe/kg). Two other rabbits served as the control. The rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA) before- and 5 days after these injections; excised aortae were subjected to in vitro MRI. In the in vivo and in vitro studies we assessed the signal intensity of the vessels at identical regions of interest (ROI) and calculated the signal-to-noise ratio (SNR). For histologic assessment we evaluated the iron-positive regions in Prussian blue-stained specimens. Results: There were significant differences in iron-positive regions where M-USPIO > USPIO, M-SPIO > SPIO, USPIO > SPIO (p < 0.05) but not between M-USPIO and M-SPIO. The difference between the pre- and post-injection SNR was significantly greater in rabbits treated with M-USPIO than USPIO and in rabbits injected with M-SPIO than SPIO (p < 0.05). On in vitro MRI scans SNR tended to be lower in M-USPIO- and M-SPIO- than USPIO- and SPIO-treated rabbits (p < 0.1). Conclusion: Histologic and imaging analysis showed that mannan-coated SPIO and USPIO particles were taken up more readily by the atherosclerotic rabbit wall than uncoated SPIO and USPIO.

  10. HMGB1 induces secretion of matrix vesicles which participate in microcalcification of atherosclerotic plaques

    Institute of Scientific and Technical Information of China (English)

    CHEN Qiang; BEI Jun-jie; LIU Chuan; FENG Shi-bin; ZHAO Wei-bo; ZHOU Zhou; YU Zheng-ping; DU Xiao-jun; HU Hou-yuan

    2016-01-01

    AIM:Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions .Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles ( MVs) from macrophages .METHODS:HMGB1 was added to the medium of macrophages , the secretion of MVs in the supernatant was tested by flow cytometry analysis .The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining .Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs .Then we subcutaneous injection into mice with MVs to induce regional minera-lization.RESULTS:HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis .TNAP activity, considered as a marker of MVs maturation , was higher in HMGB1-induced MVs compared to the control-MVs.HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model .Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization .Mechanistic experiments revealed that HMGB 1 activated neutral sphingomyelinase 2 ( nSMase2 ) that involved the receptor for advanced glycation end products ( RAGE ) and p38 MAPK (upstream of nSMase2).Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and min-eral deposition .CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part , via the RAGE/p38 MAPK/nSMase2 signaling pathway .Our findings thus reveal a novel mechanism by which HMGB 1 may participated in the early calcification of atherosclerotic plaques .

  11. Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits

    International Nuclear Information System (INIS)

    Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using [14C]antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of [14C]antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements

  12. Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender

    Directory of Open Access Journals (Sweden)

    Pereira Thiago MC

    2010-08-01

    Full Text Available Abstract Background Although advanced age is considered a risk factor for several diseases, the impact of gender on age-associated cardiovascular diseases, such as atherosclerotic processes and valvular diseases, remains not completely clarified. The present study was designed to assess aortic valve morphology and function and vascular damage in elderly using the apolipoprotein E knockout (ApoE KO mouse. Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice. Methods The grade (0 to 4 of aortic regurgitation was evaluated through angiography. In addition, vascular lipid deposition and senescence were evaluated through histochemical analyses in aged male and female ApoE KO mice, and the results were compared to wild-type C57BL/6J (C57 mice. Results Aortic regurgitation was observed in 92% of the male ApoE KO mice and 100% of the male C57 mice. Comparatively, in age-matched female ApoE KO and C57 mice, aortic regurgitation was observed in a proportion of 58% and 53%, respectively. Histological analysis of the aorta showed an outward (positive remodeling in ApoE KO mice (female: 1.86 ± 0.15; male: 1.89 ± 0.68 using C57 groups as reference values. Histochemical evaluation of the aorta showed lipid deposition and vascular senescence only in the ApoE KO group, which were more pronounced in male mice. Conclusion The data show that male gender contributes to the progression of aortic regurgitation and that hypercholesterolemia and male gender additively contribute to the occurrence of lipid deposition and vascular senescence in elderly mice.

  13. Importance of atherosclerotic stenotic lesion of the brachiocephalic arteries in the development of cognitive impairments

    Directory of Open Access Journals (Sweden)

    D. R. Khasanova

    2015-03-01

    Full Text Available The impact of the pattern of atherosclerotic stenotic lesion on the clinical presentation of cognitive impairments (CIs has been inadequately investigated. Objective: to estimate the impact of the degree and site of an atherosclerotic stenotic process on cerebral perfusion and cognitive functions. Patients and methods. A total of 123 patients (65 men and 58 women aged 50 to 75 years with brachiocephalic artery stenosis of at least 40%, without hypertension, diabetes mellitus, or other systemic vascular pathology were examined. The structural state of the brain substance and the state of cerebral blood flow were evaluated by magnetic resonance imaging and magnetic resonance angiography. The scale described by P. Scheltens et al. was used to determine changes in the white matter. The site and degree of a stenotic process were estimated by extracranial and transcranial duplex scanning. CIs were identified applying a set of neuropsychological assessment scales. The Hamilton hospital depression rating scale was also employed. Results and discussion. Varying degrees of CIs were detected in the majority of the examinees with brachiocephalic artery atherosclerosis. The most severe CIs were associated with the involvement of parietal and frontal lobes. There was significant deterioration in cognitive functions with a higher percentage of stenosis: more severe CIs were seen in the presence of stenosis in the carotid system than in those in the vertebrobasilar bed. In addition, the patients with concomitant stenoses and tandem stenoses were observed to have more pronounced CIs than those with single artery stenosis. Cerebral atherosclerosis is shown to be one of the major risk factors for CIs. Not only the degree of stenoses, but also to a greater extent their site was observed to impact the occurrence of CIs accompanied by the development of a perfusion deficit in the specific vascular beds. The determination of the pattern of a stenotic process will be

  14. Atherosclerotic imaging using 4 types of superparamagnetic iron oxides: New possibilities for mannan-coated particles

    International Nuclear Information System (INIS)

    Purpose: We used magnetic resonance imaging (MRI) and histologic techniques to compare the uptake by the rabbit atherosclerotic wall of 4 types of superparamagnetic iron oxide (SPIO) particles, i.e. SPIO, mannan-coated SPIO (M-SPIO), ultrasmall SPIO (USPIO), and mannan-coated USPIO (M-USPIO). Materials and methods: All experimental protocols were approved by our institutional animal experimentation committee. We intravenously injected 12 Watanabe heritable hyperlipidemic rabbits with one of the 4 types of SPIO (0.8 mmol Fe/kg). Two other rabbits served as the control. The rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA) before- and 5 days after these injections; excised aortae were subjected to in vitro MRI. In the in vivo and in vitro studies we assessed the signal intensity of the vessels at identical regions of interest (ROI) and calculated the signal-to-noise ratio (SNR). For histologic assessment we evaluated the iron-positive regions in Prussian blue-stained specimens. Results: There were significant differences in iron-positive regions where M-USPIO > USPIO, M-SPIO > SPIO, USPIO > SPIO (p < 0.05) but not between M-USPIO and M-SPIO. The difference between the pre- and post-injection SNR was significantly greater in rabbits treated with M-USPIO than USPIO and in rabbits injected with M-SPIO than SPIO (p < 0.05). On in vitro MRI scans SNR tended to be lower in M-USPIO- and M-SPIO- than USPIO- and SPIO-treated rabbits (p < 0.1). Conclusion: Histologic and imaging analysis showed that mannan-coated SPIO and USPIO particles were taken up more readily by the atherosclerotic rabbit wall than uncoated SPIO and USPIO

  15. COMBINED INTRAOPERATIVE ILIAC ARTERY STENTSAND FEMORO-POPLITEAL BYPASS FOR MULTILEVEL ATHEROSCLEROTIC OCCLUSIVE DISEASE

    Institute of Scientific and Technical Information of China (English)

    刘昌伟; 管珩; 李拥军; 郑曰宏; 刘卫

    2001-01-01

    Objective. To review our preliminary experience and evaluate our early results of a combined intraopemtive iliac angioplasty and stenting with infrainguinal revascularization in multilevel atherosclerotic occlusive disease. Methods. From July 1999 to April 2000, intraoperative iliac angiOplasty and stenting combined with simultaneous femoro-pepliteal bypass were pedormed on 12 lower extremities of 10 patients suffering from multilevel athemsclemtic occlusive disease. There were 8 men and 2 women, average 72 years. The indicationsf or procedures included disabling claudication in 3 and rest pain in 7 patients. Results. Eleven iliac angioplasty and stem procedures combined with simultaneous 9 femoro-popliteal by-pass and 3 femoro-femoral-popliteal bypass were performed in 12 limbs of 10 patients. Angioplasty and stem placement was technically successful in all patients. One contralateral femoral-popliteal bypass was failure after femoro-femoral-popliteal bypass. There were no additional instances of procedural or postoperative morbidity or mortality. Mean follow-up was 5 months (range 1 -10 months). During the follow-up period, one femoro-infrapoplitealgraft became occluded after 7 months and above-knee amputation was required. The cumulative primary patencyrate of stented iliac arteries, femoro-femoral bypass grafts and femoro-popliteal bypass grafts were 100% (11/11), 100% (3/3) and 90. 9% (10/11) in the follow-up period, respectivdy. The amputation rate was 8. 3%(1/12). Conclusions. Intraoperative iliac artery PTA and stent placement can be safely and effectively pedormed simultaneously with infrainguinal revascularization for multilevel atherosclerotic occlusive disease by skilled vascular surgeon, using a portable C ann fluoroscopy in the operating room. Furthermore, iliac artery PTA and stenting was valuable adjunct to distal bypass either to improve inflow and outflow, or to reduce the extent of traditionalsurgical intervention, and also, any angioplasty and

  16. Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone IIA on atherosclerosis.

    Science.gov (United States)

    Li, Yujie; Guo, Yan; Chen, Ying; Wang, Yajie; You, Yun; Yang, Qing; Weng, Xiaogang; Li, Qi; Zhu, Xiaoxin; Zhou, Bingbing; Liu, Xucen; Gong, Zaipeng; Zhang, Ruijie

    2015-08-01

    Increasing evidence supports the hypothesis that inflammatory reactions serves an important function in the formation, progression and plaque rupture of atherosclerosis. Interleukin (IL)-1 primarily induces inflammation and is closely associated with the inflammatory environment and the formation of atherosclerosis. The present study aimed to establish an in vitro model for the evaluation of drug efficacy in the intervention of atherosclerosis from the inflammatory perspective, and to observe the anti-inflammatory effects of tanshinone IIA and andrographolide on atherosclerosis. The IL-1β-induced inflammation-activated endothelial cell (EC)-smooth muscle cell (SMC)-mononuclear cell (MC) co-culture model was established, based on the changes in a series of atherosclerosis-associated inflammatory markers secreted by ECs and SMCs. The expression of connexin in ECs, adhesion of MCs and changes in inflammatory signalling molecules were selected as evaluation indices for the inflammatory microenvironment of atherosclerosis. The use of this model revealed that tanshinone IIA exhibited significant efficacy against atherosclerosis and its inflammatory reactions. Inflammatory reactions were regarded as the primary mechanism underlying atherosclerosis. The established model simulated a series of relevant changes in the arterial wall under the inflammatory cytokines with oxidized low-density lipoprotein during the atherosclerotic process. The present study presented a reliable method for the identification of drugs with potential anti-inflammatory activity in atherosclerosis, for investigating the mechanisms of action, considering the improvement of the inflammatory state and the increase in plaque stability observed. PMID:25936371

  17. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo;

    2013-01-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class...

  18. [Present Execution of and Problems with Clinical Lipid Examination and Application of "the Japan Atherosclerotic Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012"].

    Science.gov (United States)

    Igarashi, Masahiko; Tanji, Yasuhiro; Nomura, Takashi; Yamaguchi, Hiroshi

    2014-09-01

    It is well known that dyslipidemia is one of the most crucial risk factors for atherosclerosis, including cardiovascular diseases (ASCVD). In order to prevent the onset of ASCVD, the Japan Atherosclerotic Society (JAS) published the JAS Guidelines in 2012 for appropriate lipid examination and treatment. However, it is unknown how the guidelines are practically used by Japanese clinicians. Therefore, we conducted a questionnaire survey to assess the present execution of and problems with clinical lipid examination and the application of the JAS Guidelines by doctors working in hospitals and clinics of Yamagata district in Japan. We found that 16% of doctors carried out clinical lipid examination every time, but some did not examine lipids at all. Fasting blood sampling for lipid examination was performed by 44% of doctors, and the items of triglycerides, HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) were measured by more than 95%. Regarding problems with clinical lipid examination, more than 40% of doctors requested the early achievement of the standardization of LDL-C. The JAS Guidelines in 2012 were unfortunately recognized by only 55% of doctors. In addition, the rate of the clinical application of the guidelines, including the absolute risk, the flowchart of LDL-C, and non-HDL-C, was less than 30%, and more than half of the doctors measured LDL-C with the direct method, but did not use the "recommended" Friedewald method. In contrast, the cardiologists and endocrinologists generally accepted the guidelines, and their clinical application rate was higher than in other doctors. Through the questionnaire survey, it was revealed that doctors in various fields have not properly accepted the use and significance of lipid examination and the JAS Guidelines, and so further educational activities are necessary. PMID:27526534

  19. Inflammatory pseudotumor of the parotid gland.

    Science.gov (United States)

    Barrios-Sánchez, Gracia M; Dean-Ferrer, Alicia; Alamillos-Granados, Francisco J; Ruiz-Masera, Juan José; Zafra-Camacho, Francisco M; García de Marcos, José A; Calderón-Bohórquez, José M

    2005-01-01

    Inflammatory pseudotumor is a term that refers to a reactive pseudoneoplastic disorder that can appear in different locations of the human body. The lung is the most frequently affected organ. The etiology is still unknown. It affects individuals of both sexes and of a wide range of ages. The diagnosis is still difficult and it is based on the histological examination of the lesions composed of four cell-types: histiocytes, myofibroblasts, plasma cells and lymphocytes. With regard to the treatment regimes there is no agreement. Treatment ranges from surgical excision to radiotherapy, chemotherapy or steroids. The purpose of this article is to report one case of inflammatory pseudotumor located in the parotid gland and to make a special point of the difficulty in arriving at a correct diagnosis in order to achieve the most adequate treatment.

  20. Primary culture of endothelial cells from atherosclerotic human aorta. Part 1. Identification, morphological and ultrastructural characteristics of two endothelial cell subpopulations.

    Science.gov (United States)

    Antonov, A S; Nikolaeva, M A; Klueva, T S; Romanov YuA; Babaev, V R; Bystrevskaya, V B; Perov, N A; Repin, V S; Smirnov, V N

    1986-01-01

    Endothelial cells (EC) were harvested by 0.1% collagenase treatment for adult human thoracic aortas obtained 1-3 h after sudden death. At least 35-70% of EC were removed from the intimal surface of aorta, 90-95% of them being viable. Plating efficiency was 70-80%. Monolayer formation was achieved at a seeding density of 5-8 X 10(2) cells/mm2. The cells were identified as endothelium by the presence of Factor VIII antigen, Weigel-Palade bodies and typically endothelial morphology at confluence. Unlike endothelial cultures derived from human umbilical veins and infant aortas, primary cultures obtained from human adult aortas contain multinuclear EC with Factor VIII antigen and Weibel-Palade bodies. The number of multinuclear EC in cultures isolated from aortas affected by atherosclerosis was 2-fold higher (P less than 0.05) than in cultures obtained from grossly normal aortas taken from donors of the same age. EC with numerous lipid inclusions revealed by oil-red-O staining were present in all the EC primary cultures derived from aortas affected by atherosclerosis. No oil-red-O-positive cells were detected among the EC cultured from infant aorta, aorta of young donors, and umbilical vein. An electron microscopic examination of EC from atherosclerotic aorta in culture and in situ failed to reveal any ultrastructural peculiarities distinguishing multinuclear EC from the mononuclear EC. PMID:3004520

  1. Characterization of human arterial tissue affected by atherosclerosis using multimodal nonlinear optical microscopy

    Science.gov (United States)

    Baria, Enrico; Cicchi, Riccardo; Rotellini, Matteo; Nesi, Gabriella; Massi, Daniela; Pavone, Francesco S.

    2016-03-01

    Atherosclerosis is a widespread cardiovascular disease caused by the deposition of lipids (such as cholesterol and triglycerides) on the inner arterial wall. The rupture of an atherosclerotic plaque, resulting in a thrombus, is one of the leading causes of death in the Western World. Preventive assessment of plaque vulnerability is therefore extremely important and can be performed by studying collagen organization and lipid composition in atherosclerotic arterial tissues. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires immune-histochemical examination and a morpho-functional approach. Instead, a label-free and non-invasive alternative is provided by nonlinear microscopy. In this study, we combined SHG and FLIM microscopy in order to characterize collagen organization and lipids in human carotid ex vivo tissues affected by atherosclerosis. SHG and TPF images, acquired from different regions within atherosclerotic plaques, were processed through image pattern analysis methods (FFT, GLCM). The resulting information on collagen and cholesterol distribution and anisotropy, combined with collagen and lipids fluorescence lifetime measured from FLIM images, allowed characterization of carotid samples and discrimination of different tissue regions. The presented method can be applied for automated classification of atherosclerotic lesions and plaque vulnerability. Moreover, it lays the foundation for a potential in vivo diagnostic tool to be used in clinical setting.

  2. SPECT radiopharmaceuticals for imaging chronic inflammatory diseases in the last decade

    International Nuclear Information System (INIS)

    In the recent years, many radiopharmaceuticals have been described for the diagnosis of inflammatory chronic diseases. Several peptides, receptor ligands and monoclonal antibodies have been radiolabelled, allowing in-vivo visualization of inflammatory processes at a cellular and molecular level. The labelling of cytokines such as interleukin-1, interleukin-2, interleukin-12 and MCP-1 has facilitated the identification of inflamed synovia in patients with rheumatoid arthritis, active Crohn’s disease, vulnerable atherosclerotic plaques and other targets. The possibility of using monoclonal antibodies against TNF-α, CD2, CD3, CD4 and anti-selectin has not only allowed the localization of inflamed sites but had also a significant impact in helping the selection of patients who can benefit from biological therapies. Regarding radiolabelled peptides, it is important to highlight the increasing use of somatostatin analogues targeting somatostatin receptors in inflammatory diseases, particularly for rheumatoid arthritis, Sjögren syndrome and autoimmune thyroid diseases. In the present review we describe the state of the art of SPECT radiopharmaceuticals to image chronic inflammatory diseases.

  3. Retroperitoneal inflammatory myofibroblastic tumor

    Directory of Open Access Journals (Sweden)

    Bapsy Poonamalle P

    2005-10-01

    Full Text Available Abstract Background Inflammatory myofibroblastic tumor (IMT is a neoplasm of unknown etiology occurring at various sites. By definition, it is composed of spindle cells (myofibroblasts with variable inflammatory component, hence the name is IMT. Case presentation The present case is of a 46 years old woman presented with a history of flank pain, abdominal mass and intermittent hematuria for last 6 months. The initial diagnosis was kept as renal cell carcinoma. Finally, it turned out to be a case of retroperitoneal IMT. The patient was managed by complete surgical resection of the tumor. Conclusion IMT is a rare neoplasm of uncertain biological potential. Complete surgical resection remains the mainstay of the treatment.

  4. Inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Kottler, R.E.; Freson, M. (Groote Schuur Hospital, Cape Town (South Africa). Dept. of Radiology)

    1985-06-01

    Radiology is of considerable value in all forms of inflammatory bowel disease to establish its presence and extent, and to differentiate lesions. The most common inflammatory bowel diseases are Crohn's disease and ulcerative colitis. Crohn's disease may occur anywhere in the disgestive tract, but is most common in the terminal ileum. Since there is no practical endoscopic method of examining the small bowel, barium studies of the latter are most important. Modern radiological techniques, especially the double contrast barium enema, show excellent correlation between the macroscopic changes and the radiological features. Radiology alone does not provide the answers and the radiological features must be interpreted in conjunction with clinical investigation.

  5. Association between plasma inflammatory markers and morphology of coronary artery lesion in patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Xian Wang; Dayi Hu; Shiwei Yang; Jian Zhang; Tan Chen; Shouyan Zhang

    2008-01-01

    The atherosclerotic plaque vulnerability may be related to inflammation,immunity,metabolism and blood clotting.One of the key factors affecting plaque stability is inflammatory reaction.This study was to investigate the relationship between vulnerability of coronary artery plaque evaluated with coronary angiography (CAG),intravascular ultrasound (IVUS) and the levels of plasma inflammatory markers.Methods Fifty-eight consecutive patients with acute coronary syndrome who had coronary lesion of a single vessel were divided into 3 groups based on angiographic morphology of the lesions:type Ⅰ lesion group (n =16),type Ⅱ lesion group (n =25) and type Ⅲ lesion group (n =17).The control group consisted of 17 patients with stable angina.Plasma levels of high sensitivity C reaction protein (hs-CRP),matrix metalloproteinase (MMP,including MMP-2 and MMP-9),CD40 ligand (CD40L) and pregnancy associated plasma protein-A (PAPP-A) were measured by ELISA.A subgroup of 28 patients (including 18 ACS patients and 10 stable angina control patients) who underwent IVUS study,were analyzed.Results The plasma levels of MMP-2,MMP-9 and PAPP-A in type Ⅱ lesion group were significantly higher than those in other groups (all P<0.05).In type Ⅱ lesion group,linear correlation analyses showed significant positive correlation between levels of hs-CRP and MMP-2 (r=0.508);MMP-2 and MMP-9,CD40L,PAPP-A (r=0.647,0.704 and 0.751,respectively);MMP-9 and CD40L,PAPP-A (r=0.491 and 0.639,respectively);CD40L and PAPP-A (r=0.896).IVUS subgroup analysis showed that the area of plaques and plaque burden in culprit lesion,the incidence of high-risk plaques,remodeling index (RI) and positive remodeling percentage in ACS patients were significantly greater than those in control subgroup (P=0.000,0.037,0.028,0.015 and 0.040,respectively).Compared with control subgroup,the plasma levels of hs-CRP,MMP-2,MMP-9 and PAPP-A were markedly elevated (P=0.033,0.000,0.000 and 0.027,respectively).Conclusions CAG

  6. Chronic inflammatory systemic diseases

    OpenAIRE

    Straub, Rainer H.; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history sta...

  7. Inflammatory mediators in osteoarthritis

    OpenAIRE

    M Beekhuizen

    2014-01-01

    Osteoarthritis (OA) is a degenerative joint disorder involving cartilage destruction and joint inflammation. Despite extensive research, still much is unknown on the pathogenesis and aetiology of OA. Inflammation and inflammatory mediators (both local and systemic) are key in the pathogenesis of OA. For rheumatoid arthritis, multiple therapies are based on targeting the mediators that are associated with inflammation and joint destruction. Motivated by these findings we set off to identify wh...

  8. [Inflammatory abdominal aortic aneurysm].

    Science.gov (United States)

    Ziaja, K; Sedlak, L; Urbanek, T; Kostyra, J; Ludyga, T

    2000-01-01

    The reported incidence of inflammatory abdominal aortic aneurysm (IAAA) is from 2% to 14% of patients with abdominal aortic aneurysm and the etiology of this disease is still discussed--according to the literature several pathogenic theories have been proposed. From 1992 to 1997 32 patients with IAAA were operated on. The patients were mostly symptomatic--abdominal pain was present in 68.75% cases, back pain in 31.25%, fever in 12.5% and weight loss in 6.25% of the operated patients. In all the patients ultrasound examination was performed, in 4 patients CT and in 3 cases urography. All the patients were operated on and characteristic signs of inflammatory abdominal aortic aneurysm like: thickened aortic wall, perianeurysmal infiltration or retroperitoneal fibrosis with involvement of retroperitoneal structures were found. In all cases surgery was performed using transperitoneal approach; in three cases intraoperatively contiguous abdominal organs were injured, which was connected with their involvement into periaortic inflammation. In 4 cases clamping of the aorta was done at the level of the diaphragmatic hiatus. 3 patients (9.37%) died (one patient with ruptured abdominal aortic aneurysm). Authors present diagnostic procedures and the differences in the surgical tactic, emphasizing the necessity of the surgical therapy in patients with inflammatory abdominal aortic aneurysm.

  9. Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals.

    Science.gov (United States)

    Bagalkot, Vaishali; Badgeley, Marcus A; Kampfrath, Thomas; Deiuliis, Jeffrey A; Rajagopalan, Sanjay; Maiseyeu, Andrei

    2015-11-10

    Macrophages are innate immune cells with great phenotypic plasticity, which allows them to regulate an array of physiological processes such as host defense, tissue repair, and lipid/lipoprotein metabolism. In this proof-of-principle study, we report that macrophages of the M1 inflammatory phenotype can be selectively targeted by model hybrid lipid-latex (LiLa) nanoparticles bearing phagocytic signals. We demonstrate a simple and robust route to fabricate nanoparticles and then show their efficacy through imaging and drug delivery in inflammatory disease models of atherosclerosis and obesity. Self-assembled LiLa nanoparticles can be modified with a variety of hydrophobic entities such as drug cargos, signaling lipids, and imaging reporters resulting in sub-100nm nanoparticles with low polydispersities. The optimized theranostic LiLa formulation with gadolinium, fluorescein and "eat-me" phagocytic signals (Gd-FITC-LiLa) a) demonstrates high relaxivity that improves magnetic resonance imaging (MRI) sensitivity, b) encapsulates hydrophobic drugs at up to 60% by weight, and c) selectively targets inflammatory M1 macrophages concomitant with controlled release of the payload of anti-inflammatory drug. The mechanism and kinetics of the payload discharge appeared to be phospholipase A2 activity-dependent, as determined by means of intracellular Förster resonance energy transfer (FRET). In vivo, LiLa targets M1 macrophages in a mouse model of atherosclerosis, allowing noninvasive imaging of atherosclerotic plaque by MRI. In the context of obesity, LiLa particles were selectively deposited to M1 macrophages within inflamed adipose tissue, as demonstrated by single-photon intravital imaging in mice. Collectively, our results suggest that phagocytic signals can preferentially target inflammatory macrophages in experimental models of atherosclerosis and obesity, thus opening the possibility of future clinical applications that diagnose/treat these conditions. Tunable Li

  10. Prescription Nonsteroidal Anti-Inflammatory Medicines

    Science.gov (United States)

    MENU Return to Web version Prescription Nonsteroidal Anti-Inflammatory Medicines Prescription Nonsteroidal Anti-Inflammatory Medicines How do prescription nonsteroidal anti-inflammatory drugs work? Nonsteroidal anti-inflammatory drugs (also called NSAIDs) stop cyclooxygenase ...

  11. Psychosocial factors in peptic ulcer and inflammatory bowel disease.

    Science.gov (United States)

    Levenstein, Susan

    2002-06-01

    Over the past decade, while gastroenterologists' interest in mind-body interactions in organic disorders dwindled, stronger evidence has linked psychosocial factors with the incidence and recurrence of peptic ulcer and with the course of inflammatory bowel disease. Psychological-behavioral approaches to treatment continue to be disappointing. Psychosocial factors may affect ulcer by increasing duodenal acid load, altering local circulation or motility, intensifying Helicobacter pylori infection, stimulating corticosteroid secretion, and affecting health risk behaviors; possible mechanisms for inflammatory bowel disease include immune deregulation, gut permeability changes, and poor medication adherence. Both belong to the growing category of diseases thought to have an infectious component: for peptic ulcer the bacterium Helicobacter pylori, for inflammatory bowel disease an exaggerated immune response to gut bacteria. Peptic ulcer and inflammatory bowel disease, which present unique interactions among psychological, immunologic, endocrine, infectious, and behavioral factors, are splendid paradigms of the biopsychosocial model.

  12. Tiaozhi Tongmai Granules reduce atherogenesis and promote the expression of ATP-binding cassette transporter A1 in rabbit atherosclerotic plaque macrophages and the liver

    Directory of Open Access Journals (Sweden)

    Qing Sun

    2014-07-01

    Conclusions: Tiaozhi Tongmai Granules appear to have an anti-atherogenic effect that is most likely mediated by simultaneously upregulating the protein expression of ABCA1 in rabbit atherosclerotic plaque macrophages and in the liver.

  13. Inflammatory Process in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    MARCO ANTONIO eMERAZ RIOS

    2013-08-01

    Full Text Available Alzheimer Disease (AD is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFTs and extracellular neuritic plaques (NPs surrounded by activated astrocytes and microglia. NFTs consist of paired helical filaments of truncated tau protein that is abnormally hyperphosphorylated. The main component in the NP is the amyloid-β peptide (Aβ, a small fragment of 40-42 amino acids with a molecular weight of 4kD. It has been proposed that the amyloid aggregates and microglia activation are able to favor the neurodegenerative process observed in AD patients. However, the role of inflammation in AD is controversial, because in early stages the inflammation could have a beneficial role in the pathology, since it has been thought that the microglia and astrocytes activated could be involved in Aβ clearance. Nevertheless the chronic activation of the microglia has been related with an increase of Aβ and possibly with tau phosphorylation. Studies in AD brains have shown an upregulation of complement molecules, pro-inflammatory cytokines, acute phase reactants and other inflammatory mediators that could contribute with the neurodegenerative process. Clinical trials and animal models with nonsteroidal anti-inflammatory drugs (NSAIDs indicate that these drugs may decrease the risk of developing AD and apparently reduce Aβ deposition. Finally, further studies are needed to determine whether treatment with anti-inflammatory strategies, may decrease the neurodegenerative process that affects these patients.

  14. Antiangiogenic VEGF Isoform in Inflammatory Myopathies

    Directory of Open Access Journals (Sweden)

    Nila Volpi

    2013-01-01

    Full Text Available Objective. To investigate expression of vascular endothelial growth factor (VEGF antiangiogenic isoform A-165b on human muscle in idiopathic inflammatory myopathies (IIM and to compare distribution of angiogenic/antiangiogenic VEGFs, as isoforms shifts are described in other autoimmune disorders. Subjects and Methods. We analyzed VEGF-A165b and VEGF-A by western blot and immunohistochemistry on skeletal muscle biopsies from 21 patients affected with IIM (polymyositis, dermatomyositis, and inclusion body myositis and 6 control muscle samples. TGF-β, a prominent VEGF inductor, was analogously evaluated. Intergroup differences of western blot bands density were statistically examined. Endomysial vascularization, inflammatory score, and muscle regeneration, as pathological parameters of IIM, were quantitatively determined and their levels were confronted with VEGF expression. Results. VEGF-A165b was significantly upregulated in IIM, as well as TGF-β. VEGF-A was diffusely expressed on unaffected myofibers, whereas regenerating/atrophic myofibres strongly reacted for both VEGF-A isoforms. Most inflammatory cells and endomysial vessels expressed both isoforms. VEGF-A165b levels were in positive correlation to inflammatory score, endomysial vascularization, and TGF-β. Conclusions. Our findings indicate skeletal muscle expression of antiangiogenic VEGF-A165b and preferential upregulation in IIM, suggesting that modulation of VEGF-A isoforms may occur in myositides.

  15. Mechanistic similarities between trauma, atherosclerosis, and other inflammatory processes.

    Science.gov (United States)

    Scalea, Joseph R; Bromberg, Jonathan; Bartlett, Stephen T; Scalea, Thomas M

    2015-12-01

    Most human diseases, including trauma, atherosclerosis, and malignancy, can be characterized by either an overexuberant inflammatory response or an inadequate immunologic response. As our understanding of the mechanisms underlying these inflammatory aberrations improves, so should our approach to the patient. The development of novel technologies capable of exploiting inflammatory mediators will undoubtedly play a role in future patient-directed therapies. Trauma surgeons are uniquely positioned to usher in a new era of patient diagnostics and patient-directed therapies based on an understanding of the immune system's response to stimuli. These improvements are likely to affect not only trauma care but all aspects of medicine. PMID:26304513

  16. Significance of ultrasound evaluation of carotid atherosclerotic plaque for diagnosing ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Carotid artery is the main source for craniocerebral blood supply. Its intimal plaque formation and arterial stenosis degree both are the risk factors for ischemic cerebrovascular disease.Therefore, the close relationship of carotid atherosclerotic plaque and ischemic cerebrovascular disease, and ultrasound evaluation of carotid atherosclerotic plaque have become the hot spot in studying ischemic cerebrovascular disease.OBJECTIVE: This study was to detect the degree of carotid atherosclerosis of ischemic cerebrovascular disease patients by ultrasonography, and to analyze the situation of carotid atherosclerosis and its relationship with clinic.DESIGN: Clinical randomized concurrent control experiment.SETTING: Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS: Totally 60 outpatients and inpatients with ischemic cerebrovascular disease, 42 males and 18 females, admitted to Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA between January 2006 and December 2006 were involved in the patient group. They met the diagnosis criteria of ischemic cerebrovascular disease constituted by the 4th Cerebrovascular Disease Conference in 1996, and were confirmed to suffer from ischemic cerebrovascular disease by skull CT and MRI. Another 20 subjects who received healthy examination concurrently in the same hospital, 12 males and 8 females, were involved in the control group. Informed consents of detected items were obtained from involved subjects.METHODS: The plaque thickness of mid portion, distal end and crotch of common carotid artery (CCA),internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA) of involved subjects,who received health examination was separately detected with color Doppler ultrasonograph (HDI-5000).Then, total integral of plaque was calculated. The intima-media thickness (IMT) was measured with two-dimensional ultrasonography. The inner diameter

  17. Atherosclerotic Risk Factors and Their Association With Hospital Mortality Among Patients With First Myocardial Infarction (from the National Registry of Myocardial Infarction)

    OpenAIRE

    Canto, John G.; Kiefe, Catarina I.; Rogers, William J.; Peterson, Eric D.; Frederick, Paul D.; French, William J.; Gibson, C. Michael; Pollack, Charles V; Ornato, Joseph P.; Zalenski, Robert J.; Penney, Jan; Tiefenbrunn, Alan J.; Greenland, Philip

    2012-01-01

    Few studies have examined associations between atherosclerotic risk factors and short-term mortality after first myocardial infarction (MI). Histories of 5 traditional atherosclerotic risk factors at presentation (diabetes, hypertension, smoking, dyslipidemia, and family history of premature heart disease) and hospital mortality were examined among 542,008 patients with first MIs in the National Registry of Myocardial Infarction (1994 to 2006). On initial MI presentation, history of hypertens...

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

    OpenAIRE

    Grool, Anne M; Yolanda van der Graaf; Witkamp, Theo D.; Vincken, Koen L.; Mali, Willem P. T. M.; Geerlings, Mirjam I.

    2011-01-01

    Objectives. Mechanisms influencing the course of physical and mental functioning after an atherosclerotic event are unclear. We examined effects of white matter lesion (WML) activity on changes in functioning in patients with symptomatic atherosclerotic disease. Methods. In 486 patients (58 ± 9 years) of the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, volumetric WML measurements on 1.5T MRI were performed at baseline and 3.9 ± 0.4 years followup. Functioning...

  19. Short-term effect of severe exposure to methylmercury on atherosclerotic heart disease and hypertension mortality in Minamata.

    Science.gov (United States)

    Inoue, Sachiko; Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

    2012-02-15

    Recent studies suggest potential adverse effects of methylmercury exposure on myocardial infarction and hypertension, although the evidence is still limited. We thus evaluated this association using age-standardized mortality ratios (ASMRs) in Minamata, where severe methylmercury poisoning had occurred. We obtained mortality data from annual vital statistics and demographic statistics from census. We then compared mortality of atherosclerotic heart disease including degenerative heart disease and hypertension in Minamata-city with those in Kumamoto Prefecture, which includes Minamata city, as a control. We estimated ASMRs and 95% confidence intervals (CIs) during the period from 1953 to 1970. ASMRs of atherosclerotic heart disease were continuously decreased during the period from 1953 to 1967. In contrast, the ASMR of hypertension was significantly elevated during the period from 1963 to 1967 (SMR=1.38, CI; 1.06-1.80); but they decreased later. Although dilution is present in this ecological study, our study supports the notion that methylmercury exposure induces hypertension.

  20. Inflammatory bowel disease unclassified

    Institute of Scientific and Technical Information of China (English)

    Ning ZHOU; Wei-xing CHEN; Shao-hua CHEN; Cheng-fu XU; You-ming LI

    2011-01-01

    Objective: Inflammatory bowel diseases (IBDs) are idiopathic, chronic, and inflammatory intestinal disorders. The two main types, ulcerative colitis (UC) and Crohn's disease (CD), sometimes mimic each other and are not readily distinguishable. The purpose of this study was to present a series of hospitalized cases, which could not initially be classified as a subtype of IBD, and to try to note roles of the terms indeterminate colitis (IC) and inflammatory bowel disease unclassified (IBDU) when such a dilemma arises. Methods: Medical records of 477 patients hospitalized due to IBD, during the period of January 2002 to April 2009, were retrospectively studied in the present paper. All available previous biopsies from endoscopies of these patients were reanalyzed. Results: Twenty-seven of 477 IBD patients (5.7%) had been initially diagnosed as having IBDU. Of them, 23 received colonoscopy and histological examinations in our hospital. A total of 90% (9/10) and 66.7% (4/6) of patients, respectively, had a positive finding via wireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE). The barium-swallow or small bowel follow-through (SBFT) was performed on 11 patients. Positive changes were observed under computer tomographic (CT) scanning in 89.5% (17/19) of patients. Reasonable treatment strategies were employed for all patients. Conclusions: Our data indicate that IBDU accounts for 5.7% of initial diagnoses of IBD. The definition of IBDU is valuable in clinical practice. For those who had no clear clinical, endoscopic, histological, or other features affording a diagnosis of either UC or CD,IBDU could be used parenthetically.

  1. Vascular morphologic and functional effect of endogenous androgens in an experimental atherosclerotic rabbits model

    International Nuclear Information System (INIS)

    Previous clinical and experimental studies suggest that androgens could have adverse, neutral or beneficial effect on atherosclerosis and its clinical manifestations. Methods: an experimental, randomized controlled study in 40 New Zeland white male rabbits was realized. 20 rabbits underwent orchidectomy and 20 were fed with an atherogenic diet for 20 weeks. These were distributed in four groups: 1. non-castrated under normal diet, 2. Castrated under normal diet, 3. non-castrated under atherogenic diet, and 4. Castrated under atherogenic diet. Total cholesterol and free testosterone were measured. After euthanasia, arterial relaxation independent of endothelium was quantified in aorta, as well as the one depending on endothelium, in vitro, and histomorphometric analysis of thoracic aorta were made in order to quantify the atherosclerotic plaque formation. Results: animals that had a normal diet (n=20) had total cholesterol of 51.1 ± 8.5 mg/dl and those with atherogenic diet of 429.2 ± 262.0 mg/dl (p< 0.001). Testosterone levels in the non- castrated group were 2.1 ± 0.3 ng/ml and in the castrated were 0.8 ± 0.4 ng/ml (p= 0.024). In non-castrated rabbits the effect of hypercholesterolemia (366 ± 226.1 mg/dl) inducing atherosclerotic plaque and functional vascular alteration was mild. On the other hand, atherogenic diet in castrated rabbits induced an increment in total cholesterol from 387.6 ± 292.7 mg/dl (p <0.001) and severe morphological changes such as plaque area 2.6 ± 2.3mm (p <0.001), vessel plaque/area 0.25 ± 0.1 (p <0.001) and area index of plaque/area of the media 0.4 ± 0.3 (p <0.001). Endothelium independent relaxation percentage was 85.5 ± 14.3% (p = NS) and endothelium dependent relaxation was 38.5 ± 201% (p = 0.03). Conclusion: This study realized in rabbits demonstrates that endogenous testosterone might have a preventive effect on atherosclerosis and favor endothelium dependent vascular relaxation in the presence of severe

  2. Vitamin D Supplementation Reduces Intimal Hyperplasia and Restenosis following Coronary Intervention in Atherosclerotic Swine

    Science.gov (United States)

    Gupta, Gaurav K.; Agrawal, Tanupriya; Rai, Vikrant; Del Core, Michael G.; Hunter, William J.

    2016-01-01

    Vitamin D is a fat-soluble steroid hormone that activates vitamin D receptor to regulate multiple downstream signaling pathways and transcription of various target genes. There is an association between vitamin D deficiency and increased risk for cardiovascular disease. However, most of the studies are observational and associative in nature with limited data on clinical application. Thus, there is a need for more prospective randomized controlled studies to determine whether or not vitamin D supplementation provides cardiovascular protection. In this study, we examined the effects of the deficiency and supplementation of vitamin D on coronary restenosis following coronary intervention in atherosclerotic Yucatan microswine. Twelve Yucatan microswine were fed vitamin D-deficient (n = 4) or -sufficient (n = 8) high cholesterol diet for 6-months followed by coronary intervention. Post-intervention, swine in the vitamin D-sufficient high cholesterol diet group received daily oral supplementation of either 1,000 IU (n = 4) or 3,000 IU (n = 4) vitamin D3. Six months later, optical coherence tomography (OCT) was performed to monitor the development of intimal hyperplasia and restenosis. Animals were euthanized to isolate arteries for histomorphometric and immunohistochemical studies. Animals had graded levels of serum 25(OH)D; vitamin D-deficient (15.33 ± 1.45 ng/ml), vitamin D-sufficient + 1,000 IU oral vitamin D post-intervention (32.27 ± 1.20 ng/ml), and vitamin D-sufficient + 3,000 IU oral vitamin D post-intervention (51.00 ± 3.47 ng/ml). Findings from the OCT and histomorphometric studies showed a decrease in intimal hyperplasia and restenosis in vitamin D-supplemented compared to vitamin D-deficient swine. Vitamin D supplementation significantly decreased serum levels of TNF-α and IFN-γ, upregulated serum levels of IL-10, and had no effect on serum IL-6 levels. These findings suggest that vitamin D supplementation limits neointimal formation following coronary

  3. Anti-inflammatory Activity.

    Science.gov (United States)

    2016-01-01

    Inflammation is the body's first response to infection or injury and is critical for both innate and adaptive immunity. It can be considered as part of the complex biological response of vascular tissues to harmful stimuli such as pathogens, damaged cells, or irritants. The search for natural compounds and phytoconstituents that are able to interfere with these mechanisms by preventing a prolonged inflammation could be useful for human health. Here, the anti-inflammatory properties of plant-based drugs are put together with both in vitro and acute (carrageenan, egg albumin and croton oil) and chronic (cotton pellet) in vivo models. PMID:26939273

  4. Chronic inflammatory demyelinative polyneuropathy

    DEFF Research Database (Denmark)

    Said, Gérard; Krarup, Christian

    2013-01-01

    Chronic inflammatory demyelinative polyneuropathy (CIDP) is an acquired polyneuropathy presumably of immunological origin. It is characterized by a progressive or a relapsing course with predominant motor deficit. The diagnosis rests on the association of non-length-dependent predominantly motor...... deficit following a progressive or a relapsing course associated with increased CSF protein content. The demonstration of asymmetrical demyelinating features on nerve conduction studies is needed for diagnosis. The outcome depends on the amplitude of axon loss associated with demyelination. CIDP must...... be differentiated from acquired demyelinative neuropathies associated with monoclonal gammopathies. CIDP responds well to treatment with corticosteroids, intravenous immunoglobulins, and plasma exchanges, at least initially....

  5. Kirsner's inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    R Balfour Sarto; William J Sandborn

    2005-01-01

    @@ Very few medical textbooks have so thoroughly dominated,and even defined a field, as has Inflammatory Bowel Diseases by Joe Kirsner. Originally co-edited with Roy Shorter of Mayo Clinic, this book, beginning with its first edition in 1975, encapsulated the science and art of caring for patients with Crohn's disease and ulcerative colitis. Thus it is with considerable respect, and indeed some awe and trepidation,that we eagerly embraced the opportunity to assume the editorship of this preeminent textbook and the obligation to transition it to reflect the changing, increasingly complex pathophysiology and treatment of these diseases.

  6. INFLAMMATORY BOWEL DISEASE

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Mahaprani Danastri

    2013-02-01

    Full Text Available Crohn disease (CD and ulcerative colitis (UC is an chronic inflammation in the gastrointestinal tract. Colecctively, they are called inflammatory bowel disease (IBD, and about 1,5 millions people in America suffering from UC and CD. The cause of UC and CD is unknown, but the expert believe that UC and CD are caused by a disturbed immune response in someone who has a genetic predisposition. UC and CD have a significant recurrency  and remission rate. Surgery in UC is a curative treatment for colon’s disease and a potentially colon’s malignancy, but it is not a curative treatment for CD.

  7. Local blood pressure associates with the degree of luminal stenosis in patients with atherosclerotic disease in the middle cerebral artery

    OpenAIRE

    Jiang, Yuanliang; Peng, Wenjia; Teng, Zhongzhao; Gillard, Jonathan H.; Hong, Bo; Liu, Qi; Lu, Jianping

    2016-01-01

    The mechanism underlying atherosclerotic ischemic events within the middle cerebral artery (MCA) is unclear. High structural stress induced by blood pressure might be a potential aetiology as plaque rupture occurs when such mechanical loading exceeds its material strength. To perform reliable analyses quantifying the mechanical loading within a plaque, the local blood pressure is needed. However, data on MCA blood pressure is currently lacking. In this study, the arterial pressure proximal to...

  8. Berberine inhibits inflammatory activation of rat brain microglia

    Institute of Scientific and Technical Information of China (English)

    Kyong Nyon Nam; Jae-Hong Kim; Hoon-Ji Jung; Jung-Mi Park; Sang-Kwan Moon; Young-Suk Kim; Sun Yeou Kim; Eunjoo H.Lee

    2010-01-01

    Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors.Berberine,the effective ingredient of Coptidis Rhizoma and Cortex Phellodendri,has a wide range of pharmacological functions,including anti-inflammatory,anti-atherosclerotic and anti-cancer effects.The neuroprotective potential of berberine has previously been demonstrated.The present study aimed to examine whether berberine could repress microglial activation and can be considered a potential therapeutic candidate to target neurodegenerative diseases.Primary microglial cells and BV2 microglial cells were cultured and stimulated with bacterial lipopolysaccharide(LPS).Berberine chloride was treated prior to LPS or simultaneously with LPS stimulation.Results revealed that berberine was effective at inhibiting nitric oxide release from primary microglial cells when cells were exposed to the compound prior to LPS or simultaneously with LPS.It also reduced the LPS-stimulated production of tumor necrosis factor-α,interleukin-1β,prostaglandin E2,and intracellular reactive oxygen species and nuclear factor-kappa activation.Additionally,berberine reduced nitric oxide release from microglia stimulated with interferon-γ and amyloid β.These results suggest that berberine provides neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.

  9. Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

    Directory of Open Access Journals (Sweden)

    Patrik Htun

    Full Text Available Since patients with phenylketonuria (PKU have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT and ß-stiffness index] and platelet activation.In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation. CIMT was measured bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of CIMTleft and CIMTright.Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group.Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients.

  10. Relative risk for cardiovascular atherosclerotic events after smoking cessation: 6–9 years excess risk in individuals with familial hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Kastelein John JP

    2006-10-01

    Full Text Available Abstract Background Smoking history is often di- or trichotomized into for example "never, ever or current smoking". However, smoking must be treated as a time-dependent covariate when lifetime data is available. In particular, individuals do not smoke at birth, there is usually a wide variation with respect to smoking history, and smoking cessation must also be considered. Methods Therefore we analyzed smoking as a time-dependent risk factor for cardiovascular atherosclerotic events in a cohort of 2400 individuals with familial hypercholesterolemia who were followed from birth until 2004. Excess risk after smoking-cessation was modelled in a Cox regression model with linear and exponential decaying trends. The model with the highest likelihood value was used to estimate the decay of the excess risk of smoking. Results Atherosclerotic events were observed in 779 patients with familial hypercholesterolemia and 1569 individuals had a smoking history. In the model with the highest likelihood value the risk reduction of smoking after cessation follows a linear pattern with time and it appears to take 6 to 9 years before the excess risk is reduced to zero. The risk of atherosclerotic events due to smoking was estimated as 2.1 (95% confidence interval 1.5; 2.9. Conclusion It was concluded that excess risk due to smoking declined linearly after cessation in at least six to nine years.

  11. Inflammatory muscle diseases

    Directory of Open Access Journals (Sweden)

    Mastaglia F

    2008-01-01

    Full Text Available The three major immune-mediated inflammatory myopathies, dermatomyositis (DM, polymyositis (PM and inclusion body myositis (IBM, each have their own distinctive clinical features, underlying pathogenetic mechanisms and patterns of muscle gene expression. In DM a complement-dependent humoral process thought to be initiated by antibodies to endothelial cells results in a microangiopathy with secondary ischemic changes in muscles. On the other hand, in PM and IBM there is a T-cell response with invasion of muscle fibers by CD8+ lymphocytes and perforin-mediated cytotoxic necrosis. In IBM degenerative changes are also a feature and comprise autophagia with rimmed vacuole formation and inclusions containing β-amyloid and other proteins whose accumulation may be linked to impaired proteasomal function. The relationship between the inflammatory and degenerative component remains unclear, as does the basis for the selective vulnerability of certain muscles and the resistance to conventional forms of immunotherapy in most cases of IBM. Patients with DM or PM usually respond to treatment with glucocorticoids and immunosuppressive agents but their use remains largely empirical. Intravenous immunoglobulin therapy can be used to achieve disease control in patients with severe weakness or dysphagia, or in patients with immunodeficiency, but its use is limited by expense. Emerging therapies for resistant cases include TNFα inhibitors (etanercept, infliximab and monoclonal antibodies (rituximab, alemtuzumab. However, experience with these therapies is still limited and there is a need for randomized trials to test their efficacy and establish guidelines for their use in clinical practice.

  12. 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.

  13. Evaluation of atherosclerotic findings in patients with nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Mohammadi A

    2011-10-01

    Full Text Available Afshin Mohammadi1, Ali Bazazi2, Mohammad Ghasemi-rad21Department of Radiology, Urmia University of Medical Sciences, Urmia, West-Azerbaijan, Iran; 2Student Research Committee, Urmia University of Medical Sciences, Urmia, West-Azerbaijan, IranBackground: Nonalcoholic fatty liver disease (NAFLD, a highly prevalent condition, is a feature of metabolic syndrome and is characterized by excessive accumulation of fat in the liver cells. The purpose of this study was to investigate the association between NAFLD and carotid intima-media thickness (CIMT as an independent risk factor for atherosclerosis.Methods: We examined 250 consecutive patients with ultrasonographically confirmed NAFLD and 85 age-matched and gender-matched controls with normal parenchymal liver echogenicity for determination of CIMT and presence of carotid atherosclerotic plaque.Results: Compared with control subjects, patients with NAFLD showed an increased mean CIMT (0.81 ± 0.14 mm compared with control subjects (0.58 ± 0.15 mm. This difference was statistically significant (P = 0.001. After performing multivariate analysis, the presence of NAFLD was associated with abnormal CIMT independent of other atherogenic risk factors or its association with metabolic syndrome.Conclusion: NAFLD can be an independent risk factor for developing atherosclerosis. Therefore, NAFLD with and without metabolic syndrome can be associated with increased CIMT and increased risk of cardiovascular events in patients with NAFLD incidentally diagnosed on abdominal ultrasonography.Keywords: nonalcoholic fatty liver disease, metabolic syndrome, atherosclerosis, carotid intima media thickness, risk factor

  14. Safety and efficacy of coronary drug eluting stent for atherosclerotic stenosis of the small renal artery

    Institute of Scientific and Technical Information of China (English)

    LI Chun-jie; WU Zheng; YAN Hong-bing; WANG Jian; ZHAO Han-jun

    2009-01-01

    @@ Small diameter renal artery refers to the renal artery with the cross-section diameter less than 5 mm, the incidence of which is approximately 8%.1 Small diameter renal artery is common in patients with congenital multi-branch renal arteries, diabetes and multi-coronary artery lesions. Renal artery bare-mental stent (BMS) implantation is the standard treatment for ostial renal artery stenosis.2,3 However, the restenosis rate4-6 is too high and becomes one of the relative contraindications for small diameter renal artery stent implantation. Clinical trials (e.g. RAVEL,7,8 SIRIUS9 and TAXUS-IV10) have proved that drug eluting stent (DES), compared with BMS, can reduce the restenosis rate after the percutanous coronary intervention (PCI). And Huda et al11 claimed that DES had the better results than BMS in the treatment of obstructive superficial femoral artery disease. However,there are few studies involved restenosis after the renal artery intervention. We hypothesized that coronary DES applied in renal artery stenosis might inhibit intimal proliferation effectively as in coronary artery disease;therefore we evaluated the results of 25 patients with atherosclerotic renal artery stenosis treated using coronary DES to assess the safety and efficacy of coronary DES in patients with small renal artery stenotic lesions.

  15. Association of atherosclerotic renal artery stenosis with major adverse cardiovascular events after acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Zheng Bin; Liu Jinghua; Ma Qin; Zhao Donghui; Wang Xin; Zheng Ze

    2014-01-01

    Background Patients with atherosclerotic renal artery stenosis (ARAS) are in substantial risk of cardiovascular adverse events.We investigated whether myocardial infarction patients with ARAS are in additional risk of cardiovascular events.Methods In this retrospective study,257 patients with type 1 myocardial infarction were enrolled.Median follow-up was 42 months.Composite endpoint events are analyzed by definitions of ARAS as ≥50% or ≥70% diameter stenosis.Results Defining ARAS as ≥70% diameter stenosis,ARAS was a significant predictor for composite endpoint events including death,non-fatal myocardial infarction,ischaemic stroke and intracranial haemorrhage,rehospitalisation for cardiac failure (HR:4.381; 95% Cl:1.770-10.842) by Cox regression analysis,but not for death.Diabetes mellitus was also a significant predictor for composite endpoint events (HR:2.756; 95% Cl:1.295-5.863).However,defining ARAS ≥50% diameter stenosis,ARAS was no longer a significant predictor for composite endpoint events or death.Conclusions Although not associated with mortality,ARAS ≥70% is associated with major adverse cardiac events after acute myocardial infarction.For prognosis,≥70% diameter stenosis is a more appropriate criteria for ARAS definition than ≥50% diameter stenosis.

  16. Mechanical modeling of cholesterol crystallization in atherosclerotic plaques base on Micro-OCT images (Conference Presentation)

    Science.gov (United States)

    Luo, Yuemei; Liu, Xinyu; Chen, Si; Cui, Dongyao; Wang, Xianghong; Liu, Linbo

    2016-02-01

    Plaque rupture is the critical cause of cardiovascular thrombosis but this process is still under discussion. Recent studies show that, during crystallization, cholesterol crystals in atheromatous plaques accumulate rapidly in a limited space and may result in plaque rupture. However, the actual role of cholesterol crystals on plaque rupture remains unclear due to the lack of detailed morphological information of cholesterol crystals. In this study, we used a Micro-optical coherence tomography (µOCT) setup with 1-2 µm spatial resolution to extract the geometry of cholesterol crystals from human atherosclerotic artery ex vivo firstly. With measured dimensions of cholesterol crystals by this µOCT system (the average length and thickness of 269.1±80.16 µm and 3.0±0.33 µm), we developed a two-dimensional mechanical model in which rectangular shaped cholesterol crystals distribute at different locations spatially. We predicted the stress on the thin cap induced by the expansion of cholesterol crystals by use of finite-element method. Since a large portion of plaques (58%) rupture at points of peak circumferential stress (PCS), we used PCS as the primary indicator of plaque stability with blood pressure of 14.6 kPa on the lumen. The results demonstrate that loading of the concentrated crystals especially at the cap shoulder destabilize the plaque by proportionally increasing the PCS, while evenly distributed crystals loading along the cap might impose less PCS to the plaque than the concentrated case.

  17. Automatic classification of atherosclerotic plaques imaged with intravascular OCT (Conference Presentation)

    Science.gov (United States)

    Rico-Jimenez, Jose D.; Campos-Delgado, Daniel U.; Villiger, Martin; Bouma, Brett; Jo, Javier A.

    2016-03-01

    A novel computational method for plaque tissue characterization based on Intravascular Optical Coherence Tomography (IV-OCT) is presented. IV-OCT is becoming a powerful tool for the clinical evaluation of atherosclerotic plaques; however, it requires a trained expert for visual assessment and interpretation of the imaged plaques. Moreover, due to the inherit effect of speckle and the scattering attenuation of the optical scheme the direct interpretation of OCT images is limited. To overcome these difficulties, we propose to automatically identify the A-line profiles of the most significant plaque types (normal, fibrotic, or lipid-rich) and their respective abundance by using a probabilistic framework and blind alternated least squares to achieve the optimal decomposition. In this context, we present preliminary results of this novel probabilistic classification tool for intravascular OCT that relies on two steps. First, the B-scan is pre-processed to remove catheter artifacts, segment the lumen, select the region of interest (ROI), flatten the tissue surface, and reduce the speckle effect by a spatial entropy filter. Next, the resulting image is decomposed and its A-lines are classified by an automated strategy based on alternating-least-squares optimization. Our early results are encouraging and suggest that the proposed methodology can identify normal tissue, fibrotic and lipid-rich plaques from IV-OCT images.

  18. Postangioplasty Restenosis Followed with Magnetic Resonance Imaging in an Atherosclerotic Rabbit Model

    Directory of Open Access Journals (Sweden)

    Mari Hänni

    2012-01-01

    Full Text Available Rationale and Objectives. Testing a quantitative, noninvasive method to assess postangioplasty vessel wall changes in an animal model. Material and Methods. Six New Zealand white rabbits were subjected to atherosclerotic injury, including cholesterol-enriched diet, deendothelialization, and percutaneous transluminal angioplasty (PTA in the distal part of abdominal aorta (four weeks after deendothelialization. The animals were examined with a 1.5T MRI scanner at three times as follows: baseline (six weeks after diet start and two days after PTA and four weeks and 10 weeks after-PTA. Inflow angiosequence (M2DI and proton-density-weighted sequence (PDW were performed to examine the aorta with axial slices. To identify the inner and outer vessel wall boundaries, a dynamic contour algorithm (Gradient Vector Flow Snakes was applied to the images, followed by calculation of the vessel wall dimensions. The results were compared with histopathological analysis. Results. The wall thickness in the lesion was significantly higher than in the control region at 4 and 10 weeks, reflecting induction of experimentally created after-angioplasty lesion. At baseline, no significant difference between the two regions was present. Conclusions. It is possible to follow the development of vessel wall changes after-PTA with MRI in this rabbit model.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Platelet activation, function, and reactivity in atherosclerotic carotid artery stenosis: a systematic review of the literature.

    LENUS (Irish Health Repository)

    Kinsella, J A

    2012-09-27

    An important proportion of transient ischemic attack or ischemic stroke is attributable to moderate or severe (50-99%) atherosclerotic carotid stenosis or occlusion. Platelet biomarkers have the potential to improve our understanding of the pathogenesis of vascular events in this patient population. A detailed systematic review was performed to collate all available data on ex vivo platelet activation and platelet function\\/reactivity in patients with carotid stenosis. Two hundred thirteen potentially relevant articles were initially identified; 26 manuscripts met criteria for inclusion in this systematic review. There was no consistent evidence of clinically informative data from urinary or soluble blood markers of platelet activation in patients with symptomatic moderate or severe carotid stenosis who might be considered suitable for carotid intervention. Data from flow cytometry studies revealed evidence of excessive platelet activation in patients in the early, sub-acute, or late phases after transient ischemic attack or stroke in association with moderate or severe carotid stenosis and in asymptomatic moderate or severe carotid stenosis compared with controls. Furthermore, pilot data suggest that platelet activation may be increased in recently symptomatic than in asymptomatic severe carotid stenosis. Excessive platelet activation and platelet hyperreactivity may play a role in the pathogenesis of first or subsequent transient ischemic attack or stroke in patients with moderate or severe carotid stenosis. Larger longitudinal studies assessing platelet activation status with flow cytometry and platelet function\\/reactivity in symptomatic vs. asymptomatic carotid stenosis are warranted to improve our understanding of the mechanisms responsible for transient ischemic attack or stroke.

  1. Evaluation of the Effect of Andrographolide on Atherosclerotic Rabbits Induced by Porphyromonas gingivalis

    Directory of Open Access Journals (Sweden)

    Rami Al Batran

    2014-01-01

    Full Text Available Epidemiologic evidence has demonstrated significant associations between atherosclerosis and Porphyromonas gingivalis (Pg. We had investigated the effect of andrographolide (AND on atherosclerosis induced by Pg in rabbits. For experimental purpose, we separated thirty male white New Zealand rabbits into 5 groups. Group 1 received standard food pellets; Groups 2–5 were orally challenged with Pg; Group 3 received atorvastatin (AV, 5 mg/kg, and Groups 4-5 received 10 and 20 mg/kg of AND, respectively, over 12 weeks. Groups treated with AND showed significant decrease in TC, TG, and LDL levels (P<0.05 and significant increase in HDL level in the serum of rabbits. Furthermore, the treated groups (G3–G5 exhibited reductions in interleukins (IL-1β and IL-6 and C-reactive protein (CRP as compared to atherogenicgroup (G2. The histological results showed that the thickening of atherosclerotic plaques were less significant in treated groups (G3–G5 compared with atherogenicgroup (G2. Also, alpha-smooth muscle actin (α-SMA staining decreased within the plaques of atherogenicgroup (G2, while it was increased in treated groups (G3–G5. Lastly, groups treated with AV and AND (G3–G5 showed significant reduction of CD36 expression (P<0.05 compared to atherogenicgroup (G2. These results substantially proved that AND contain antiatherogenic activity.

  2. To Stent or Not to Stent? Update on Revascularization for Atherosclerotic Renovascular Disease.

    Science.gov (United States)

    Noory, Elias; Sritharan, Kaji; Zeller, Thomas

    2016-06-01

    Renal artery stenosis (RAS) is increasingly encountered in clinical practice. The two most common etiologies are fibromuscular dysplasia (FMD) and atherosclerotic renal artery disease (ARAS), with the latter accounting for the vast majority of cases. Significant RAS activates the renin-angiotensin-aldosterone system and is associated with three major clinical syndromes: ischemic nephropathy, hypertension, and destabilizing cardiac syndromes. Over the past two decades, advancements in diagnostic and interventional techniques have led to improved detection and the widespread use of endovascular renal artery revascularization strategies in the management of ARAS. However, renal artery stenting for ARAS remains controversial. Although several studies have demonstrated some benefit with renal artery revascularization, this has not been to the extent anticipated or predicted. Moreover, these trials have significant flaws in their study design and are hampered with inherent bias which make their interpretation challenging. In this review, we evaluate the existing body of evidence and offer an approach to the management of patients with ARAS in light of the current literature. From the data provided, identification of subgroup of patients, namely, those with a hemodynamically significant RAS in the context of progressive renal insufficiency and/or deteriorating arterial hypertension, seems possible and may derive clinical benefit from ARAS stent revascularization. Appropriate patient selection is therefore the key and more robust studies are required. PMID:27130448

  3. Sodium-Glucose Cotransporter 2 Inhibitors: Possible Anti-Atherosclerotic Effects Beyond Glucose Lowering.

    Science.gov (United States)

    Yanai, Hidekatsu; Katsuyama, Hisayuki; Hamasaki, Hidetaka; Adachi, Hiroki; Moriyama, Sumie; Yoshikawa, Reo; Sako, Akahito

    2016-01-01

    The new drug for type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, is reversible inhibitor of SGLT-2, leading to reduction of renal glucose reabsorption and decrease of plasma glucose, in an insulin-independent manner. In addition to glucose control, the management of coronary risk factors is very important for patients with diabetes. Here we reviewed published articles about the possible anti-atherosclerotic effects beyond glucose lowering of the SGLT-2 inhibitors. We searched by using Pubmed, and found 770 published articles about SGLT-2 inhibitors. Among 10 kinds of SGLT-2 inhibitors, the number of published articles about dapagliflozin was the greatest among SGLT-2 inhibitors. Since SGLT-2 inhibitors have similar chemical structures, we concentrated on the published articles about dapagliflozin. SGLT-2 inhibitors are proved to be significantly associated with weight loss and reduction of blood pressure by a relatively large number of studies. The studies investigating effects of dapagliflozin on visceral fat, insulin sensitivity, serum lipids, inflammation and adipocytokines are very limited. An influence of increase in glucagon secretion by SGLT-2 inhibitors on metabolic risk factors remains unknown. PMID:26668677

  4. Human macrophage scavenger receptors: Primary structure, expression, and localization in atherosclerotic lesions

    International Nuclear Information System (INIS)

    Two types of cDNAs for human macrophage scavenger receptors were cloned from a cDNA library derived from the phorbol ester-treated human monocytic cell line THP-1. The type I and type II human scavenger receptors encoded by these cDNAs are homologous (73% and 71% amino acid identity) to their previously characterized bovine counterparts and consist of six domains: cytoplasmic (I), membrane-spanning (II), spacer (III), α-helical coiled-coil (IV), collagen-like (V), and a type-specific C-terminal (VI). The receptor gene is located on human chromosome 8. The human receptors expressed in CHO-K1 cells mediated endocytosis of modified low density lipoproteins. Two mRNAs, 4.0 and 3.2 kilobases, have been detected in human liver, placenta, and brain. Immunohistochemical studies using an anti-peptide antibody which recognizes human scavenger receptors indicated the presence of the scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of scavenger receptors in atherogenesis

  5. Comparison between Adventitial and Intimal Inflammation of Ruptured and Nonruptured Atherosclerotic Plaques in Human Coronary Arteries

    Directory of Open Access Journals (Sweden)

    Higuchi Maria L.

    2002-01-01

    Full Text Available OBJECTIVE: To verify the possible role of adventitial inflammation in atherosclerotic plaque vulnerability and coronary artery remodelling. METHODS: We compared the mean numbers of lymphocytes in the adventitia and in the plaque of ruptured thrombosed and stable equi-stenotic coronary segments of 34 patients who died due to acute myocardial infarction. We also analysed adventitial microvessels, adventitial fibrosis and the external elastic membrane. RESULTS: In the adventitia, the numbers of lymphocytes and microvessels/mm² were 69.5±88.3 and 60.9± 32.1 in culprit lesions and 16.4 ± 21.1 and 44.3±16.1 in stable lesions (p<0.05; within the plaques, the mean number of lymphocytes was 24±40.8 in culprit lesions and 10.9±13.2 in stable ones (p=0.17. The mean percent area of adventitial fibrosis/cross-sectional area of the vessel was significantly lower in unstable plaques (p<0.001. The confocal images showed holes in the external elastic membrane. CONCLUSION: Unstable plaques exhibit chronic pan-arteritis, accompanied by enlargement, medial thinning, and less fibrosis than in stable lesions, which is compatible with vessel aneurysm. Adventitial inflammation may contribute significantly to atheroma instability.

  6. Inflammatory Bio marker Levels in Obese Prepubertal Children

    International Nuclear Information System (INIS)

    Childhood obesity has grown at an alarming rate, and is associated with metabolic disturbances that determine a higher risk of type 2 diabetes (T2DM) and atherosclerotic cardiovascular disease (CVD) in adulthood. These disturbances may arise at a very early age in obese children. These metabolic disturbances may be associated with insulin resistance (IR), a systemic low-grade inflammatory state and endothelial dysfunction. Thus it was aimed to determine the concentration levels of C-reactive protein (CRP), interleukin 6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) in obese pre-pubertal children, and their possible relation with metabolic syndrome. For this reason weight (kg), height (m), body mass index (BMI, kg/m2), systolic and diastolic blood pressure (SBP and DBP, mm Hg), fasting plasma glucose (FPG), lipid profile [total cholesterol (TC), cholesterol fractions HDL-C and LDL-C, and triglycerides (TGs)], fasting insulin (FI), fasting glucose ,HOMA-IR =fasting insulin (μU/ml) blood glucose (mg/dl)/405, CRP, IL-6 and sICAM-1 were analyzed in 30 obese and 15 non obese children. The results obtained displayed significantly elevated values for insulin (ρ= 0.001), homeostasis model assessment for IR (HOMA-IR, ρ 0.001), CRP (ρ< 0.001), IL-6 (ρ= 0.001) and sICAM-1 levels (ρ0.001) in obese children. Nonsignificant differences were found in fasting glucose. Moreover, sICAM- 1 showed a positive correlation with insulin, HOMA-IR, CRP and IL-6 (ρ= 0.042), (ρ= 0.0009), (ρ0.054) and (ρ= 0.026) respectively. It thus could be concluded that prepubertal obese children displayed alterations indicative of endothelial dysfunction, insulin resistance, and inflammatory state which may foreshadow an increased burden of CVD and T2DM in the future. Thus, early identification of the inflammatory and endothelial bio markers in obese children may assist in early interference to prevent progression and complications of type 2 DM and CVD. Moreover, longitudinal

  7. Efficient drug delivery to atherosclerotic lesions and the antiatherosclerotic effect by dexamethasone incorporated into liposomes in atherogenic mice.

    Science.gov (United States)

    Chono, Sumio; Tauchi, Yoshihiko; Deguchi, Yoshiharu; Morimoto, Kazuhiro

    2005-05-01

    In order to confirm the efficacy of dexamethasone (DXM) incorporated into liposomes (DXM-liposomes) on atherosclerosis, drug delivery to atherosclerotic lesions and the antiatherosclerotic effect by DXM-liposomes were investigated in atherogenic mice. DXM-liposomes were prepared with egg yolk phosphatidylcholine, cholesterol and dicetylphosphate in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to three different particle sizes to clarify the influence of particle size on the drug delivery to atherosclerotic lesions and the effect on atherosclerosis. The particle sizes of DXM-liposomes were 519 nm (L500), 202 nm (L200) and 68.6 nm (L70), respectively. In both size, DXM concentration and DXM/lipid molar ratio in DXM-liposomes suspension were 1 mg DXM/ml and 0.134 mol DXM/mol total lipids, respectively. Atherogenic mice used as an experimental model develop an atherosclerotic lesion in the aorta and they were prepared by feeding an atherogenic diet for 14 weeks. The aortic pharmacokinetics of DXM-liposomes was examined by intravenous administration to atherogenic mice. The aortic uptake clearance of DXM in atherogenic mice treated with L200 was 2.6--3.2 fold greater than that in animals treated with L500, L70 or free DXM (f-DXM). Furthermore, the effects of DXM-liposomes on atherosclerosis were examined by intravenous administration to atherogenic mice once a week from 8 to 14 weeks. The antiatherosclerotic effects of DXM-liposomes were evaluated by determination of the aortic cholesterol ester (CE) level. The aortic CE level in atherogenic mice treated with L200 (55 microg DXM/kg) was significantly lower than that in animals treated with PBS. The antiatherosclerotic effect of L200 (55 microg DXM/kg) was significantly more potent than that of f-DXM (550 microg DXM/kg). These findings suggest that efficient delivery of DXM to the atherosclerotic lesions by L200 induces an excellent antiatherosclerotic effect at a lower dose. Therefore, L200 may

  8. Evaluation of atherosclerotic lesions using dextran- and mannan–dextran-coated USPIO: MRI analysis and pathological findings

    Directory of Open Access Journals (Sweden)

    Mukaisho K

    2012-05-01

    Full Text Available Keiko Tsuchiya1, Norihisa Nitta1, Akinaga Sonoda1, Ayumi Nitta-Seko1, Shinichi Ohta1, Masashi Takahashi1, Kiyoshi Murata1, Kenichi Mukaisho2, Masashi Shiomi3, Yasuhiko Tabata4, Satoshi Nohara51Department of Radiology, 2Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, 3Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Hyogo, 4Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 5Nagoya Research Laboratory, Meito Sangyo, Kiyosu, Aichi, JapanAbstract: Magnetic resonance imaging (MRI can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic iron oxides (USPIO. Positing that improved USPIO with a higher affinity for atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of dextran- and mannan–dextran-coated USPIO (D-USPIO and DM-USPIO, respectively by the atherosclerotic walls of rabbits. We intravenously injected atherosclerotic rabbits with DM-USPIO (n = 5 or D-USPIO (n = 5. Two rabbits were the controls. The doses delivered were 0.08 (dose 1 (n = 1, 0.4 (dose 2 (n = 1, or 0.8 (dose 3 (n = 3 mmol iron/Kg. The dose 3 rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA before and 5 days after USPIO administration. Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR of the aortic wall in the same region of interest (ROI was calculated in both in vivo and in vitro studies. Histological assessment through measurement of iron-positive regions in Prussian blue-stained specimens showed that iron-positive regions were significantly larger in rabbits injected with DM- rather than D-USPIO (P < 0.05 for all doses. In vivo MRA showed that the SNR-reducing effect of DM- was greater than that of D-USPIO (P < 0.05. With in vitro MRI scans, SNR was significantly

  9. Inflammatory Bowel Disease and Thrombosis

    Directory of Open Access Journals (Sweden)

    Ahmet Tezel

    2012-06-01

    Full Text Available Inflammatory Bowel Disease (IBD is a group of chronic and relapsing inflammatory disorders of the gastrointestinal system. In these cases, findings are detected in extraintestinal systems also. There is a tendency for thrombotic events in IBD, as in the other inflammatory processes. The pathogenesis of this thrombotic tendency is multidimensional, including lack of natural anticoagulants, prothrombotic media induced via the inflammatory process, long-term sedentary life style, steroid use, surgery, and catheter placement. The aim of this review was to highlight the positive relationship between IBD and thrombotic events, and the proper treatment of at-risk patients.

  10. Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

    NARCIS (Netherlands)

    Rijnierse, Anneke

    2006-01-01

    The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex inter

  11. Inflammatory pathways of importance for management of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Pedersen, Jannie; Coskun, Mehmet; Soendergaard, Christoffer;

    2014-01-01

    Inflammatory bowel disease (IBD) is a group of chronic disorders of the gastrointestinal tract comprising Crohn's disease (CD) and ulcerative colitis (UC). Their etiologies are unknown, but they are characterised by an imbalanced production of pro-inflammatory mediators, e.g., tumor necrosis factor...

  12. Inflammatory bowel disease in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Dawn B Beaulieu; Sunanda Kane

    2011-01-01

    Crohn's disease and ulcerative colitis affect women in their child-bearing years. Family planning has come to be a common discussion between the gastroenterologist and the inflammatory bowel disease (IBD) patient.Disease control prior to desired conception and throughout pregnancy is the most important thing to keep in mind when caring for the IBD patient. Continued medical management during pregnancy is crucial in optimizing outcomes. Studies indicate that quiescent disease prior to conception infer the best pregnancy outcomes, similar to those in the general population.Active disease prior to and during pregnancy, can lead to complications such as pre-term labor, low birth weight, and small for gestational age infants. Although there are no definitive long term effects of pregnancy on IBD, there are some limited studies that suggest that it may alter the disease course. Understanding the literature and its limitations is important in the modern era of IBD care. Educating the patient and taking a team approach with the obstetrician will help achieve successful outcomes for mother and baby.

  13. Inflammatory and toxic myopathies.

    Science.gov (United States)

    Dalakas, M C

    1992-10-01

    The major advances in the immunopathogenesis and treatment of inflammatory myopathies, and the main criteria that distinguish polymyositis (PM) from dermatomyositis (DM) or inclusion-body myositis (IBM) are presented. The origin and implications of the amyloid and ubiquitin deposits found within the vacuolated fibers of patients with IBM are considered. The pathogenesis of human immunodeficiency virus (HIV) and human T-cell lymphotrophic virus (HTLV)-I-associated PM is presented, and the role of retroviruses in triggering PM, even in the absence of detectable viral genome within the muscle fibers, is discussed. In addition, three toxic myopathies with distinct morphologic, biochemical, or molecular characteristics, caused by zidovudine [azidothymidine (AZT) myopathy], the cholesterol-lowering-agent myopathy (CLAM), and the combination of blocking agents with corticosteroids are presented.

  14. [Chronic inflammatory demyelinating polyradiculoneuropathy].

    Science.gov (United States)

    Franques, J; Azulay, J-P; Pouget, J; Attarian, S

    2010-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating chronic neuropathy of immune origin whose diagnosis is based upon clinical, biological and electrophysiological data; previously critical to the diagnosis the nerve biopsy is now restricted to the rare situations where accurate diagnosis cannot be reached using these data alone. CIDP are mainly idiopathic, but a few associated diseases must be sought for as they require specific attention. Such associated diseases must particularly be discussed when the manifestations are severe or resistant to immunomodulating or immunosuppressive agents. Indeed, idiopathic CIDP are usually responsive to these treatments. The effectiveness of these treatments is limited by the importance of the secondary axonal loss. The dependence or the resistance may sometimes justify the association of several immunomodulating treatments. A single randomized controlled trial support the use of cytotoxic drugs and none with rituximab.

  15. Autoantibodies in inflammatory arthritis.

    Science.gov (United States)

    Conigliaro, P; Chimenti, M S; Triggianese, P; Sunzini, F; Novelli, L; Perricone, C; Perricone, R

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides. PMID:26970491

  16. Autoantibodies in inflammatory arthritis.

    Science.gov (United States)

    Conigliaro, P; Chimenti, M S; Triggianese, P; Sunzini, F; Novelli, L; Perricone, C; Perricone, R

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides.

  17. Chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Van den Bergh, Peter Y K; Rajabally, Yusuf A

    2013-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common autoimmune neuropathy. The diagnosis depends on the clinical presentation with a progressive or relapsing course over at least 2 months and electrophysiological evidence of primary demyelination. Whereas typical CIDP is quite easily recognizable because virtually no other neuropathies present with both distal and proximal motor and sensory deficit, atypical CIDP, focal and multifocal variants in particular, may represent a difficult diagnostic challenge. CIDP very likely is an underdiagnosed condition as suggested also by a positive correlation between prevalence rates and sensitivity of electrophysiological criteria. Since no 'gold standard' diagnostic marker exists, electrophysiological criteria have been optimized to be at the same time as sensitive and as specific as possible. Additional supportive laboratory features, such as increased spinal fluid protein, MRI abnormalities of nerve segments, and in selected cases nerve biopsy lead to the correct diagnosis in the large majority of the cases. Objective clinical improvement following immune therapy is also a useful parameter to confirm the diagnosis. The pathogenesis and pathophysiology of CIDP remain poorly understood, but the available evidence for an inflammatory origin is quite convincing. Steroids, intravenous immunoglobulin (IVIG), and plasma exchange (PE) have been proven to be effective treatments. IVIG usually leads to rapid improvement, which is useful in severely disabled patients. Repeat treatment over regular time intervals for many years is often necessary. The effect of steroids is slower and the side-effect profile may be problematic, but they may induce disease remission more frequently than IVIG. An important and as of yet uncompletely resolved issue is the evaluation of long-term outcome to determine whether the disease is still active and responsive to treatment.

  18. THE EFFECTS OF ANTI-INFLAMMATORY IFNγ AND PRO-INFLAMMATORY TNFα, IL-1β ON CHEMOKINE RELEASE IN MOUSE EPITHELIAL CELLS

    Science.gov (United States)

    RATIONALE: Asthma is a chronic inflammatory disorder of the airways that affects nearly 20 million individuals in the US. Airway inflammation is a hallmark characteristic of asthma and is the result of numerous pro-inflammatory cytokines such as IL-1β and TNFα . Interestingly...

  19. Anti-inflammatory management for tendon injuries - friends or foes?

    Directory of Open Access Journals (Sweden)

    Chan Kai-Ming

    2009-10-01

    Full Text Available Abstract Acute and chronic tendon injuries are very common among athletes and in sedentary population. Most physicians prescribe anti-inflammatory managements to relieve the worst symptoms of swelling and pain, including non-steroidal anti-inflammatory drugs, corticosteroids and physical therapies. However, experimental research shows that pro-inflammatory mediators such as prostaglandins may play important regulatory roles in tendon healing. Noticeably nearly all cases of chronic tendon injuries we treat as specialists have received non-steroidal anti-inflammatory drugs by their physician, suggesting that there might be a potential interaction in some of these cases turning a mild inflammatory tendon injury into chronic tendinopathy in predisposed individuals. We are aware of the fact that non-steroidal anti-inflammatory drugs and corticosteroids may well have a positive effect on the pain control in the clinical situation whilst negatively affect the structural healing. It follows that a comprehensive evaluation of anti-inflammatory management for tendon injuries is needed and any such data would have profound clinical and health economic importance.

  20. Vitamin D in inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Thea K Wöbke

    2014-07-01

    Full Text Available Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, atherosclerosis or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signalling modulates many inflammatory responses on several levels. This includes i the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, ii the interference with transcription factors, such as NF-kB, which regulate the expression of inflammatory genes and iii the activation of signalling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signalling and other signalling cascades involved in inflammation.An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP, ChIP-seq and FAIRE-seq.

  1. Immunohistochemical differentiation of inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Jayalakshmi B Panicker

    2011-01-01

    Full Text Available Background: Idiopathic inflammatory myopathies are a heterogeneous group of acquired muscle disorders with considerable overlap in the histological features, making histological diagnosis difficult at times. Aims: To determine the immunohistochemical profile of clinically suspected cases of inflammatory myopathies, using monoclonal antibodies to HLA-1 and membrane attack complex (MAC, and to correlate the clinical, serological, and electromyographic profile and the histopathological picture, with the immunohistochemical profile. Settings and Design: This was a retrospective study analyzing the clinical and histopathological features in muscle of clinically suspected cases of inflammatory myopathy and correlating it to their HLA-1 and MAC immunostaining profiles. Material and Methods: The study subjects included 33 cases with suspected inflammatory myopathy and 59 with non-inflammatory muscle disease, as controls. Clinical data, electromyographic findings, serological profile, and details of therapy were obtained from patient records. Statistical Analysis: Student ′T′ test, Pearson′s Chi square test, and Kappa statistics were used appropriately. Results: Although HLA-1 and MAC immunostaining did not help to differentiate the individual subtypes of inflammatory myopathy, when either HLA-1 or MAC was positive, inflammatory myopathy could be ruled in with 86.5% certainty and when both HLA-1 and MAC were negative, it could be ruled out with 95% certainty. Conclusions: A combination of clinical presentation, serological profile, electromyographic and histopathological features, together with the immunoprofile for HLA-1 and MAC, contribute toward making a diagnosis of inflammatory myopathy.

  2. Actions of Adjunctive Nutritional Antioxidants in Periodontitis and Prevalent Systemic Inflammatory Diseases.

    Science.gov (United States)

    El-Shinnawi, U; Soory, M

    2015-01-01

    Common risk markers for periodontitis and prevalent systemic comorbidities indicate similarities in their progression and molecular mechanisms involved. Resultant pro-oxidant disease profiles provide scope for attenuating their pathogeneses with appropriate adjunctive antioxidants. Levels of oxidative stress markers 8-hydroxy-deoxguanosine (8-HOdG) and malondialdehyde (MDA) are significantly higher in periodontitis and other chronic inflammatory conditions. There is a clear link between periodontitis and diseases associated with significant systemic inflammatory loading, such as metabolic syndrome. Micro- and macro-nutrients have proven to be effective in curbing molecular mechanisms that generate reactive oxygen and nitrogen species. A Mediterranean diet rich in fruits, vegetables, legumes, whole grain, nuts, fish, olive oil and red wine in moderation, could be attributed to the lower occurrence of cardiovascular disease, insulin resistance and other inflammatory diseases in this region. A significant number of naturally occurring flavonoids have been identified in these products. Flavonoids comprising flavonols, flavones and isoflavones are potent free radical scavengers, effective in inhibiting lipid peroxidation, with anti-atherosclerotic and antihypertensive effects.The phenolic compound oleocanthal isolated in virgin olive oil has similar anti-inflammatory actions to that of ibuprofen. The anti-atherogenic effects of MUFA and PUFA in nuts, enhance endothelial function by reducing total cholesterol, oxidized LDL, hs-CRP, sVCAM-1 levels, lipids, lipoproteins and inflammatory markers. Epigenetics influenced by environmental factors and interactions between genes and nutrients, are important considerations in influencing these effects. Using antioxidants as therapeutic adjuncts could enhance the antioxidant capacity of an inherent glutathione system and overcome oxidative effects, thereby mitigating therapeutic side-effects. PMID:25922082

  3. 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...

  4. Fistular onion stalk extract exhibits anti-atherosclerotic effects in rats

    Science.gov (United States)

    HE, BENHONG; HAO, JIANJUN; SHENG, WEIWEI; XIANG, YUANCAI; ZHANG, JIEMEIA; ZHU, HAO; TIAN, JINGCHENG; ZHU, XU; FENG, YUNXIA; XIA, HAO

    2014-01-01

    Fistular onion stalk is used as a traditional herbal medicine, and its extract exhibits certain beneficial effects on cardiovascular disease. In this study, the effects of fistular onion stalk extract on the pathological features, circulating inflammatory cytokines, local renin-angiotensin-aldosterone system (RAAS) and signaling pathway activities were examined using an in vivo model of atherosclerosis. Atherosclerosis of the aorta was induced by loading Sprague Dawley rats with a high-fat diet and vitamin D2. Fistular onion stalk extract administration began five weeks after the induction of atherosclerosis and continued for 12 weeks. Rats treated with fistular onion stalk extract showed a significant reduction in the pathological region compared with the vehicle-treated controls. Inhibition of atherosclerosis was associated with preservation of the vascular wall and immune cell infiltration. The extract also reduced the levels of the local inflammatory cytokines interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 and tumor necrosis factor-α. Furthermore, the extract downregulated the local activity of the RAAS. In addition, extract treatment inhibited several inflammatory signaling pathways by preventing phosphorylation, including the nuclear factor κB, Janus kinase/signal transducers and activators of transcription and mitogen-activated protein kinase pathways. These data indicate that fistular onion stalk extract may be useful for the attenuation of atherosclerosis, and the mechanism includes the regulation of the local inflammatory response. PMID:25120600

  5. Effects of Naoxintong on atherosclerosis and inducible nitric oxide synthase expression in atherosclerotic rabbit

    Institute of Scientific and Technical Information of China (English)

    ZHONG Xiao-nan; WANG Hong-hao; LU Zheng-qi; DAI Yong-qiang; HUANG Jian-hua; QIU Wei; SHU Ya-qing

    2013-01-01

    Background High levels of nitric oxide (NO) produced by inducible NO synthase (iNOS) have been associated with atherosclerosis processes.Naoxintong is a traditional Chinese medicine for treatment of cerebrovascular and cardiovascular disease.The aim of the present study was to detect and quantify changes of iNOS mRNA and NO levels in the vessel wall after the administration of Naoxintong in an atherosclerotic rabbit model.Methods Forty New Zealand white rabbits were randomly divided into five groups (n=8).Rabbits were fed a standard diet (group A),an atherogenic diet consisting of 79% standard feed+1% cholesterol+5% lard+15% egg yolk powder (group B),an atherogenic diet with Naoxintong 0.25 mg·kg-1·d-1 (group C),an atherogenic diet with Naoxintong 0.5mg·kg-1·d-1 (group D),or atherogenic diet with Naoxintong 1.0 mg·kg-1·d-1 (group E) for 12 weeks.Results Supplemented administration of Naoxintong led to a down-regulation of cholesterol (CHOL) (P <0.001) and low-density lipoprotein (LDL) (P <0.001).The trend became more notable as the dose of Naoxintong increased; group Cvs.group B (CHOL,P=0.568; LDL-cholesterol (LDL-C),P=0.119),group D vs.group B (CHOL,P=0.264; LDL-C,P=0.027),group E vs.group B (CHOL,P=0.028; LDL-C,P=0.002).Atherosclerotic lesions in aorta were reduced in Naoxintong groups (groups C,D,E) compared to group B.Group B had higher iNOS mRNA (P=0.001) and NO level (P<0.001) than group A.Compared with the atherogenic diet fed-rabbits,Naoxintong supplements decreased the expression of iNOS mRNA (P <0.001) and the NO level (P <0.001) in the vessel wall.Groups given a higher Naoxintong dose exhibited greater benefits.iNOS mRNA and NO levels seemed to be reduced in group C,although the difference did not quite reach statistical significance (iNOS mRNA,P=0.130; NO,P=0.038).iNOS mRNA and NO levels significantly decreased in group D (iNOS mRNA,P=0.019; NO,P=0.018) and group E (iNOS mRNA,P=0.004; NO,P<0.001).Conclusion Naoxintong has

  6. Functional and anatomical measures for outflow boundary conditions in atherosclerotic coronary bifurcations.

    Science.gov (United States)

    Schrauwen, Jelle T C; Coenen, Adriaan; Kurata, Akira; Wentzel, Jolanda J; van der Steen, Antonius F W; Nieman, Koen; Gijsen, Frank J H

    2016-07-26

    The aim of this research was finding the influence of anatomy-based and functional-based outflow boundary conditions for computational fluid dynamics (CFD) on fractional flow reserve (FFR) and wall shear stress (WSS) in mildly diseased coronary bifurcations. For 10 patient-specific bifurcations three simulations were set up with different outflow conditions, while the inflow was kept constant. First, the outflow conditions were based on the diameter of the outlets. Second, they were based on the volume estimates of the myocardium that depended on the outlets. Third, they were based on a myocardial flow measure derived from computed tomography perfusion imaging (CTP). The difference in outflow ratio between the perfusion-based and the diameter-based approach was -7 p.p. [-14 p.p.:7 p.p.] (median percentage point and interquartiles), and between the perfusion-based and volume-based this was -2 p.p. [-2 p.p.:1 p.p.]. Despite of these differences the computed FFRs matched very well. A quantitative analysis of the WSS results showed very high correlations between the methods with an r(2) ranging from 0.90 to 1.00. But despite the high correlations the diameter-based and volume-based approach generally underestimated the WSS compared to the perfusion-based approach. These differences disappeared after normalization. We demonstrated the potential of CTP for setting patient-specific boundary conditions for atherosclerotic coronary bifurcations. FFR and normalized WSS were unaffected by the variations in outflow ratios. In order to compute absolute WSS a functional measure to set the outflow ratio might be of added value in this type of vessels.

  7. Morphometric and hemodynamic analysis of atherosclerotic progression in human carotid artery bifurcations.

    Science.gov (United States)

    Huang, Xu; Yin, Xiaoping; Xu, Yingjin; Jia, Xinwei; Li, Jianhui; Niu, Pei; Shen, Wenzeng; Kassab, Ghassan S; Tan, Wenchang; Huo, Yunlong

    2016-03-01

    Although atherosclerosis has been widely investigated at carotid artery bifurcation, there is a lack of morphometric and hemodynamic data at different stages of the disease. The purpose of this study was to determine the lesion difference in patients with carotid artery disease compared with healthy control subjects. The three-dimensional (3D) geometry of carotid artery bifurcation was reconstructed from computed tomography angiography (CTA) images of Chinese control subjects (n = 30) and patients with carotid artery disease (n = 30). We defined two novel vector angles (i.e., angles 1 and 2) that were tangential to the reconstructed contour of the 3D vessel. The best-fit diameter was computed along the internal carotid artery (ICA) center line. Hemodynamic analysis was performed at various bifurcations. Patients with stenotic vessels have larger angles 1 and 2 (151 ± 11° and 42 ± 20°) and smaller diameters of the external carotid artery (ECA) (4.6 ± 0.85 mm) compared with control subjects (144 ± 13° and 36 ± 16°, 5.2 ± 0.57 mm) although there is no significant difference in the common carotid artery (CCA) (7.1 ± 1.2 vs. 7.5 ± 1.0 mm, P = 0.18). In particular, all patients with carotid artery disease have a stenosis at the proximal ICA (including both sinus and carina regions), while 20% of patients have stenosis at the middle ICA and 20% have stenosis expansion to the entire cervical ICA. Morphometric and hemodynamic analyses suggest that atherosclerotic plaques initiate at both sinus and carina regions of ICA and progress downstream.

  8. Association of carotid atherosclerotic plaque features with acute ischemic stroke: A magnetic resonance imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Huilin [Department of Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Zhao, Xihai [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing 100084 (China); Liu, Xiaosheng; Cao, Ye [Department of Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Hippe, Daniel S.; Sun, Jie [Department of Radiology, University of Washington, Seattle, WA 98109 (United States); Li, Feiyu [Department of Radiology, Peking University First Hospital, Beijing 100034 (China); Xu, Jianrong, E-mail: renjixjr@yahoo.com.cn [Department of Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Yuan, Chun [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing 100084 (China); Department of Radiology, University of Washington, Seattle, WA 98109 (United States)

    2013-09-15

    Background and purpose: It remains unclear whether direct vessel wall imaging can identify carotid high-risk lesions in symptomatic subjects and whether carotid plaque characteristics are more effective indicators for cerebral infarct severity than stenosis. This study sought to determine the associations of carotid plaque characteristics by MR imaging with stenosis and acute cerebral infarct (ACI) sizes on diffusion weighted imaging (DWI). Materials and methods: One hundred and fourteen symptomatic patients underwent carotid and brain MRI. ACI volume was determined from symptomatic internal carotid artery territory on DWI images. Ipsilateral carotid plaque morphological and compositional characteristics, and stenosis were also determined. The relationships between carotid plaque characteristics, stenosis and ACIs size were then evaluated. Results: In carotid arteries with 30–49% stenosis, 86.7% and 26.7% were found to have lipid-rich necrotic core (LRNC) and intraplaque hemorrhage, respectively. Furthermore, 45.8% of carotid arteries with 0–29% stenosis developed LRNCs. Carotid morphological measurements, such as % wall volume, and the LRNC size were significantly associated with ipsilateral ACIs volume before and after adjustment for significant demographic factors (age and LDL) or stenosis in patients with carotid plaque (all p < 0.05). Conclusions: A substantial number of high-risk plaques characterized by vessel wall imaging exist in carotid arteries with lower grade stenosis. In addition, carotid plaque characteristics, particularly the % wall volume and LRNC size, are independently associated with cerebral infarction as measured by DWI lesions. Our findings indicate that characterizing atherosclerotic plaque by MR vessel wall imaging might be useful for stratification of plaque risk and infarction severity.

  9. Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

    Directory of Open Access Journals (Sweden)

    Ning Ma

    Full Text Available OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5% with acute thrombosis, 5 patients (1.8% with subacute thrombosis, 17 patients (6.2% with stroke, and 2 death (0.7% in low-dose aspirin group, compared with no patient (0% with acute thrombosis, 2 patient (2.1% with subacute thrombosis, 6 patients (6.2% with stroke, and 2 death (2.1% in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

  10. Knowledge of modifiable risk factors of Coronary Atherosclerotic Heart Disease (CASHD among a sample in India

    Directory of Open Access Journals (Sweden)

    Ku Melvin

    2009-02-01

    Full Text Available Abstract Background The prevalence of Coronary Atherosclerotic Heart Disease (CASHD is increasing in India. Several modifiable risk factors contribute directly to this disease burden. Public knowledge of such risk factors among the urban Indian population is largely unknown. This investigation attempts to quantify knowledge of modifiable risk factors of CASHD as sampled among an Indian population at a large metropolitan hospital. Methods A hospital-based, cross sectional study was conducted at All India Institute of Medical Sciences (AIIMS, a major tertiary care hospital in New Delhi, India. Participants (n = 217 recruited from patient waiting areas in the emergency room were provided with standardized questionnaires to assess their knowledge of modifiable risk factors of CASHD. The risk factors specifically included smoking, hypertension, elevated cholesterol levels, diabetes mellitus and obesity. Identifying 3 or less risk factors was regarded as a poor knowledge level, whereas identifying 4 or more risk factors was regarded as a good knowledge level. A multiple logistic regression model was used to isolate independent demographic markers predictive of a participant's level of knowledge. Results 41% of the sample surveyed had a good level of knowledge. 68%, 72%, 73% and 57% of the population identified smoking, obesity, hypertension, and high cholesterol correctly, respectively. 30% identified diabetes mellitus as a modifiable risk factor of CASHD. In multiple logistic regression analysis independent demographic predictors of a good knowledge level with a statistically significant (p Conclusion An Indian population in a hospital setting shows a lack of knowledge pertaining to modifiable risk factors of CASHD. By isolating demographic predictors of poor knowledge, such as current smokers and persons who do not exercise regularly, educational interventions can be effectively targeted and implemented as primary and secondary prevention strategies

  11. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology.

    Science.gov (United States)

    Nordestgaard, Børge G

    2016-02-19

    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 to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5.1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate 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-cause mortality. PMID:26892957

  12. Association between self-reported oral health, tooth loss and atherosclerotic burden

    Directory of Open Access Journals (Sweden)

    Maximiliano Schünke Gomes

    2012-10-01

    Full Text Available Previous studies have suggested that oral diseases may influence the development of atherosclerosis. The aim of this study was to test the hypothesis that poor self-reported oral health (SROH and tooth loss are positively associated with coronary atherosclerotic burden (CAB. 382 consecutive subjects undergoing coronary angiography were included. Socio-demographic characteristics, cardiovascular risk factors and oral health status were collected using a standardized questionnaire, including data on SROH and use of dental prosthesis. Number of teeth and anthropometric measures were collected through clinical examinations. CAB at coronary angiography was quantified using the Friesinger score (FS. Prevalence ratios (PR were calculated with Poisson regression analyses. Mean age was 60.3 ± 10.8 years, with 63.2% males. In the bivariate analysis, there was a significant association (p 60y (PR = 1.01, 95%CI = 1.02-1.16, male gender (PR = 1.11, 95%CI = 1.03-1.19, smoking (PR = 1.08, 95%CI = 1.01- 1.16, hypertension (PR = 1.12, 95%CI = 1.03-1.22, diabetes (PR = 1.17, 95%CI = 1.05-1.21, poor SROH (PR = 1.22, 95%CI = 1.02-1.46 and tooth loss (< 20teeth present (PR = 1.10, 95%CI = 1.02-1.19. The use of dental prosthesis was not associated with CAB. The multivariate models, adjusted for age, gender, smoking, hypertension, diabetes and dyslipidemia showed that poor SROH (p = 0.03 and tooth loss (p = 0.02 were independently associated with CAB, confirming the study hypothesis.

  13. Support vector machine based classification and mapping of atherosclerotic plaques using fluorescence lifetime imaging (Conference Presentation)

    Science.gov (United States)

    Fatakdawala, Hussain; Gorpas, Dimitris S.; Bec, Julien; Ma, Dinglong M.; Yankelevich, Diego R.; Bishop, John W.; Marcu, Laura

    2016-02-01

    The progression of atherosclerosis in coronary vessels involves distinct pathological changes in the vessel wall. These changes manifest in the formation of a variety of plaque sub-types. The ability to detect and distinguish these plaques, especially thin-cap fibroatheromas (TCFA) may be relevant for guiding percutaneous coronary intervention as well as investigating new therapeutics. In this work we demonstrate the ability of fluorescence lifetime imaging (FLIm) derived parameters (lifetime values from sub-bands 390/40 nm, 452/45 nm and 542/50 nm respectively) for generating classification maps for identifying eight different atherosclerotic plaque sub-types in ex vivo human coronary vessels. The classification was performed using a support vector machine based classifier that was built from data gathered from sixteen coronary vessels in a previous study. This classifier was validated in the current study using an independent set of FLIm data acquired from four additional coronary vessels with a new rotational FLIm system. Classification maps were compared to co-registered histological data. Results show that the classification maps allow identification of the eight different plaque sub-types despite the fact that new data was gathered with a different FLIm system. Regions with diffuse intimal thickening (n=10), fibrotic tissue (n=2) and thick-cap fibroatheroma (n=1) were correctly identified on the classification map. The ability to identify different plaque types using FLIm data alone may serve as a powerful clinical and research tool for studying atherosclerosis in animal models as well as in humans.

  14. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    . Under these circumstances affective aesthetics operate strategically within the urban field of interests, capital flows and desires of the social. This ‘affective urbanism’ (Anderson & Holden 2008) is linked to a society influenced by new kinds of information flows, where culture is mediated and enacted...... and cultural festivals, both practices indicate that design is implemented as means of creating affective spaces in the city. Both cases show how immaterial production of affects and emotions in the city can be seen in relation to economic potential and urban development. Finally, I will discuss whether urban......Urban design and architecture are increasingly used as material and affective strategies for setting the scene, for manipulation and the production of urban life: The orchestration of atmospheres, the framing and staging of urban actions, the programming for contemplation, involvement, play...

  15. Ablation of adenosine monophosphate-activated protein kinaseα1 in vascular smooth muscle cells promotes diet-induced atherosclerotic calcification in vivo

    Institute of Scientific and Technical Information of China (English)

    CAI Zhe-jun; DING Ye; ZHANG Miao; LU Qiu-lun; WU Sheng-nan; ZHU Huai-ping; SONG Ping; ZOU Ming-hui

    2016-01-01

    AIM:Atherosclerotic calcification is highly linked with plaque instability and cardiovascular events .Adenosine monophosphate-activated protein kinase ( AMPK) has been involved in the pathogenesis of various cardiovascular disease .The contributions of AMPKαsubunits to the development of atherosclerotic calcification in vivo remained unknown .We hypothesized that AMPKαsubunits may play a role in the development of atherosclerotic calcification .METHODS: Atherosclerotic calcification was generated by 24-week fed of western diet in ApoE-/-background mice .Calcification was evaluated in aortic roots and innominate arteries of ApoE-/-mice or in mice with dual deficiencies of ApoE and AMPKαsubunits globally ( AMPKα1 and AMPKα2 ) , or vascular smooth muscle cell ( VSMC)-specific or macrophage-specific knockout of AMPKα1 with atherosclerotic calcification pone diet . The mechanism of AMPKα1 in regulating Runx2 was further explored in human aortic VSMC .RESULTS: Ablation of AMPKα1 but not AMPKα2 in ApoE-/-background promoted atherosclerotic calcification with increased Runt -related transcription factor ( Runx2 ) expression in VSMC compared with ApoE-/-mice.Conversely, chronic administration of metformin, which activated AMPK, markedly reduced ath-erosclerotic calcification and Runx2 expression in ApoE-/-mice but had less effects in ApoE-/-/AMPKα1 -/-mice.Furthermore, VSMC-but not macrophage-specific deficiency of AMPKα1 in ApoE-/-background promoted atherosclerotic calcification in vivo com-pared with the controls .AMPKα1 silencing in human aortic VSMC prevented Runx 2 from proteasome degradation to trigger osteoblastic differentiation of VSMC .Conversely , activation of AMPK led to Runx 2 instability by inducing its small ubiquitin-like modifier modifi-cation (SUMOylation).Protein inhibitor of activated STAT-1 (PIAS1), the SUMO E3-ligase of Runx2, was directly phosphorylated by AMPKα1 at serine 510, to enhance its SUMO E3-ligase activity.Ablation of PIAS1

  16. Inflammatory and oxidative stress in rotavirus infection

    Science.gov (United States)

    Guerrero, Carlos A; Acosta, Orlando

    2016-01-01

    Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum (ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species (ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virus-associated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines. PMID:27175349

  17. THE EFFECTS OF COMBINATORIAL EXPOSURE OF PRO-INFLAMMATORY AND ANTI-INFLAMMATORY CYTOKINES ON AIRWAY EPITHELIAL CELL RELEASE OF CHEMOTACTIC MEDIATORS

    Science.gov (United States)

    Asthma is a chronic inflammatory disorder of the airways affecting nearly 15 million individuals nationally. Within the inflamed asthmatic airway there exist complex interactions between many cells and the cytokines they release, in particular mast cells, eosinophils, T-lymphocy...

  18. Erdosteine: antitussive and anti-inflammatory effects.

    Science.gov (United States)

    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  19. Erdosteine: antitussive and anti-inflammatory effects.

    Science.gov (United States)

    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  20. Lipid volume fraction in atherosclerotic plaque phantoms classified under saline conditions by multispectral angioscopy at near-infrared wavelengths around 1200 nm.

    Science.gov (United States)

    Matsui, Daichi; Ishii, Katsunori; Awazu, Kunio

    2016-05-01

    To identify high-risk atherosclerotic lesions, we require detailed information on the stability of atherosclerotic plaques. In this study, we quantitatively classified the lipid volume fractions in atherosclerotic plaque phantoms by a novel angioscope combined with near-infrared multispectral imaging. The multispectral angioscope was operated at peak absorption wavelengths of lipid in vulnerable plaques (1150, 1200, and 1300 nm) and at lower absorption wavelengths of water. The potential of the multispectral angioscope was demonstrated in atherosclerotic plaque phantoms containing 10-60 vol.% lipid and immersed in saline solution. The acquired multispectral data were processed by a spectral angle mapper algorithm, which enhanced the simulated plaque areas. Consequently, we classified the lipid volume fractions into five categories (0-5, 5-15, 15-30, 30-50, and 50-60 vol.%). Multispectral angioscopy at wavelengths around 1200 nm is a powerful tool for quantitatively evaluating the stability of atherosclerotic plaques based on the lipid volume fractions. PMID:26861978