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  1. Electrochemical Impedance Spectroscopy to Characterize Inflammatory Atherosclerotic Plaques

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    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. 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.

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

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

    2009-01-15

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

  4. 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.

  5. Lactobacillus acidophilus ATCC 4356 attenuates the atherosclerotic progression through modulation of oxidative stress and inflammatory process.

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    Chen, Lihua; Liu, Wenen; Li, Yanming; Luo, San; Liu, Qingxia; Zhong, Yiming; Jian, Zijuan; Bao, Meihua

    2013-09-01

    The aim of this study was to investigate the effect of Lactobacillus (L.) acidophilus ATCC 4356 on the progression of atherosclerosis in Apoliprotein-E knockout (ApoE(-/-)) mice and the underlying mechanisms. Eight week-old ApoE(-/-) mice were treated with L. acidophilus ATCC 4356 daily for 12 weeks. The wild type (WT) mice or ApoE(-/-) mice in the vehicle group were treated with saline only. Body weights, serum lipid levels, aortic atherosclerotic lesions, and tissue oxidative and inflammatory statuses were examined among the groups. As compared to ApoE(-/-) mice in the vehicle group, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 had no changes in body weights and serum lipid profiles, but showed decreased atherosclerotic lesion size in en face aorta. In comparison with WT mice, ApoE(-/-) mice in the vehicle group showed higher levels of serum malondialdehyde (MDA), oxidized low density lipoprotein (oxLDL) and tumor necrosis factor-alpha (TNF-α), but lower levels of interleukin-10 (IL-10) and superoxide dismutase (SOD) activities in serum. Administration of L. acidophilus ATCC 4356 could reverse these trends in a dose-dependent manner in ApoE(-/-) mice. Furthermore, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 showed an inhibition of translocation of NF-κB p65 from cytoplasm to nucleus, suppression of degradation of aortic IκB-α, and improvements of gut microbiota distribution, as compared to ApoE(-/-) mice in the vehicle group. Our findings suggest that administration of L. acidophilus ATCC 4356 can attenuate the development of atherosclerotic lesions in ApoE(-/-) mice through reducing oxidative stress and inflammatory response.

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

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    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

  7. 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.

  8. 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.

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

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    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.

  10. Iron-oxide-enhanced MR imaging of inflammatory atherosclerotic lesions: overview of experimental and initial clinical results; Eisenoxidverstaerkte MRT inflammatorischer atherosklerotischer Laesionen: Uebersicht experimenteller und erster klinischer Ergebnisse

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    Schmitz, S.A. [Klinik und Poliklinik fuer Radiologie und Nuklearmedizin, Universitaetsklinikum Benjamin Franklin, Berlin (Germany)

    2003-04-01

    Numerous pathologic studies in the 1990's have shown atherosclerosis to be a chronic inflammatory disorder. This new insight and the advent of new plaque-stabilizing drugs, in particular antilipemic agents (statins), have led to an increased clinical interest in the development of new imaging modalities. These are aimed at visualizing the inflammatory atherosclerotic wall lesion as reflecting the active progression of the disease process and at identifying so-called vulnerable or high-risk lesions that are associated with a higher rate of vascular complications. A diagnostic modality currently undergoing investigation in terms of its potential for the diagnostic assessment of atherosclerosis is contrast-enhanced magnetic resonance imaging (MRI) using certain blood pool contrast media such as ultrasmall superparamagnetic iron oxide (USPIO) particles. Endothelial dysfunction and macrophage infiltration are two crucial pathomechanisms of atherosclerosis and these mechanisms also underlie the accumulation of iron oxide particles in experimental and human atherosclerotic lesions. Experimental results furthermore suggest that there is selective uptake of iron oxide by thrombi. The following experimental MR imaging techniques have a potential for providing complementary diagnostic information in assessing atherosclerotic lesions: 1. Unenhanced MRI for visualizing vulnerable plaques (wall thickness, fibrous cap, lipid core). 2. Visualization of the vessel lumen and quantitative assessment of stenosis using iron-oxide-enhanced MR angiography. 3. Delayed MRI studies for the functional characterization of inflammatory lesions (T{sub 2}-effects produced by iron oxide uptake in macrophages of inflammatory lesions) with a potential for identifying mural thrombus as a sign of plaque rupture (T{sub 1}-effects produced by binding of iron oxide to the thrombus). This article presents the experimental and initial clinical results obtained with iron-oxide-enhanced MRI of

  11. 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

  12. 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.

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

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    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.

  14. 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.

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

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    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.

  16. 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.

  17. 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.

  18. 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.

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    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.

  19. Mathematical models for atherosclerotic plaque evolution

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    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

  20. Sleep deprivation affects inflammatory marker expression in adipose tissue

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    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.

  1. Probiotic yogurt Affects Pro- and Anti-inflammatory Factors in Patients with Inflammatory Bowel Disease.

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    Shadnoush, Mahdi; Shaker Hosseini, Rahebeh; Mehrabi, Yadollah; Delpisheh, Ali; Alipoor, Elham; Faghfoori, Zeinab; Mohammadpour, Nakisa; Zaringhalam Moghadam, Jalal

    2013-01-01

    Inflammatory bowel disease (IBD) is an irregular response of immune system accompanied with different inflammatory manifestations including alterations in cytokines. Probiotics are non-pathogenic organisms with probable effects in various conditions such as inflammation. The present study hypothesized whether oral intake of bifidobacterium and lactobacillus in form of probiotic yogurt may represent an immunomodulatory effect in IBD patients. Overally, 210 patients in remission phase and 95 healthy people were recruited. Patients were randomly divided into two groups of either 250 grams of probiotic yogurt (PI) or 250 grams of plain yogurt (PC) daily for 8 weeks. The healthy control group (HG) also received probiotic yogurt as noted. The serum levels of cytokines TNF-α, IL-6, IL-1β, IL-10 and CRP levels were measured at baseline and at termination time. A significant difference was observed between intervention groups of PI and PC with HG group (p probiotics.

  2. Environmental factors affecting inflammatory bowel disease: have we made progress?

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    Lakatos, Peter Laszlo

    2009-01-01

    The pathogenesis of inflammatory bowel disease (IBD) is only partially understood; various environmental and host (e.g. genetic, epithelial, immune, and nonimmune) factors are involved. The critical role for environmental factors is strongly supported by recent worldwide trends in IBD epidemiology. One important environmental factor is smoking. A meta-analysis partially confirms previous findings that smoking was found to be protective against ulcerative colitis and, after the onset of the disease, might improve its course, decreasing the need for colectomy. In contrast, smoking increases the risk of developing Crohn's disease and aggravates its course. The history of IBD is dotted by cyclic reports on the isolation of specific infectious agents responsible for Crohn's disease or ulcerative colitis. The more recently published cold chain hypothesis is providing an even broader platform by linking dietary factors and microbial agents. An additional, recent theory has suggested a breakdown in the balance between putative species of 'protective' versus 'harmful' intestinal bacteria - this concept has been termed dysbiosis resulting in decreased bacterial diversity. Other factors such as oral contraceptive use, appendectomy, dietary factors (e.g. refined sugar, fat, and fast food), perinatal events, and childhood infections have also been associated with both diseases, but their role is more controversial. Nonetheless, there is no doubt that economic development, leading to improved hygiene and other changes in lifestyle ('westernized lifestyle') may play a role in the increase in IBD. This review article focuses on the role of environmental factors in the pathogenesis and progression of IBDs.

  3. 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

  4. 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.

  5. Study of the evolution of aortic atherosclerotic inflammatory plaques using {sup 18}F-FDG PET/CT; Evolution temporelle des foyers inflammatoires d'atherome aortique avec le morphoTEP au {sup 18}F-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Bertrand, A.C.; Netter, F.; Muller, M.A.; Djaballah, W.; Bruna, C.; Olivier, P.; Karcher, G.; Marie, P.Y. [Centre Hospitalier Universitaire, Service de Medecine Nucleaire, 54 - Nancy (France)

    2006-02-15

    PET allows focal uptake of {sup 18}F-FDG to be identified on aortic walls, and these foci might be linked to inflammatory atherosclerotic plaques. The goal of our study was to determine the temporal evolution of these foci. Material and methods: Twenty eight patients undergoing two {sup 18}F-FDG PET/CT within a two month period (1.5{+-}0.5 months on average), were considered. {sup 18}F-FDG uptakes were visually detected on thoracic aorta walls and the maximum activity level of these foci was expressed by a ratio with blood aortic activity (W/B). Results: 35 parietal aortic foci were detected on the initial PET/CT among which 26 were still detected on the second PET/CT together with 5 new foci; therefore the agreement rate between the two examinations was 65% for the visual detection of parietal aortic foci. The ratio W/B was 1.48{+-}0.22 on average. Between the two examinations the evolution of the W/B ratio was only correlated to the initial activity (p=0.02), mainly because the most active foci (W/B>1.6) had a marked activity decrease. Conclusion: When 2 different PET/CT are carried out on the same patients within lower than a two month period, activity from parietal aortic foci seems generally stable, with a concordance rate of 65% between the 2 investigations, and this might relate to a chronic mode of the evolution of inflammation and atherosclerosis. A further decrease in activity was, however, consistently documented for the foci showing the highest activity at baseline, and this might relate to a more evolutive and acute inflammatory process. (author)

  6. Arterial luminal curvature and fibrous-cap thickness affect critical stress conditions within atherosclerotic plaque: an in vivo MRI-based 2D finite-element study.

    Science.gov (United States)

    Teng, Zhongzhao; Sadat, Umar; Li, Zhiyong; Huang, Xueying; Zhu, Chengcheng; Young, Victoria E; Graves, Martin J; Gillard, Jonathan H

    2010-10-01

    High mechanical stress in atherosclerotic plaques at vulnerable sites, called critical stress, contributes to plaque rupture. The site of minimum fibrous cap (FC) thickness (FC(MIN)) and plaque shoulder are well-documented vulnerable sites. The inherent weakness of the FC material at the thinnest point increases the stress, making it vulnerable, and it is the big curvature of the lumen contour over FC which may result in increased plaque stress. We aimed to assess critical stresses at FC(MIN) and the maximum lumen curvature over FC (LC(MAX)) and quantify the difference to see which vulnerable site had the highest critical stress and was, therefore, at highest risk of rupture. One hundred patients underwent high resolution carotid magnetic resonance (MR) imaging. We used 352 MR slices with delineated atherosclerotic components for the simulation study. Stresses at all the integral nodes along the lumen surface were calculated using the finite-element method. FC(MIN) and LC(MAX) were identified, and critical stresses at these sites were assessed and compared. Critical stress at FC(MIN) was significantly lower than that at LC(MAX) (median: 121.55 kPa; inter quartile range (IQR) = [60.70-180.32] kPa vs. 150.80 kPa; IQR = [91.39-235.75] kPa, p LC(MAX) only was used, then 112 out of 352 would be underestimated. Stress analysis at FC(MIN) and LC(MAX) should be used for a refined mechanical risk assessment of atherosclerotic plaques, since material failure at either site may result in rupture.

  7. 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...... and a decrease in adiponectin. TEMPOL supplementation reversed these effects. When compared to HFD-fed mice, TEMPOL supplementation increased plaque collagen content, decreased lipid content and increased macrophage numbers. CONCLUSIONS: These data indicate that in a well-established model of obesity...

  8. Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells

    NARCIS (Netherlands)

    M.J. Crop (Meindert); C.C. Baan (Carla); S.S. Korevaar (Sander); J.N.M. IJzermans (Jan); M. Pescatori (Mario); A. Stubbs (Andrew); W.F.J. van IJcken (Wilfred); M.H. Dahlke (Marc); E. Eggenhofer (Elke); W. Weimar (Willem); M.J. Hoogduijn (Martin)

    2010-01-01

    textabstractThere is emerging interest in the application of mesenchymal stem cells (MSC) for the prevention and treatment of autoimmune diseases, graft-versus-host disease and allograft rejection. It is, however, unknown how inflammatory conditions affect phenotype and function of MSC. Adipose tiss

  9. 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

    Aim: This study investigated the effect of repeated infusions of recombinant human erythropoietin (EPO) on markers of inflammation in patients with affective disorders and whether any changes in inflammatory markers were associated with improvements on verbal memory. Methods: In total, 83 patients...... 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...... and change 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...

  10. Pioglitazone does not affect vascular or inflammatory responses after endotoxemia in humans.

    Science.gov (United States)

    Schaller, G; Kolodjaschna, J; Pleiner, J; Mittermayer, F; Kapiotis, S; Schmetterer, L; Wolzt, M

    2008-08-01

    PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.

  11. 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

  12. Food Restriction Affects Inflammatory Response and Nutritional State in Tuco-tucos (Ctenomys talarum).

    Science.gov (United States)

    Merlo, Julieta Leticia; Cutrera, Ana Paula; Zenuto, Roxana Rita

    2016-12-01

    Insufficient or unbalanced food intake typically has a negative impact on immune responses. The understanding of this effect is, however, hampered by the effect that food has on general condition, which, in turn, affects immunity, and the interaction among general condition, immunocompetence, and concurrent infections. The goal of this study was to determine the effects of food restriction and methionine supplementation on immunity in tuco-tucos (Ctenomys talarum). Effects of diet manipulations on nutritional state, inflammatory response to phytohemagglutinin (PHA), and other immune parameters (bacterial killing capacity, natural antibodies, and leukocyte profile) were evaluated. Health and stress parameters and endoparasite loads were assessed to understand more deeply potential effects of treatments on immune status. Individuals under food restriction presented an altered nutritional state as well as increased stress levels (higher N: L ratios) compared with individuals fed ad libitum, and a marked reduction in the inflammatory response to PHA. Supplementation with methionine did not affect any of the parameters analyzed. Endoparasite loads were not affected by treatments. Our results support the idea that food insufficiency can modulate the individual's immune responsiveness through the lack of adequate essential nutrients, metabolic fuel and energetic reserves, or by a detrimental effect of the stress caused by nutrient limitation. We show that the response to PHA previously reported as nonenergetically costly for C. talarum, implies a nutritional cost; an opposite pattern to that previously found for the adaptive antibody response to sheep red blood cells in the same species.

  13. 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.

  14. Diagnosis and management of atherosclerotic cardiovascular disease in chronic kidney disease: a review.

    Science.gov (United States)

    Mathew, Roy O; Bangalore, Sripal; Lavelle, Michael P; Pellikka, Patricia A; Sidhu, Mandeep S; Boden, William E; Asif, Arif

    2016-12-28

    Patients with chronic kidney disease (CKD) have a high prevalence of atherosclerotic cardiovascular disease, likely reflecting the presence of traditional risk factors. A greater distinguishing feature of atherosclerotic cardiovascular disease in CKD is the severity of the disease, which is reflective of an increase in inflammatory mediators and vascular calcification secondary to hyperparathyroidism of renal origin that are unique to patients with CKD. Additional components of atherosclerotic cardiovascular disease that are prominent in patients with CKD include microvascular disease and myocardial fibrosis. Therapeutic interventions that minimize cardiovascular events related to atherosclerotic cardiovascular disease in patients with CKD, as determined by well-designed clinical trials, are limited to statins. Data are lacking regarding other available therapeutic measures primarily due to exclusion of patients with CKD from major trials studying cardiovascular disease. Data from well-designed randomized controlled trials are needed to guide clinicians who care for this high-risk population in the management of atherosclerotic cardiovascular disease to improve clinical outcomes.

  15. 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.

  16. 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

    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...

  17. Atherosclerotic Human Aorta

    Directory of Open Access Journals (Sweden)

    Igor A. Sobenin

    2011-01-01

    Full Text Available We have evaluated the binding of sialylated and desialylated lipoproteins to collagen isolated from the proteoglycan and musculoelastic layers of intima and media of uninvolved human aorta and atherosclerotic lesions. Comparing various collagen preparations from the uninvolved intima-media, the binding of sialylated apoB-containing lipoproteins was best to collagen from the intimal PG-rich layer. Binding of sialylated apoB-containing lipoproteins to collagen from this layer of fatty streak and fibroatheroma was 1.4- and 3.1-fold lower, respectively, in comparison with normal intima. Desialylated VLDL versus sialylated one exhibited a greater binding (1.4- to 3.0-fold to all the collagen preparations examined. Desialylated IDL and LDL showed a higher binding than sialylated ones when collagen from the intimal layers of fibroatheroma was used. Binding of desialylated HDL to collagen from the intimal PG-rich layer of normal tissue, initial lesion, and fatty streak was 1.2- to 2.0-fold higher compared with sialylated HDL.

  18. 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.

  19. 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...

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Plasma inflammatory and vascular homeostasis biomarkers increase during human pregnancy but are not affected by oily fish intake.

    Science.gov (United States)

    García-Rodríguez, Cruz E; Olza, Josune; Aguilera, Concepción M; Mesa, María D; Miles, Elizabeth A; Noakes, Paul S; Vlachava, Maria; Kremmyda, Lefkothea-Stella; Diaper, Norma D; Godfrey, Keith M; Calder, Philip C; Gil, Angel

    2012-07-01

    The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P pregnancy progressed (P pregnancy, they are not affected by the increased intake of farmed salmon.

  5. 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.

  6. 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.

  7. 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...

  8. Adventitial inflammation and its interaction with intimal atherosclerotic lesions

    Directory of Open Access Journals (Sweden)

    Mohammadreza eAkhavanpoor

    2014-08-01

    Full Text Available The presence of adventitial inflammation in correlation with atherosclerotic lesions has been recognized for decades. In the last years, several studies have investigated the relevance and impact of adventitial inflammation on atherogenesis. In the abdominal aorta of elderly Apoe-/- mice, adventitial inflammatory structures were characterized as organized ectopic lymphoid tissue, and therefore termed adventitial tertiary lymphoid organs (ATLOs. These ATLOs possess similarities in development, structure and function to secondary lymphoid organs. A crosstalk between intimal atherosclerotic lesions and ATLOs has been suggested, and several studies could demonstrate a potential role for medial vascular smooth muscle cells in this process. We here review the development, phenotypic characteristics, and function of ATLOs in atherosclerosis. Furthermore, we discuss the possible role of medial vascular smooth muscle cells and their interaction between plaque and ATLOs.

  9. 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.

  10. Non-steroidal anti-inflammatory drugs affect the methotrexate transport in IEC-6 cells.

    Science.gov (United States)

    Sosogi, Aiko; Gao, Feng; Tomimatsu, Takashi; Hirata, Koji; Horie, Toshiharu

    2003-06-13

    Methotrexate (MTX) is used not only for the cancer chemotherapy but also for the treatment of rheumatic disease, often together with non-steroidal anti-inflammatory drugs (NSAIDs). MTX is actively cotransported with H(+) in the small intestine, mediated by a reduced folate carrier (RFC). The coadministration of some NSAIDs with MTX to rats caused a decrease of MTX absorption through the small intestine. This may be due to the uncoupling effect of oxidative phosphorylation of the NSAIDs. The present study investigated whether flufenamic acid, diclofenac and indomethacin, NSAIDs, decreased ATP content of rat-derived intestinal epithelial cell line IEC-6 cells and affected the MTX transport in IEC-6 cells. The MTX uptake in IEC-6 cells was dependent on medium pH and maximum around pH 4.5-5.5. The MTX uptake was composed of a transport inhibited by 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS) and a non-saturable one. The DIDS-sensitive component in the MTX uptake showed a saturation kinetics (Michaelis-Menten constant (Km): 3.91 +/- 0.52 microM, Maximum velocity (Vmax): 94.66 +/- 6.56 pmol/mg protein/5 min). The cellular ATP content in IEC-6 cells decreased significantly at 30 min after the cells were started to incubate with the NSAIDs (250 microM flufenamic acid, 500 microM diclofenac and 500 microM indomethacin). The MTX uptake in IEC-6 cells in the presence of the NSAIDs decreased with the reduction of cellular ATP content and showed a good correlation with the ATP content (correlation coefficient: 0.982). Thus it seems likely that the ATP content in IEC-6 cells with the NSAIDs decreased due to the uncoupling effect of oxidative phosphorylation of the NSAIDs, resulting in the inhibition of the secondary active transport of MTX in IEC-6 cells. The present results also suggest that IEC-6 cells are useful to evaluate the drug interaction relating to this carrier system.

  11. Pro-inflammatory cytokines affect pancreatic carcinoma cell. Endothelial cell interactions

    NARCIS (Netherlands)

    M. ten Kate (Miranda); L.J. Hofland (Leo); P.M. van Koetsveld (Peter); J. Jeekel (Hans); C.H.J. van Eijck (Casper)

    2006-01-01

    textabstractOBJECTIVES: The potential role of surgery-induced pro-inflammatory cytokines on the development of tumor recurrence in pancreatic cancer was investigated. MAIN OUTCOME MEASURES: The adhesion of 3 human pancreatic carcinoma cell lines, PanC1, MiaPaCa and BxPC3 to monolay

  12. Numerical analysis of the cooling effect of blood over inflamed atherosclerotic plaque.

    Science.gov (United States)

    Kim, Taehong; Ley, Obdulia

    2008-06-01

    Atherosclerotic plaques with high likelihood of rupture often show local temperature increase with respect to the surrounding arterial wall temperature. In this work, atherosclerotic plaque temperature was numerically determined during the different levels of blood flow reduction produced by the introduction of catheters at the vessel lumen. The temperature was calculated by solving the energy equation and the Navier-Stokes equations in 2D idealized arterial models. Arterial wall temperature depends on three basic factors: metabolic activity of the inflammatory cells embedded in the plaque, heat convection due to luminal blood flow, and heat conduction through the arterial wall and plaque. The calculations performed serve to simulate transient blood flow reduction produced by the presence of thermography catheters used to measure arterial wall temperature. The calculations estimate the spatial and temporal alterations in the cooling effect of blood flow and plaque temperature during the measurement process. The mathematical model developed provides a tool for analyzing the contribution of factors known to affect heat transfer at the plaque surface. Blood flow reduction leads to a nonuniform temperature increase ranging from 0.1 to 0.25 degrees Celsius in the plaque/lumen interface of the arterial geometries considered in this study. The temperature variation as well as the Nusselt number calculated along the plaque surface strongly depended on the arterial geometry and distribution of inflammatory cells. The calculations indicate that the minimum required time to obtain a steady temperature profile after arterial occlusion is 6 s. It was seen that in arteries with geometries involving bends, the temperature profiles appear asymmetrical and lean toward the downstream edge of the plaque.

  13. 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....

  14. Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microRNA.

    Science.gov (United States)

    Kim, Seong-Min; Lim, So-Mang; Yoo, Jeong-Ah; Woo, Moon-Jea; Cho, Kyung-Hyun

    2015-11-01

    Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22 ± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.

  15. 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 ...

  16. 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

  17. Whole grains protect against atherosclerotic cardiovascular disease.

    Science.gov (United States)

    Anderson, James W

    2003-02-01

    Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in most Western countries. Nutrition factors contribute importantly to this high risk for ASCVD. Favourable alterations in diet can reduce six of the nine major risk factors for ASCVD, i.e. high serum LDL-cholesterol levels, high fasting serum triacylglycerol levels, low HDL-cholesterol levels, hypertension, diabetes and obesity. Wholegrain foods may be one the healthiest choices individuals can make to lower the risk for ASCVD. Epidemiological studies indicate that individuals with higher levels (in the highest quintile) of whole-grain intake have a 29 % lower risk for ASCVD than individuals with lower levels (lowest quintile) of whole-grain intake. It is of interest that neither the highest levels of cereal fibre nor the highest levels of refined cereals provide appreciable protection against ASCVD. Generous intake of whole grains also provides protection from development of diabetes and obesity. Diets rich in wholegrain foods tend to decrease serum LDL-cholesterol and triacylglycerol levels as well as blood pressure while increasing serum HDL-cholesterol levels. Whole-grain intake may also favourably alter antioxidant status, serum homocysteine levels, vascular reactivity and the inflammatory state. Whole-grain components that appear to make major contributions to these protective effects are: dietary fibre; vitamins; minerals; antioxidants; phytosterols; other phytochemicals. Three servings of whole grains daily are recommended to provide these health benefits.

  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...

  19. Forming a support group for people affected by inflammatory bowel disease

    Science.gov (United States)

    Swarup, Nidhi; Nayak, Saumya; Lee, Jessie; Pai Raikar, Srinivas; Hou, David; Sockalingam, Senthil; Lee, Ken J

    2017-01-01

    Inflammatory bowel disease (IBD) – primarily Crohn’s disease and ulcerative colitis – is a debilitating lifelong condition with significant health and economic costs. From diagnosis to management, IBD can cause huge psychosocial concerns to patients and their caregivers. This study reports an experience of a Crohn’s patient, leading to the formation of the first IBD patient support group in Singapore and how this group has evolved in the last 4 years in supporting other IBD patients. IBD patient advocacy and/or support groups facilitate open conversations on patients’ fears, concerns, preferences and needs, and may potentially improve disease knowledge and quality of life for individuals with the condition or their families. PMID:28255233

  20. Autonomic nervous system modulation affects the inflammatory immune response in mice with acute Chagas disease.

    Science.gov (United States)

    Machado, Marcus Paulo Ribeiro; Rocha, Aletheia Moraes; de Oliveira, Lucas Felipe; de Cuba, Marília Beatriz; de Oliveira Loss, Igor; Castellano, Lucio Roberto; Silva, Marcus Vinicius; Machado, Juliana Reis; Nascentes, Gabriel Antonio Nogueira; Paiva, Luciano Henrique; Savino, Wilson; Junior, Virmondes Rodrigues; Brum, Patricia Chakur; Prado, Vania Ferreira; Prado, Marco Antonio Maximo; Silva, Eliane Lages; Montano, Nicola; Ramirez, Luis Eduardo; Dias da Silva, Valdo Jose

    2012-11-01

    The aim of the present study was to evaluate the effects of changes to the autonomic nervous system in mice during the acute phase of Chagas disease, which is an infection caused by the parasite Trypanosoma cruzi. The following types of mice were inoculated with T. cruzi (CHG): wild-type (WT) and vesicular acetylcholine transporter knockdown (KDVAChT) C57BL/6j mice; wild-type non-treated (NT) FVB mice; FVB mice treated with pyridostigmine bromide (PYR) or salbutamol (SALB); and β(2)-adrenergic receptor knockout (KOβ2) FVB mice. During infection and at 18-21 days after infection (acute phase), the survival curves, parasitaemia, electrocardiograms, heart rate variability, autonomic tonus and histopathology of the animals were evaluated. Negative control groups were matched for age, genetic background and treatment. The KDVAChT-CHG mice exhibited a significant shift in the electrocardiographic, autonomic and histopathological profiles towards a greater inflammatory immune response that was associated with a reduction in blood and tissue parasitism. In contrast, the CHG-PYR mice manifested reduced myocardial inflammation and lower blood and tissue parasitism. Similar results were observed in CHG-SALB animals. Unexpectedly, the KOβ2-CHG mice exhibited less myocardial inflammation and higher blood and tissue parasitism, which were associated with reduced mortality. These findings could have been due to the increase in vagal tone observed in the KOβ2 mice, which rendered them more similar to the CHG-PYR animals. In conclusion, our results indicate a marked immunomodulatory role for the parasympathetic and sympathetic autonomic nervous systems, which inhibit both the inflammatory immune response and parasite clearance during the acute phase of experimental Chagas heart disease in mice.

  1. 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

  2. Forming a support group for people affected by inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Swarup N

    2017-02-01

    Full Text Available Nidhi Swarup,1 Saumya Nayak,2 Jessie Lee,2 Srinivas Pai Raikar,2 David Hou,2 Senthil Sockalingam,2 Ken J Lee2 1Crohn’s and Colitis Society of Singapore (CCSS, The Arcadia, 2QuintilesIMS, Science Park One, Singapore Abstract: Inflammatory bowel disease (IBD – primarily Crohn’s disease and ulcerative colitis – is a debilitating lifelong condition with significant health and economic costs. From diagnosis to management, IBD can cause huge psychosocial concerns to patients and their caregivers. This study reports an experience of a Crohn’s patient, leading to the formation of the first IBD patient support group in Singapore and how this group has evolved in the last 4 years in supporting other IBD patients. IBD patient advocacy and/or support groups facilitate open conversations on patients’ fears, concerns, preferences and needs, and may potentially improve disease knowledge and quality of life for individuals with the condition or their families. Keywords: patient advocacy groups, Crohn’s disease, ulcerative colitis, patients, caregivers

  3. Timing of adding blood to prime affects inflammatory response to neonatal cardiopulmonary bypass.

    Science.gov (United States)

    Schmidt, Benjamin S; Jordan, James E; Lane, Magan R; DiPasquale, Vanessa M; Graf, Lori P; Ootaki, Yoshio; Ungerleider, Ross M

    2016-07-08

    Complications from systemic inflammation are reported in neonates following exposure to cardiopulmonary bypass. Although the use of asanguinous primes can reduce these complications, in neonates, this can result in significant haemodilution, requiring addition of blood. This study investigates whether the addition of blood after institution of bypass alters the inflammatory response compared with a blood prime. Neonatal swine were randomised into four groups: blood prime, blood after bypass but before cooling, blood after cooling but before low flow, and blood after re-warming. All groups were placed on central bypass, cooled, underwent low flow, and then re-warmed for a total bypass time of 2 hours. Although haematocrit values between groups varied throughout bypass, all groups ended with a similar value. Although they spent time with a lower haematocrit, asanguinous prime groups did not have elevated lactate levels at the end of bypass compared with blood prime. Asanguinous primes released less tumour necrosis factor α than blood primes (p=0.023). Asanguinous primes with blood added on bypass produced less interleukin 10 and tumour necrosis factor α (p=0.006, 0.019). Animals receiving blood while cool also showed less interleukin 10 and tumour necrosis factor α production than those that received blood warm (p=0.026, 0.033). Asanguinous primes exhibited less oedema than blood primes, with the least body weight gain noted in the end cool group (p=0.011). This study suggests that using an asanguinous prime for neonates being cooled to deep hypothermia is practical, and the later addition of blood reduces inflammation.

  4. 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.

  5. 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.

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

    Science.gov (United States)

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

    2016-12-09

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

  7. 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.

  8. 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.

  9. Inflammatory neuropathies.

    Science.gov (United States)

    Whitesell, Jackie

    2010-09-01

    Inflammatory neuropathies are acquired disorders of peripheral nerves and occasionally of the central nervous system that can affect individuals at any age. The course can be monophasic, relapsing, or progressive. Inflammatory neuropathies are classified as acute or chronic. The acute form reaches a nadir by 4 weeks and the chronic form over 8 weeks or greater. The most common example of an acute inflammatory neuropathy is acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is part of the Guillain-Barré syndrome (GBS). The most common chronic inflammatory neuropathy is chronic inflammatory demyelinating polyradiculopathy (CIDP). Other chronic inflammatory neuropathies are multifocal motor neuropathy (MMN) and the Lewis-Sumner syndrome. The Fisher syndrome and Bickerstaff brainstem encephalitis occur acutely and have clinical overlap with AIDP.

  10. 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

  11. Polymorphism of the NFKB1 affects the serum inflammatory levels of IL-6 in Hashimoto thyroiditis in a Turkish population.

    Science.gov (United States)

    Koc, Arzuhan; Batar, Bahadir; Celik, Ozlem; Onaran, Ilhan; Tasan, Ertugrul; Sultuybek, Gonul Kanigur

    2014-07-01

    Hashimoto thyroiditis (HT) is a chronic inflammatory autoimmune disease of thyroid gland affected by interaction of multiple genes and various cytokines. Variants in the genes coding for the NFKB and IKB proteins can be potentially involved in the development of the inflammatory diseases. NFKB, a key transcription factor of the regulation of immune responses, is interesting candidate for association studies about autoimmune disorder. The aim of the present study was to investigate the relationship between NFKB1 and NFKBIA (NFKB1 inhibitor gene) polymorphisms, and the risk of HT in a Turkish Population in the context of IL-6 serum levels which may contribute to susceptibility to the disease. We analyzed the distribution of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms using PCR-RFLP method and IL-6 serum levels using ELISA method in 120 HT patients and 190 healthy controls in Turkish population. Although, there was no statistical significant difference in distribution of the genotypes and alleles of NFKB1-94ins/del ATTG or NFKBIA 3'UTR A→G polymorphisms in patients and control subjects as single, ins/ins/GG combined genotype had protective effect on the disease when compared to ins/ins/AG combined genotype as combined genotypes of both polymorphisms. In addition to this finding, IL-6 serum levels in HT patients with del/del genotype were significantly higher than in patients with del/ins genotype (p<0.001). According to the combined genotype analysis of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms, IL-6 levels were also higher in patients with del/del genotype when at least one G allele existing (p=0.007). Therefore, our findings suggest that the functional promoter NFKB1-94ins/del ATTG polymorphism was significantly associated with population HT disease through acting by directly modulating IL-6 serum levels.

  12. 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.

  13. 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.

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

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    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

  15. Functional Heterogeneity of Nadph Oxidases in Atherosclerotic and Aneurysmal Diseases

    Science.gov (United States)

    Kigawa, Yasuyoshi; Lei, Xiao-Feng; Kim-Kaneyama, Joo-ri; Miyazaki, Akira

    2017-01-01

    NADPH oxidases (NOX) are enzymes that catalyze the production of reactive oxygen species (ROS). Four species of NOX catalytic homologs (NOX1, NOX2, NOX4, and NOX5) are reportedly expressed in vascular tissues. The pro-atherogenic roles of NOX1, NOX2, and their organizer protein p47phox were manifested, and it was noted that the hydrogen peroxide-generating enzyme NOX4 possesses atheroprotective effects. Loss of NOX1 or p47phox appears to ameliorate murine aortic dissection and subsequent aneurysmal diseases; in contrast, the ablation of NOX2 exacerbates the aneurysmal diseases. It is possible that the loss of NOX2 activates inflammatory cascades in macrophages in the lesions. Roles of NOX5 in vascular functions are currently undetermined, owing to the absence of this enzyme in rodents and the limitation of the experimental procedure. Thus, it is possible that the NOX family of enzymes exhibits heterogeneity in the atherosclerotic diseases. In this aspect, subtype-selective NOX inhibitor may be promising when NOX systems serve as a molecular target for atherosclerotic and aneurysmal diseases. PMID:27476665

  16. Swimming exercise and diphenyl diselenide-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats.

    Science.gov (United States)

    Leite, Marlon R; Cechella, José L; Mantovani, Anderson C; Duarte, Marta M M F; Nogueira, Cristina W; Zeni, Gilson

    2015-01-01

    The increase in the inflammatory process is one of the main factors that contribute to aging. The aim of this study was to investigate the effects of a diphenyl diselenide (PhSe)2-supplemented diet (1p.p.m., 4weeks) and swimming exercise (3% of body weight, 20min per day, 4weeks) on the serum levels of cytokines in Wistar rats of different ages. The results demonstrated an increase in the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNFα and INFγ) and a decrease in the levels of IL-10, an anti-inflammatory cytokine, with age. In middle-age rats, the swimming exercise and (PhSe)2-supplemented diet decreased serum levels of pro-inflammatory cytokines and increased the levels of IL-10. By contrast, in old rats the swimming exercise protocol increased the serum levels of pro-inflammatory cytokines and decreased the levels IL-10. Diet supplemented with (PhSe)2 did not alter the serum levels of cytokines in old rats. Middle-age and old rats subjected to swimming exercise and supplemented with (PhSe)2 in the diet had a decrease in the serum levels of pro-inflammatory cytokines and an increase in the levels of IL-10. This study demonstrated that swimming exercise and (PhSe)2-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats. (PhSe)2 supplemented in the diet had an anti-inflammatory effect, similar to that of induced by swimming exercise, in middle-age rats and reversed the pro-inflammatory effects of swimming exercise in old rats.

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

    Science.gov (United States)

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

    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. PMID:25632316

  18. 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.

  19. 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

  20. Inflammatory Myopathies

    Science.gov (United States)

    ... of chronic, or persistent, inflammatory myopathy are polymyositis, dermatomyositis, and inclusion body myositis. What causes these disorders? ... disorders may affect both adults and children, although dermatomyositis is the most common chronic form in children. ...

  1. Nonsteroidal anti-inflammatory drugs modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways

    Science.gov (United States)

    Mozolewski, Paweł; Moskot, Marta; Jakóbkiewicz-Banecka, Joanna; Węgrzyn, Grzegorz; Bocheńska, Katarzyna; Banecki, Bogdan; Gabig-Cimińska, Magdalena

    2017-01-01

    In this report, selected non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin and nimesulide, and analgesics acetaminophen, alone, as well as in combination with isoflavone genistein as potential glycosaminoglycan (GAG) metabolism modulators were considered for the treatment of mucopolysaccharidoses (MPSs) with neurological symptoms due to the effective blood-brain barrier (BBB) penetration properties of these compounds. We found that indomethacin and nimesulide, but not acetaminophen, inhibited GAG synthesis in fibroblasts significantly, while the most pronounced impairment of glycosaminoglycan production was observed after exposure to the mixture of nimesulide and genistein. Phosphorylation of the EGF receptor (EGFR) was inhibited even more effective in the presence of indomethacin and nimesulide than in the presence of genistein. When examined the activity of phosphatidylinositol-3-kinase (PI3K) production, we observed its most significant decrease in the case of fibroblast exposition to nimesulide, and afterwards to indomethacin and genistein mix, rather than indomethacin used alone. Some effects on expression of individual GAG metabolism-related and lysosomal function genes, and significant activity modulation of a number of genes involved in intracellular signal transduction pathways and metabolism of DNA and proteins were detected. This study documents that NSAIDs, and their mixtures with genistein modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways. PMID:28240227

  2. 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.

  3. The action of Metaloproteinases in the Atherosclerotic Diseases

    Directory of Open Access Journals (Sweden)

    Álvaro Luís Müller da Fonseca

    2014-11-01

    Full Text Available Cardiovascular diseases represent the main cause of morbidity and mortality in the world and are epidemic events involving the atherosclerosis and coronary artery disease in particular. There are a wide variety of factors and markers associated with the development and aggravation of these diseases, including atherosclerosis. Subclinical Atherosclerosis can be determined by serum inflammatory markers present in the atherogenic process. Such markers can take a direct or indirect indicator role on atherosclerotic cardiovascular disease. The extracellular matrix metalloproteinases are biomarkers closely related into modifying and remodeling of vascular wall and other tissues and can represent predictive value patterns to support diagnosis. This review discusses the function and types of matrix metalloproteinases and its use as an indicator of support for the diagnosis of atherosclerosis.

  4. Exploration and application of nanomedicine in atherosclerotic disease

    NARCIS (Netherlands)

    Lobatto, M.E.

    2016-01-01

    In this thesis the potential of nanomedicine to treat atherosclerotic disease is examined. The research presented addresses the development and characterization of various nanodrugs, nanoparticle targeting concepts in atherosclerotic disease, as well as the use of noninvasive imaging to characterize

  5. 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.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

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    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.

  8. 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

  9. 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,

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

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    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.

  11. Vaporization of atherosclerotic plaques by spark erosion

    NARCIS (Netherlands)

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

    1985-01-01

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

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. Fluorescent activated cell sorting: an effective approach to study dendritic cell subsets in human atherosclerotic plaques.

    Science.gov (United States)

    Van Brussel, Ilse; Ammi, Rachid; Rombouts, Miche; Cools, Nathalie; Vercauteren, Sven R; De Roover, Dominique; Hendriks, Jeroen M H; Lauwers, Patrick; Van Schil, Paul E; Schrijvers, Dorien M

    2015-02-01

    Different immune cell types are present within atherosclerotic plaques. Dendritic cells (DC) are of special interest, since they are considered as the 'center of the immuniverse'. Identifying inflammatory DC subtypes within plaques is important for a better understanding of the lesion pathogenesis and pinpoints their contribution to the atherosclerotic process. We have developed a flow cytometry-based method to characterize and isolate different DC subsets (i.e. CD11b(+), Clec9A(+) and CD16(+) conventional (c)DC and CD123(+) plasmacytoid (p)DC) in human atherosclerotic plaques. We revealed a predominance of pro-inflammatory CD11b(+) DC in advanced human lesions, whereas atheroprotective Clec9A(+) DC were almost absent. CD123(+) pDC and CD16(+) DC were also detectable in plaques. Remarkably, plaques from distinct anatomical locations exhibited different cellular compositions: femoral plaques contained less CD11b(+) and Clec9A(+) DC than carotid plaques. Twice as many monocytes/macrophages were observed compared to DC. Moreover, relative amounts of T cells/B cells/NK cells were 6 times as high as DC numbers. For the first time, fluorescent activated cell sorting analysis of DC subsets in human plaques indicated a predominance of CD11b(+) cDC, in comparison with other DC subsets. Isolation of the different subsets will facilitate detailed functional analysis and may have significant implications for tailoring appropriate therapy.

  17. 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

  18. Bacterial Communities Associated with Atherosclerotic Plaques from Russian Individuals with Atherosclerosis.

    Science.gov (United States)

    Ziganshina, Elvira E; Sharifullina, Dilyara M; Lozhkin, Andrey P; Khayrullin, Rustem N; Ignatyev, Igor M; Ziganshin, Ayrat M

    2016-01-01

    Atherosclerosis is considered a chronic disease of the arterial wall and is the major cause of severe disease and death among individuals all over the world. Some recent studies have established the presence of bacteria in atherosclerotic plaque samples and suggested their possible contribution to the development of cardiovascular disease. The main objective of this preliminary pilot study was to better understand the bacterial diversity and abundance in human atherosclerotic plaques derived from common carotid arteries of individuals with atherosclerosis (Russian nationwide group) and contribute towards the further identification of a main group of atherosclerotic plaque bacteria by 454 pyrosequencing their 16S ribosomal RNA (16S rRNA) genes. The applied approach enabled the detection of bacterial DNA in all atherosclerotic plaques. We found that distinct members of the order Burkholderiales were present at high levels in all atherosclerotic plaques obtained from patients with atherosclerosis with the genus Curvibacter being predominant in all plaque samples. Moreover, unclassified Burkholderiales as well as members of the genera Propionibacterium and Ralstonia were typically the most significant taxa for all atherosclerotic plaques. Other genera such as Burkholderia, Corynebacterium and Sediminibacterium as well as unclassified Comamonadaceae, Oxalobacteraceae, Rhodospirillaceae, Bradyrhizobiaceae and Burkholderiaceae were always found but at low relative abundances of the total 16S rRNA gene population derived from all samples. Also, we found that some bacteria found in plaque samples correlated with some clinical parameters, including total cholesterol, alanine aminotransferase and fibrinogen levels. Finally, our study indicates that some bacterial agents at least partially may be involved in affecting the development of cardiovascular disease through different mechanisms.

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

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    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.

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

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    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.

  1. 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....... There was an increase in hs-TnT, but no significant difference between the melatonin-treated and placebo-treated groups. There were no significant differences in development of any of the circulating plasma markers between the two groups. Conclusion: Melatonin treatment did not result in reduction of inflammatory...

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

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    Rosa Sessa

    2013-07-01

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

  3. Local effects of atherosclerotic plaque on arterial distensibility.

    Science.gov (United States)

    Giannattasio, C; Failla, M; Emanuelli, G; Grappiolo, A; Boffi, L; Corsi, D; Mancia, G

    2001-11-01

    Hypertension, diabetes, and hypercholesterolemia are characterized by a reduction in arterial distensibility and by accelerated atherosclerosis. Whether arterial stiffening is an inherent feature of these conditions or just the consequence of the atherosclerotic clinical or subclinical lesions is not known, however. Our aim was to obtain information on this issue by directly measuring, in humans, arterial distensibility both at the site of an atherosclerotic lesion and at the proximal normal site. In 10 patients (8 men; mean+/-SEM age, 65.2+/-3.4 years) affected by monolateral hemodynamic significant internal carotid artery stenosis, we measured arterial distensibility (Wall Track System; PIE Medical) bilaterally, both at the internal carotid artery and at the common carotid artery level. In the common carotid artery, measurements were made 3 cm below the bifurcation. In the affected internal carotid artery, measurements were made at the plaque shoulder (wall thickness of 2 mm). Measurements were made in the contralateral internal carotid artery at a symmetrical level. Arterial wall thickness was measured in the same site of arterial distensibility. Arterial distensibility was less in the internal than in the common carotid artery, with a marked reduction at the plaque internal carotid artery level compared with the corresponding contralateral site (-45%, P<0.01). It was also less, however, in the common carotid artery branching into the atherosclerotic internal carotid artery than in the contralateral common carotid artery (-25%, P<0.05). Wall thickness was similar in the 2 common carotid arteries and obviously greater in the affected internal carotid artery than in the contralateral artery. Arterial distensibility was markedly less in the internal carotid artery where there was a plaque compared with the intact contralateral internal carotid artery; it was also less, however, in the common carotid artery of the affected side in comparison with the contralateral

  4. 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

  5. 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.

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

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    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

  7. Endoglin haplo-insufficiency modifies the inflammatory response in irradiated mouse hearts without affecting structural and mircovascular changes.

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    Ingar Seemann

    Full Text Available BACKGROUND: It is now widely recognized that radiotherapy of thoracic and chest wall tumors increases the long-term risk of cardiovascular damage although the underlying mechanisms are not fully elucidated. There is increasing evidence that microvascular damage is involved. Endoglin, an accessory receptor for TGF-β1, is highly expressed in damaged endothelial cells and may play a crucial role in cell proliferation and revascularization of damaged heart tissue. We have therefore specifically examined the role of endoglin in microvascular damage and repair in the irradiated heart. MATERIALS & METHODS: A single dose of 16 Gy was delivered to the heart of adult Eng(+/+ or Eng(+/- mice and damage was evaluated at 4, 20 and 40 weeks, relative to age-matched controls. Gated single photon emission computed tomography (gSPECT was used to measure cardiac geometry and function, and related to histo-morphology, microvascular damage (detected using immuno- and enzyme-histochemistry and gene expression (detected by microarray and real time PCR. RESULTS: Genes categorized according to known inflammatory and immunological related disease were less prominently regulated in irradiated Eng(+/- mice compared to Eng(+/+ littermates. Fibrosis related genes, TGF-β1, ALK 5 and PDGF, were only upregulated in Eng(+/+ mice during the early phase of radiation-induced cardiac damage (4 weeks. In addition, only the Eng(+/+ mice showed significant upregulation of collagen deposition in the early fibrotic phase (20 weeks after irradiation. Despite these differences in gene expression, there was no reduction in inflammatory invasion (CD45+cells of irradiated Eng(+/- hearts. Microvascular damage (microvascular density, alkaline phosphatase and von-Willebrand-Factor expression was also similar in both strains. CONCLUSION: Eng(+/- mice displayed impaired early inflammatory and fibrotic responses to high dose irradiation compared to Eng(+/+ littermates. This did not result in

  8. Divergent JAM-C Expression Accelerates Monocyte-Derived Cell Exit from Atherosclerotic Plaques.

    Science.gov (United States)

    Bradfield, Paul F; Menon, Arjun; Miljkovic-Licina, Marijana; Lee, Boris P; Fischer, Nicolas; Fish, Richard J; Kwak, Brenda; Fisher, Edward A; Imhof, Beat A

    2016-01-01

    Atherosclerosis, caused in part by monocytes in plaques, continues to be a disease that afflicts the modern world. Whilst significant steps have been made in treating this chronic inflammatory disease, questions remain on how to prevent monocyte and macrophage accumulation in atherosclerotic plaques. Junctional Adhesion Molecule C (JAM-C) expressed by vascular endothelium directs monocyte transendothelial migration in a unidirectional manner leading to increased inflammation. Here we show that interfering with JAM-C allows reverse-transendothelial migration of monocyte-derived cells, opening the way back out of the inflamed environment. To study the role of JAM-C in plaque regression we used a mouse model of atherosclerosis, and tested the impact of vascular JAM-C expression levels on monocyte reverse transendothelial migration using human cells. Studies in-vitro under inflammatory conditions revealed that overexpression or gene silencing of JAM-C in human endothelium exposed to flow resulted in higher rates of monocyte reverse-transendothelial migration, similar to antibody blockade. We then transplanted atherosclerotic, plaque-containing aortic arches from hyperlipidemic ApoE-/- mice into wild-type normolipidemic recipient mice. JAM-C blockade in the recipients induced greater emigration of monocyte-derived cells and further diminished the size of atherosclerotic plaques. Our findings have shown that JAM-C forms a one-way vascular barrier for leukocyte transendothelial migration only when present at homeostatic copy numbers. We have also shown that blocking JAM-C can reduce the number of atherogenic monocytes/macrophages in plaques by emigration, providing a novel therapeutic strategy for chronic inflammatory pathologies.

  9. Divergent JAM-C Expression Accelerates Monocyte-Derived Cell Exit from Atherosclerotic Plaques.

    Directory of Open Access Journals (Sweden)

    Paul F Bradfield

    Full Text Available Atherosclerosis, caused in part by monocytes in plaques, continues to be a disease that afflicts the modern world. Whilst significant steps have been made in treating this chronic inflammatory disease, questions remain on how to prevent monocyte and macrophage accumulation in atherosclerotic plaques. Junctional Adhesion Molecule C (JAM-C expressed by vascular endothelium directs monocyte transendothelial migration in a unidirectional manner leading to increased inflammation. Here we show that interfering with JAM-C allows reverse-transendothelial migration of monocyte-derived cells, opening the way back out of the inflamed environment. To study the role of JAM-C in plaque regression we used a mouse model of atherosclerosis, and tested the impact of vascular JAM-C expression levels on monocyte reverse transendothelial migration using human cells. Studies in-vitro under inflammatory conditions revealed that overexpression or gene silencing of JAM-C in human endothelium exposed to flow resulted in higher rates of monocyte reverse-transendothelial migration, similar to antibody blockade. We then transplanted atherosclerotic, plaque-containing aortic arches from hyperlipidemic ApoE-/- mice into wild-type normolipidemic recipient mice. JAM-C blockade in the recipients induced greater emigration of monocyte-derived cells and further diminished the size of atherosclerotic plaques. Our findings have shown that JAM-C forms a one-way vascular barrier for leukocyte transendothelial migration only when present at homeostatic copy numbers. We have also shown that blocking JAM-C can reduce the number of atherogenic monocytes/macrophages in plaques by emigration, providing a novel therapeutic strategy for chronic inflammatory pathologies.

  10. Metalloproteinases and advanced glycation end products: coupled navigation in atherosclerotic plaque pathophysiology?

    Science.gov (United States)

    Furfaro, A L; Sanguineti, R; Storace, D; Monacelli, F; Puzzo, A; Pronzato, M A; Odetti, P; Traverso, N

    2012-11-01

    Matrix metalloproteinases (MMPs), their inhibitors (TIMPs) and inflammatory cytokines, such as interleukin-1 (IL-1), are considered markers of evolution and/or instability of atherosclerotic plaques. Accumulation of Advanced Glycation Endproducts (AGE) is a well known phenomenon in diabetes and has also been considered in the pathogenesis of atherosclerosis. Aim of the present study was to analyse the levels of pentosidine, a fluorescent AGE, and to evaluate the expression of MMP-2, TIMP-3, and IL-1 in an ex vivo model of human advanced atherosclerotic plaques. We intended to test the possible correlation between pentosidine and markers of ECM remodelling and inflammation in the atherosclerotic process, and to investigate if classic risk factors, such as diabetes and hypertension, influenced these biochemical parameters. We found that diabetic plaques showed higher level of pentosidine, as expected, but much lower, or even undetectable, expression levels of MMP-2 and TIMP-3; IL-1 expression was not different between diabetic and non diabetic plaques. Hypertension did not influence any of these parameters. Although the statistical correlations between the expression of the considered genes and pentosidine did not reach significance, slight negative trends were noted between TIMP-3 and IL-1 expression vs. pentosidine content. We suggest that in mature diabetic plaques AGE accumulation can exert stabilizing effects on matrix proteins, while scanty cell presence leads to poor capacity of reactive responses, such as remodelling and inflammation.

  11. mRNA expression of genes involved in lipid efflux and matrix degradation in occlusive and ectatic atherosclerotic disease

    OpenAIRE

    Soumian, S; Gibbs, R.; Davies, A.; Albrecht, C.

    2005-01-01

    Background: Atherosclerotic plaque behaviour is influenced by intraplaque inflammation, matrix turnover, and the lipid core volume. Peroxisome proliferator activated receptor γ (PPARγ) modulates atherosclerosis by its anti-inflammatory and anti-protease activity. PPARγ promotes lipid efflux through the liver X receptor α (LXRα) and the ATP binding cassette transporter A1 (ABCA1). Matrix metalloproteinase 9 (MMP-9) and cyclooxygenase 2 (COX-2) are implicated in plaque instability.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Adrienne Müller

    2014-03-01

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

  14. 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.

  15. 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....

  16. Aorto-esophageal fistula secondary to penetrating atherosclerotic ulcer

    Directory of Open Access Journals (Sweden)

    Ranjana Gupta

    2012-01-01

    Full Text Available Aorto-esophageal fistula (AEF is a rare and life threatening condition, which can be rapidly fatal. More than half of such cases are secondary to aortic aneurysm rupture. There are only two previous reports describing AEF caused by penetrating atherosclerotic ulcer. We present multidetector computed tomography findings in a case of AEF secondary to penetrating atherosclerotic ulcer.

  17. The Impact of Intermittent and Repetitive Cold Stress Exposure on Endoplasmic Reticulum Stress and Instability of Atherosclerotic Plaques

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    Ming-Xiang Dai

    2014-07-01

    Full Text Available Background: The incidence of acute coronary syndrome caused by the rupture of atherosclerotic plaque and subsequent arterial thrombosis increases as the weather gets colder. However, the association between cold stress and atherosclerotic plaque rupture is currently unknown. Methods: An atherosclerotic plaque model was established in rabbits by balloon injury and a high-fat diet with or without cold stress (4°C, 1 hour per day, 20 weeks at the onset of modeling. Additionally, oxidized low-density lipoprotein (ox-LDL was applied to induce the formation of macrophage foam cells in vitro. Results: Serum lipid profiles and inflammatory cytokines (ox-LDL, high-sensitivity C-reactive protein, and interleukin-8 were significantly higher in cold stress-exposed rabbits than in controls (PConclusions: Cold stress may enhance the instability of atherosclerotic plaques through activating ERS and enhancing cell apoptosis. Up-regulated CHOP levels mediated by PERK and ATF6 and the activated IRE1-XBP1-JNK pathway contributed to the apoptosis of foam cells.

  18. Endovascular treatment of symptomatic intracranial atherosclerotic disease

    Directory of Open Access Journals (Sweden)

    Syed I Hussain

    2011-02-01

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

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

    Science.gov (United States)

    Orlando, Antonina; Colombo, Miriam; Prosperi, Davide; Gregori, Maria; Panariti, Alice; Rivolta, Ilaria; Masserini, Massimo; Cazzaniga, Emanuela

    2015-09-01

    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-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.

  20. 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.

  1. 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.

  2. 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.

  3. Modelling Affective Pain in Mice: Effects of Inflammatory Hypersensitivity on Place Escape/Avoidance Behaviour, Anxiety and Hedonic State

    DEFF Research Database (Denmark)

    Refsgaard, Louise Konradsen; Hoffmann-Petersen, Julie; Sahlholt, Maj;

    2016-01-01

    PEAP and other behavioural responses, namely anxiety-like behaviour, locomotor activity, and hedonic state. New Method A novel paradigm assessing the affective component of pain in mice was developed by modifying the setup known from rat studies: Animals were forced to stay 2x5 min in the light......, whereas locomotor activity was unaffected. A significant, albeit modest, reduction in saccharin preference was observed. PEAP responses showed no significant correlations with any other behavioural measure. Comparison with Existing Method and Conclusions The PEAP results suggest that this paradigm might...

  4. {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)

  5. Atherosclerotic plaque regression: fact or fiction?

    Science.gov (United States)

    Shanmugam, Nesan; Román-Rego, Ana; Ong, Peter; Kaski, Juan Carlos

    2010-08-01

    Coronary artery disease is the major cause of death in the western world. The formation and rapid progression of atheromatous plaques can lead to serious cardiovascular events in patients with atherosclerosis. The better understanding, in recent years, of the mechanisms leading to atheromatous plaque growth and disruption and the availability of powerful HMG CoA-reductase inhibitors (statins) has permitted the consideration of plaque regression as a realistic therapeutic goal. This article reviews the existing evidence underpinning current therapeutic strategies aimed at achieving atherosclerotic plaque regression. In this review we also discuss imaging modalities for the assessment of plaque regression, predictors of regression and whether plaque regression is associated with a survival benefit.

  6. 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.

  7. Potential Anti-Atherosclerotic Properties of Astaxanthin.

    Science.gov (United States)

    Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

    2016-02-05

    Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Dynamic modulation of inflammatory pain-related affective and sensory symptoms by optical control of amygdala metabotropic glutamate receptor 4.

    Science.gov (United States)

    Zussy, C; Gómez-Santacana, X; Rovira, X; De Bundel, D; Ferrazzo, S; Bosch, D; Asede, D; Malhaire, F; Acher, F; Giraldo, J; Valjent, E; Ehrlich, I; Ferraguti, F; Pin, J-P; Llebaria, A; Goudet, C

    2016-12-20

    Contrary to acute pain, chronic pain does not serve as a warning signal and must be considered as a disease per se. This pathology presents a sensory and psychological dimension at the origin of affective and cognitive disorders. Being largely refractory to current pharmacotherapies, identification of endogenous systems involved in persistent and chronic pain is crucial. The amygdala is a key brain region linking pain sensation with negative emotions. Here, we show that activation of a specific intrinsic neuromodulatory system within the amygdala associated with type 4 metabotropic glutamate receptors (mGlu4) abolishes sensory and affective symptoms of persistent pain such as hypersensitivity to pain, anxiety- and depression-related behaviors, and fear extinction impairment. Interestingly, neuroanatomical and synaptic analysis of the amygdala circuitry suggests that the effects of mGlu4 activation occur outside the central nucleus via modulation of multisensory thalamic inputs to lateral amygdala principal neurons and dorso-medial intercalated cells. Furthermore, we developed optogluram, a small diffusible photoswitchable positive allosteric modulator of mGlu4. This ligand allows the control of endogenous mGlu4 activity with light. Using this photopharmacological approach, we rapidly and reversibly inhibited behavioral symptoms associated with persistent pain through optical control of optogluram in the amygdala of freely behaving animals. Altogether, our data identify amygdala mGlu4 signaling as a mechanism that bypasses central sensitization processes to dynamically modulate persistent pain symptoms. Our findings help to define novel and more precise therapeutic interventions for chronic pain, and exemplify the potential of optopharmacology to study the dynamic activity of endogenous neuromodulatory mechanisms in vivo.Molecular Psychiatry advance online publication, 20 December 2016; doi:10.1038/mp.2016.223.

  13. 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

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

    Science.gov (United States)

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

    2017-04-01

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

  15. 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

  16. Primary Prevention of Atherosclerotic Cardiovascular Disease in Women.

    Science.gov (United States)

    McKibben, Rebeccah A; Al Rifai, Mahmoud; Mathews, Lena M; Michos, Erin D

    2016-01-01

    Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality among women. Despite improvements in cardiovascular disease prevention efforts, there remain gaps in cardiovascular disease awareness among women, as well as age and racial disparities in ASCVD outcomes for women. Disparity also exists in the impact the traditional risk factors confer on ASCVD risk between women and men, with smoking and diabetes both resulting in stronger relative risks in women compared to men. Additionally there are risk factors that are unique to women (such as pregnancy-related factors) or that disproportionally affect women (such as auto-immune disease) where preventive efforts should be targeted. Risk assessment and management must also be sex-specific to effectively reduce cardiovascular disease and improve outcomes among women. Evidence supports the use of statin therapy for primary prevention in women at higher ASCVD risk. However, some pause should be given to prescribing aspirin therapy in women without known ASCVD, with most evidence supporting the use of aspirin for women≥65 years not at increased risk for bleeding. This review article will summarize (1) traditional and non-traditional assessments of ASCVD risk and (2) lifestyle and pharmacologic therapies for the primary prevention of ASCVD in women.

  17. 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.

  18. Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Qin J

    2014-12-01

    Full Text Available Jinbao Qin,1,* Chen Peng,2,* Binghui Zhao,2,* Kaichuang Ye,1 Fukang Yuan,1 Zhiyou Peng,1 Xinrui Yang,1 Lijia Huang,1 Mier Jiang,1 Qinghua Zhao,3 Guangyu Tang,2 Xinwu Lu1,4 1Department of Vascular Surgery, Shanghai Ninth People’s Hospital Affiliated to Shanghai JiaoTong University, School of Medicine; 2Department of Radiology, Shanghai Tenth People’s Hospital Affiliated to Tongji University, School of Medicine; 3Department of Orthopaedics, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University; 4Vascular Center of Shanghai JiaoTong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS. Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs with polyethylene glycol (PEG and fluorescein isothiocyanate (FI coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 µM and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases. Keywords: atherosclerosis, CT, in vivo

  19. Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques

    Science.gov (United States)

    Fumagalli, Stefano; Perego, Carlo; Zangari, Rosalia; De Blasio, Daiana; Oggioni, Marco; De Nigris, Francesca; Snider, Francesco; Garred, Peter; Ferrante, Angela M. R.; De Simoni, Maria-Grazia

    2017-01-01

    Inflammatory mechanisms may be involved in atherosclerotic plaque rupture. By using a novel histology-based method to quantify plaque instability here, we assess whether lectin pathway (LP) of complement activation, a major inflammation arm, could represent an index of plaque instability. Plaques from 42 consecutive patients undergoing carotid endarterectomy were stained with hematoxylin-eosin and the lipid core, cholesterol clefts, hemorrhagic content, thickness of tunica media, and intima, including or not infiltration of cellular debris and cholesterol, were determined. The presence of ficolin-1, -2, and -3 and mannose-binding lectin (MBL), LP initiators, was assessed in the plaques by immunofluorescence and in plasma by ELISA. LP activation was assessed in plasma by functional in vitro assays. Patients presenting low stenosis (≤75%) had higher hemorrhagic content than those with high stenosis (>75%), indicating increased erosion. Increased hemorrhagic content and tunica media thickness, as well as decreased lipid core and infiltrated content were associated with vulnerable plaques and therefore used to establish a plaque vulnerability score that allowed to classify patients according to plaque vulnerability. Ficolins and MBL were found both in plaques’ necrotic core and tunica media. Patients with vulnerable plaques showed decreased plasma levels and intraplaque deposition of ficolin-2. Symptomatic patients experiencing a transient ischemic attack had lower plasma levels of ficolin-1. We show that the LP initiators are present within the plaques and their circulating levels change in atherosclerotic patients. In particular, we show that decreased ficolin-2 levels are associated with rupture-prone vulnerable plaques, indicating its potential use as marker for cardiovascular risk assessment in atherosclerotic patients. PMID:28360913

  20. MicroRNA-containing microvesicles regulating inflammation in association with atherosclerotic disease.

    Science.gov (United States)

    Hulsmans, Maarten; Holvoet, Paul

    2013-10-01

    In addition to intracellular organelles, eukaryotic cells contain extracellular organelles which are released, or shed, into the microenvironment. In practice, most human studies have examined mixed populations containing both exosomes and shedding microvesicles (also called ectosomes or microparticles); only a few studies have rigorously distinguished between the two. Accordingly, in this review, exosomes and shedding microvesicles are collectively called microvesicles. The first aim of this review was to discuss the role of microvesicles in cell-to-cell communication in general and in specific interactions between cells in chronic inflammation associated with atherosclerotic disease. Hereby, we focused on cell-specific microvesicles derived from platelets, endothelial cells and monocyte and monocyte-derived cells. The latter were also found to be associated with inflammation in obesity and type 2 diabetes prior to atherosclerotic disease, and cancer. Our second aim was to discuss specific changes in microvesicle content in relation with inflammation associated with metabolic and atherosclerotic disease, and cancer. Because many studies supported the putative diagnostic value of microRNAs, we emphasized therein changes in microRNA content rather than protein or lipid content. The most interesting microRNAs in inflammatory microvesicles in association with metabolic and cardiovascular diseases were found to be the let-7 family, miR-17/92 family, miR-21, miR-29, miR-126, miR-133, miR-146, and miR-155. These data warrant further investigation of the potential of microvesicles as putative biomarkers and as novel carriers for the cell-specific transfer of microRNAs and other therapeutic agents.

  1. 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.

  2. Prenatal stress enhances severity of atherosclerosis in the adult apolipoprotein E-deficient mouse offspring via inflammatory pathways.

    Science.gov (United States)

    Ho, H; Lhotak, S; Solano, M E; Karimi, K; Pincus, M K; Austin, R C; Arck, P

    2013-02-01

    Atherosclerosis is the underlying cause of cardiovascular disease and stroke. Endothelial cell dysfunctions are early events in atherosclerosis, resulting in the recruitment of circulating monocytes. The immune system can elicit an inflammatory response toward the atherosclerotic lesion, thereby accelerating lesion growth. Risk factors for atherosclerosis include hypertension, smoking, stress perception or low birth weight. As prenatal stress challenge decreases the birth weight and affects the offspring's postnatal immune response, we aimed to investigate whether prenatal stress contributes to the development of atherosclerosis in mice. Syngenic pregnant apolipoprotein E-deficient (apoE-/-) dams were exposed to sound stress on gestation days 12.5 and 14.5. The presence and size of atherosclerotic plaques in the offspring at the age of 15 weeks was evaluated by histomorphology, accompanied by flow cytometric analysis of the frequency and phenotype of monocytes/macrophages and regulatory T (Treg) cells in the blood. Further, cytokine secretion of peripheral blood lymphocytes was analyzed. In response to prenatal stress challenge, an increased frequency of large atherosclerotic plaques was detectable in apoE-/- offspring, which was particularly profound in females. Prenatal stress also resulted in alterations of the offspring's immune response, such as a decreased frequency of Treg cells in blood, alterations of macrophage populations in blood and an increased secretion of inflammatory cytokines. We provide novel evidence that prenatally stressed adult offspring show an increased severity of atherosclerosis. As Treg cells are key players in dampening inflammation, the observed increase in atherosclerosis may be due to the lack of Treg cell frequency. Future interdisciplinary research is urgently required to understand the developmental origin of prenatal stress-induced atherosclerosis. The availability of our model may facilitate and foster such research endeavors.

  3. 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.

  4. Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy.

    Directory of Open Access Journals (Sweden)

    Abigail S Haka

    Full Text Available The progressive accumulation of monocyte-derived cells in the atherosclerotic plaque is a hallmark of atherosclerosis. However, it is now appreciated that monocytes represent a heterogeneous circulating population of cells that differ in functionality. New approaches are needed to investigate the role of monocyte subpopulations in atherosclerosis since a detailed understanding of their differential mobilization, recruitment, survival and emigration during atherogenesis is of particular importance for development of successful therapeutic strategies. We present a novel methodology for the in vivo examination of monocyte subpopulations in mouse models of atherosclerosis. This approach combines cellular labeling by fluorescent beads with multiphoton microscopy to visualize and monitor monocyte subpopulations in living animals. First, we show that multiphoton microscopy is an accurate and timesaving technique to analyze monocyte subpopulation trafficking and localization in plaques in excised tissues. Next, we demonstrate that multiphoton microscopy can be used to monitor monocyte subpopulation trafficking in atherosclerotic plaques in living animals. This novel methodology should have broad applications and facilitate new insights into the pathogenesis of atherosclerosis and other inflammatory diseases.

  5. Peroxisome proliferator-activated receptor {alpha} agonism prevents renal damage and the oxidative stress and inflammatory processes affecting the brains of stroke-prone rats.

    Science.gov (United States)

    Gelosa, Paolo; Banfi, Cristina; Gianella, Anita; Brioschi, Maura; Pignieri, Alice; Nobili, Elena; Castiglioni, Laura; Cimino, Mauro; Tremoli, Elena; Sironi, Luigi

    2010-11-01

    A growing body of evidence suggests that chronic kidney disease is a significant risk for cardiovascular events and stroke regardless of traditional risk factors. The aim of this study was to examine the effects of peroxisome proliferator-activated receptor (PPAR) agonists on the tissue damage affecting salt-loaded spontaneously hypertensive stroke-prone rats ( SHRSPs), an animal model that develops a complex pathology characterized by systemic inflammation, hypertension, and proteinuria and leads to end-organ injury (initially renal and subsequently cerebral). Compared with the PPARγ agonist rosiglitazone, the PPARα ligands fenofibrate and clofibrate significantly increased survival (p damage, and glomerular sclerosis, reduced the number of ED-1-positive cells and collagen accumulation, and decreased the renal expression of interleukin-1β, transforming growth factor β, and monocyte chemoattractant protein 1. It also prevented the plasma and urine accumulation of acute-phase and oxidized proteins, suggesting that the protection induced by PPARα agonists was at least partially caused by their anti-inflammatory and antioxidative properties. The results of this study demonstrate that PPAR agonism has beneficial effects on spontaneous brain and renal damage in SHRSPs by inhibiting systemic inflammation and oxidative stress, and they support carrying out future studies aimed at evaluating the effect of PPARα agonists on proteinuria and clinical outcomes in hypertensive patients with renal disease at increased risk of stroke.

  6. Dyslipidemia rather than Type 2 Diabetes Mellitus or Chronic Periodontitis Affects the Systemic Expression of Pro- and Anti-Inflammatory Genes

    Science.gov (United States)

    Corbi, Sâmia Cruz Tfaile; Bastos, Alliny De Souza; Dos Santos, Raquel Alves; Orrico, Silvana Regina Perez

    2017-01-01

    A high percentage of type 2 diabetes mellitus (T2D) patients are also affected by dyslipidemia and chronic periodontitis (CP), but no studies have determined the gene expression in patients that are simultaneously affected by all three diseases. We investigated the systemic expression of immune-related genes in T2D, dyslipidemia, and CP patients. One hundred and fifty patients were separated into five groups containing 30 individuals each: (G1) poorly controlled T2D with dyslipidemia and CP; (G2) well-controlled T2D with dyslipidemia and CP; (G3) normoglycemic individuals with dyslipidemia and CP; (G4) healthy individuals with CP; (G5) systemic and periodontally healthy individuals. Blood analyses of lipid and glycemic profiles were carried out. The expression of genes, including IL10, JAK1, STAT3, SOCS3, IP10, ICAM1, IFNA, IFNG, STAT1, and IRF1, was investigated by RT-qPCR. Patients with dyslipidemia demonstrated statistically higher expression of the IL10 and IFNA genes, while IFNG, IP10, IRF1, JAK1, and STAT3 were lower in comparison with nondyslipidemic patients. Anti-inflammatory genes, such as IL10, positively correlated with parameters of glucose, lipid, and periodontal profiles, while proinflammatory genes, such as IFNG, were negatively correlated with these parameters. We conclude that dyslipidemia appears to be the primary disease that is associated with gene expression of immune-related genes, while parameters of T2D and CP were correlated with the expression of these important immune genes. PMID:28316372

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

    Directory of Open Access Journals (Sweden)

    Filippo Canducci

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

  8. 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).

  9. 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.

  10. Strength of evidence relating periodontal disease and atherosclerotic disease.

    Science.gov (United States)

    Joshipura, Kaumudi; Zevallos, Juan Carlos; Ritchie, Christine Seel

    2009-09-01

    This review assesses the strength of evidence relating periodontal disease and atherosclerotic disease (ischemic heart disease, peripheral arterial disease, and ischemic stroke). Periodontal disease and atherosclerotic disease may be linked causally, or their relationship could be explained, wholly or partially, by common risk factors. Many potential pathways for the relationship have been postulated. This article focuses on evaluating the overall body of evidence, according to the following standard causal inference criteria: strength of association, dose-response relationship, time sequence, consistency, specificity, biologic plausibility, and independence from confounding. Each criterion is reviewed and evaluated against the existing literature. In summary, the overall strength of evidence for causal criteria for the relation between periodontal disease and atherosclerotic disease is as follows: The magnitude and consistency of the association is stronger for ischemic stroke (and is low for ischemic heart disease), some evidence for dose response exists, time sequence has been established with more evidence for stroke, and there is definitely biologic plausibility for all these associations. Independence from confounding is also stronger for ischemic stroke and peripheral arterial disease. Specificity is not established for any of these associations, as there are multiple risk factors for atherosclerotic disease; however, specificity is not considered an important criterion for causality. Because the underlying pathogenesis of atherosclerosis is common across the diseases, it is likely that if additional studies show consistent associations, periodontal disease may be an important independent causal risk factor for atherosclerotic disease, especially for ischemic stroke.

  11. 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.

  12. 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....../MS), as well as the combination of immobilized metal affinity chromatography methodology with matrix-assisted laser desorption/ionization MS/MS are described....... spectrometry (MS). Among the identified proteins, two isoforms of heat shock protein 27 (HSP27), a protein recently described as a potential biomarker of atherosclerosis, were detected. However, the putative mechanisms in which HSP27 isoforms could be involved in the atherosclerotic process are unknown. Thus...

  13. 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.

  14. Inflammatory Myopathies (Myositis)

    Science.gov (United States)

    ... Texas 2 Inflammatory Myopathies • ©2011 MDA Polymyositis and dermatomyositis mostly affect the muscles of the hips and ... matory myopathies in MDA’s program — polymyositis (PM) and dermatomyositis (DM) — effective treatments are avail- able. New research ...

  15. 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.

  16. Colitogenic role of tumour necrosis factor (TNF) receptors in trinitrobenzene sulphonic acid colitis: TNF-R1 ablation does not affect systemic inflammatory response.

    Science.gov (United States)

    Yang, Y; Wang, H; Dou, Y; Wang, Y; Han, G; Wang, Renxi; Wang, L; Guo, R; Xiao, H; Li, X; Shen, B; Shi, Y; Chen, G; Li, Y

    2011-09-01

    Tumour necrosis factor (TNF)-α plays a critical role in the pathogenesis of T helper type 1-mediated colitis such as Crohn's disease. However, the roles of its two receptors in mediating pathology remain largely unknown. In this study, trinitrobenzene sulphonic acid (TNBS) was used to induce colitis in TNF-receptor single or double knock-out (DKO) BALB/c mice and in wild-type counterparts. TNF-R1(-/-) mice had significantly less weight loss, reduced mortality, colon shortening and oedema, colon histological damage and lower levels of colon myeloperoxidase compared with wild-type (WT) BALB/c mice. A similar manifestation was also observed in TNF-R2(-/-) and TNF-R1(-/-) TNF-R2(-/-) (TNF-R DKO) mice. Strikingly, systemic inflammatory response (including splenomegaly and monocyte expansion) was found in WT and TNF-R1(-/-) mice after TNBS, instead of TNF-R2(-/-) and TNF-R DKO mice. Attenuated pathology of colitis in TNF-R1(-/-) or TNF-R2(-/-) mice correlated with lower amounts of interleukin (IL)-6, IL-1β, monocyte chemotactic protein (MCP)-1, IL-12p70 and interferon (IFN)-γ production in the colons. Importantly, ablation of TNF-R1 or TNF-R2 reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL)-positive apoptotic epithelial cells in the affected colons compared with WT TNBS-instilled controls, which might be due to the heightened ratio of Bcl-2/Bax and reduced activity of nuclear factor (NF)-κB. These findings suggest that either TNF-R1 or TNF-R2 plays a pathogenic role in the pathology of colitis and TNF signalling via TNF-R1 or TNF-R2 alone is not sufficient for inducing mucosal damage.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Qian Di

    2012-03-01

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

  20. Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression

    NARCIS (Netherlands)

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

    2015-01-01

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

  1. 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-

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

    Directory of Open Access Journals (Sweden)

    Helene Hartwig

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

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Pleunie van den Borne

    Full Text Available BACKGROUND: Leukotriene B4 (LTB4 has been associated with the initiation and progression of atherosclerosis and abdominal aortic aneurysm (AAA formation. However, associations of LTB4 levels with tissue characteristics and adverse clinical outcome of advanced atherosclerosis and AAA are scarcely studied. We hypothesized that LTB4 levels are associated with a vulnerable plaque phenotype and adverse clinical outcome. Furthermore, that LTB4 levels are associated with inflammatory AAA and adverse clinical outcome. METHODS: Atherosclerotic plaques and AAA specimens were selected from two independent databases for LTB4 measurements. Plaques were isolated during carotid endarterectomy from asymptomatic (n = 58 or symptomatic (n = 317 patients, classified prior to surgery. LTB4 levels were measured without prior lipid extraction and levels were corrected for protein content. LTB4 levels were related to plaque phenotype, baseline patient characteristics and clinical outcome within three years following surgery. Seven non-diseased mammary artery specimens served as controls. AAA specimens were isolated during open repair, classified as elective (n = 189, symptomatic (n = 29 or ruptured (n = 23. LTB4 levels were measured similar to the plaque measurements and were related to tissue characteristics, baseline patient characteristics and clinical outcome. Twenty-six non-diseased aortic specimens served as controls. RESULTS: LTB4 levels corrected for protein content were not significantly associated with histological characteristics specific for vulnerable plaques or inflammatory AAA as well as clinical presentation. Moreover, it could not predict secondary manifestations independently investigated in both databases. However, LTB4 levels were significantly lower in controls compared to plaque (p = 0.025 or AAA (p = 0.017. CONCLUSIONS: LTB4 levels were not associated with a vulnerable plaque phenotype or inflammatory AAA or clinical

  6. Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction

    Science.gov (United States)

    Joshi, Nikhil V; Toor, Iqbal; Shah, Anoop S V; Carruthers, Kathryn; Vesey, Alex T; Alam, Shirjel R; Sills, Andrew; Hoo, Teng Y; Melville, Adam J; Langlands, Sarah P; Jenkins, William S A; Uren, Neal G; Mills, Nicholas L; Fletcher, Alison M; van Beek, Edwin J R; Rudd, James H F; Fox, Keith A A; Dweck, Marc R; Newby, David E

    2015-01-01

    Background Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans. Methods and Results Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non–ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI. Conclusions The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254. PMID:26316523

  7. 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.

  8. Relation Between Circulating Inflammatory Chemokines and Vascular Characteristics in Healthy, Young Children

    NARCIS (Netherlands)

    Eikendal, Anouk L M; Evelein, Annemieke M V; Uiterwaal, Cuno S P M; van der Ent, Cornelis K; Visseren, Frank L J; Bots, Michiel L; Höfer, Imo E.; den Ruijter, Hester M; Dalmeijer, Geertje W

    2015-01-01

    BACKGROUND: Atherosclerosis begins in childhood with the occurrence of inflammatory vascular wall alterations that are detectable with B-mode ultrasound. Chemokines appear to be involved in the development of these alterations given that they occur early in the atherosclerotic pathway as mediators o

  9. 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.

  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. 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.)

  12. 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.

  13. Pathogen-mediated inflammatory atherosclerosis is mediated in part via Toll-like receptor 2-induced inflammatory responses.

    Science.gov (United States)

    Hayashi, Chie; Madrigal, Andres G; Liu, Xinyan; Ukai, Takashi; Goswami, Sulip; Gudino, Cynthia V; Gibson, Frank C; Genco, Caroline A

    2010-01-01

    Studies in humans have established that polymorphisms in genes encoding the innate immune Toll-like receptors (TLRs) are associated with inflammatory atherosclerosis. In hyperlipidemic mice, TLR2 and TLR4 have been reported to contribute to atherosclerosis progression. Human and mouse studies support a role for the oral pathogen Porphyromonas gingivalis in atherosclerosis, although the mechanisms by which this pathogen stimulates inflammatory atherosclerosis via innate immune system activation is not known. Using a genetically defined apolipoprotein E-deficient (ApoE(-/-)) mouse model we demonstrate that pathogen-mediated inflammatory atherosclerosis occurs via both TLR2-dependent and TLR2-independent mechanisms. P. gingivalis infection in mice possessing functional TLR2 induced the accumulation of macrophages as well as inflammatory mediators including CD40, IFN-gamma and the pro-inflammatory cytokines IL-1 beta, IL-6 and tumor necrosis factor-alpha in atherosclerotic lesions. The expression of these inflammatory mediators was reduced in atherosclerotic lesions from P. gingivalis-infected TLR2-deficient (TLR2(-/-)) mice. These studies provide a mechanistic link between an innate immune receptor and pathogen-accelerated atherosclerosis by a clinically and biologically relevant bacterial pathogen.

  14. Low- and high-dose plant and marine (n-3) fatty acids do not affect plasma inflammatory markers in adults with metabolic syndrome.

    Science.gov (United States)

    Dewell, Antonella; Marvasti, Farshad Fani; Harris, William S; Tsao, Philip; Gardner, Christopher D

    2011-12-01

    Chronic inflammation is considered to play a role in the development of cardiovascular disease. Various (n-3) fatty acids (FA) have been reported to have antiinflammatory effects, but there is a lack of consensus in this area, particularly in regard to optimal source(s) and dose(s). This study aimed to determine the effects of high and low doses of (n-3) FA from plant and marine sources on plasma inflammatory marker concentrations. One-hundred adults with metabolic syndrome were randomly assigned to a low or high dose of plant- (2.2 or 6.6 g/d α-linolenic acid) or marine- (1.2 or 3.6 g/d EPA and DHA) derived (n-3) FA or placebo for 8 wk, using a parallel arm design (n = 20/arm). Fasting blood samples collected at 0, 4, and 8 wk were analyzed for concentrations of monocyte chemotactic protein-1 (MCP-1), IL-6, and soluble intercellular adhesion molecule-1 (sICAM-1) and for cardiovascular risk factors. Baseline concentrations across all 5 groups combined were (mean ± SD) 103 ± 32 ng/L for MCP-1, 1.06 ± 0.56 ng/L for IL-6, and 0.197 ± 0.041 ng/L for sICAM-1. There were no significant differences in 8-wk changes in plasma inflammatory marker concentrations among the 5 groups. Plasma TG and blood pressure decreased significantly more and the LDL cholesterol concentration increased more in the high-dose fish oil group compared to the 8-wk changes in some of the other 4 groups (P ≤ 0.04). In conclusion, no beneficial effects were detected for any of the 3 inflammatory markers investigated in response to (n-3) FA in adults with metabolic syndrome regardless of dose or source.

  15. 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

  16. Delayed 18F-fluorodeoxyglucose PET/CT imaging improves quantitation of atherosclerotic plaque inflammation

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Thomassen, Anders; Takx, Richard A P

    2014-01-01

    BACKGROUND: This study aimed to determine if delayed (18)F-fluorodeoxyglucose ((18)FDG) PET/CT imaging improves quantitation of atherosclerotic plaque inflammation. Blood-pool activity can disturb the arterial (18)FDG signal. With time, blood-pool activity declines. Therefore, delayed imaging can...... potentially improve quantitation of vascular inflammation. METHODS AND RESULTS: 40 subjects were prospectively assessed by dual-time-point PET/CT imaging at approximately 90 and 180 minutes after (18)FDG administration. For both time-points, global uptake of (18)FDG was determined in the carotid arteries...... and thoracic aorta by calculating the blood-pool corrected maximum standardized uptake value (cSUVMAX). A target-to-background ratio (TBR) was calculated to determine the contrast resolution at 90 and 180 minutes. Furthermore, we assessed whether the acquisition time-point affected the relation between c...

  17. Inflammatory biomarkers for AMD.

    Science.gov (United States)

    Stanton, Chloe M; Wright, Alan F

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness worldwide, affecting an estimated 50 million individuals aged over 65 years.Environmental and genetic risk-factors implicate chronic inflammation in the etiology of AMD, contributing to the formation of drusen, retinal pigment epithelial cell dysfunction and photoreceptor cell death. Consistent with a role for chronic inflammation in AMD pathogenesis, several inflammatory mediators, including complement components, chemokines and cytokines, are elevated at both the local and systemic levels in AMD patients. These mediators have diverse roles in the alternative complement pathway, including recruitment of inflammatory cells, activation of the inflammasome, promotion of neovascularisation and in the resolution of inflammation. The utility of inflammatory biomarkers in assessing individual risk and progression of the disease is controversial. However, understanding the role of these inflammatory mediators in AMD onset, progression and response to treatment may increase our knowledge of disease pathogenesis and provide novel therapeutic options in the future.

  18. A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

    2014-01-01

    When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower...... suggest that cholesterol matrix formation may play a pathogenic role in atherosclerotic inflammation, and they indicate a mechanism by which bacteria and/or bacterial products may play a role in processes leading to arteriosclerosis....

  19. A tissue-engineered 3D model of light scattering in atherosclerotic plaques

    Science.gov (United States)

    Levitz, David; Hinds, Monica T.; Wang, Ruikang K.; Ma, Zhenhe; Ishii, Katsu; Tran, Noi; McCarty, Owen J. T.; Hanson, Stephen R.; Jacques, Steven L.

    2007-02-01

    The development of atherosclerotic plaques includes changes in the cellular and extracellular composition of the arterial wall. Although these changes in composition affect the manner in which light scatters in the vessel wall and thus affect any optical signal, experimentally determining how features of atherosclerosis affect optical signals has remained elusive. Using current tissue-engineering methods, we developed a 3D tissue construct model for assessing how certain features of atherosclerosis (the increased concentrations of lipids and macrophages) affect optical signals. The model is based on vascular tissue constructs made of smooth muscle cells (SMCs) and macrophages (M\\Fgr s) that are co-cultured inside a 3D scaffold matrix of collagen fibers with interspersed lipids. To make the scaffold matrix, powdered collagen was dissolved in acetic acid, homogenized, and neutralized by sequential dialyses to yield a soft gel of 2 μm thick collagen fibers in which cells were seeded. In "normal" constructs, only SMCs were seeded in the collagen gel; in "athero-like" constructs, both SMCs and M\\Fgr s (loaded or unloaded with lipid) were seeded in the gel. To demonstrate the use of this model, sets of slab-shaped normal and athero-like constructs were imaged by optical coherence tomography (OCT) and qualitatively analyzed. 2D frames from 3D OCT image cubes were compared to 2D histology sections. Our results indicate that the cellular composition of the construct affects morphological features of the OCT image.

  20. Escitalopram reduces circulating pro-inflammatory cytokines and improves depressive behavior without affecting sleep in a rat model of post-cardiac infarct depression.

    Science.gov (United States)

    Bah, Thierno Madjou; Benderdour, Mohamed; Kaloustian, Sévan; Karam, Ramy; Rousseau, Guy; Godbout, Roger

    2011-11-20

    Myocardial infarction (MI) in rats is followed by a behavioral syndrome similar to human post-MI depression. We tested the effects of escitalopram, a selective serotonin reuptake inhibitor, on this syndrome. MI was induced in 19 Sprague-Dawley rats by occluding the left anterior descending coronary artery for 40min, followed by reperfusion. A sham-operated group of 20 rats was submitted to the same protocol without coronary artery occlusion. Fifteen minutes after the onset of reperfusion, escitalopram (10mg/kg/day, i.p.) or saline was infused continuously through osmotic minipumps. After 2weeks of treatment, the rats were tested for behavioral despair and anhedonia by the forced swimming and sucrose preference tests, respectively. They were then sacrificed, and blood levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), PGE(2) and corticosterone were measured. In a separate cohort of 24 rats, sleep was recorded after 2weeks of post-MI treatment with escitalopram or saline. In MI rats, behavioral despair and anhedonia were blocked by escitalopram but prolonged sleep latency, low total sleep time and short latency to paradoxical sleep (PS) were not; escitalopram decreased PS in sham controls. Plasma TNF-α, PGE(2), and corticosterone levels were higher in MI rats than in the controls. Escitalopram lowered TNF-α, IL-1β, and PGE(2) levels in both groups of rats while IL-6 showed no differences whatsoever. Escitalopram reverses post-MI behavioral syndrome in rats through a mechanism that could involve a reduction of pro-inflammatory cytokines and PGE(2). It has limited effects on sleep disorders in MI rats but reduces PS in control rats.

  1. 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.

  2. Ets2 determines the inflammatory state of endothelial cells in advanced atherosclerotic lesions

    NARCIS (Netherlands)

    Cheng, C.Y.; Tempel, D.; den Dekker, W.K.; Haasdijk, R.; Chrifi, I.; Bos, F.L.; Wagtmans, K.; van de Kamp, E.H.; Blonden, L.; Biessen, E.A.; Moll, F.L.; Pasterkamp, G.; Serruys, P.W.; Schulte-Merker, S.; Duckers, H.J.

    2011-01-01

    RATIONALE: Neovascularization is required for embryonic development and plays a central role in diseases in adults. In atherosclerosis, the role of neovascularization remains to be elucidated. In a genome-wide microarray-screen of Flk1+ angioblasts during murine embryogenesis, the v-ets erythroblast

  3. Association between chlamydia pneumoniae infection and carotid atherosclerotic plaques

    Directory of Open Access Journals (Sweden)

    Fereshteh Ashtari

    2007-08-01

    Full Text Available BACKGROUND: Several studies have suggested an association between Chlamydia pneumonia infection and atherosclerosis. This study was designed to investigate the association between this organism and atherosclerotic plaque formation in right and left common carotid arteries (CCAs and extracranial portions of internal carotid arteries (ICAs.
    METHODS: Antibodies to Chlamydia pneumoniae (IgA and IgG were measured and compared in 42 patients who had plaque in at least one CCA or ICA (detected by duplex ultrasound and 82 patients without any plaque in these arteries. Cp.IgG and Cp.IgA titers over 1.10 ISR were defined to be positive.
    RESULTS: We found that 6.1% of control subjects and 16.7% of cases were Cp.IgA seropositive. The difference between these two groups was prominent but was not statistically significant (P = 0.104. 4.2% of females without atherosclerotic plaque and 31.6% of females with plaque were Cp.IgA seropositive. This difference is statistically significant (P = 0.005. There was no significant difference in seropositivity of Cp.IgG between case and control subjects or in male and female groups with or without plaque.
    CONCLUSIONS: Cp.IgA is a predictor of atherosclerosis in women, but Cp.IgG has no predictive value for plaque formation in either gender.
    KEY WORDS: Atherosclerotic plaque, Chlamydia pneumoniae, serum antibody.

  4. 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.

  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

    2016-10-04

    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.

  6. 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.......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...

  7. 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

  8. 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.

  9. Hexim1 heterozygosity stabilizes atherosclerotic plaque and decreased steatosis in ApoE null mice fed atherogenic diet.

    Science.gov (United States)

    Dhar-Mascareno, Manya; Rozenberg, Inna; Iqbal, Jahangir; Hussain, M Mahmood; Beckles, Daniel; Mascareno, Eduardo

    2017-02-01

    Hexim-1 is an inhibitor of RNA polymerase II transcription elongation. Decreased Hexim-1 expression in animal models of chronic diseases such as left ventricular hypertrophy, obesity and cancer triggered significant changes in adaptation and remodeling. The main aim of this study was to evaluate the role of Hexim1 in lipid metabolism focused in the progression of atherosclerosis and steatosis. We used the C57BL6 apolipoprotein E (ApoE null) crossed bred to C57BL6Hexim1 heterozygous mice to obtain ApoE null - Hexim1 heterozygous mice (ApoE-HT). Both ApoE null backgrounds were fed high fat diet for twelve weeks. Then, we evaluated lipid metabolism, atherosclerotic plaque formation and liver steatosis. In order to understand changes in the transcriptome of both backgrounds during the progression of steatosis, we performed Affymetrix mouse 430 2.0 microarray. After 12 weeks of HFD, ApoE null and ApoE-HT showed similar increase of cholesterol and triglycerides in plasma. Plaque composition was altered in ApoE-HT. Additionally, liver triglycerides and steatosis were decreased in ApoE-HT mice. Affymetrix analysis revealed that decreased steatosis might be due to impaired inducible SOCS3 expression in ApoE-HT mice. In conclusion, decreased Hexim-1 expression does not alter cholesterol metabolism in ApoE null background after HFD. However, it promotes stable atherosclerotic plaque and decreased steatosis by promoting the anti-inflammatory TGFβ pathway and blocking the expression of the inducible and pro-inflammatory expression of SOCS3 respectively.

  10. 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.

  11. Cervical Rotatory Manipulation Decreases Uniaxial Tensile Properties of Rabbit Atherosclerotic Internal Carotid Artery

    Science.gov (United States)

    Qi, Ji; Zhang, Lei; Chen, Chao; Mondal, Shubhro; Ping, Kaike; Chen, Yili

    2017-01-01

    Objective. To investigate the effects of one of the Chinese massage therapies, cervical rotatory manipulation (CRM), on uniaxial tensile properties of rabbit atherosclerotic internal carotid artery (ICA). Methods. 40 male purebred New Zealand white rabbits were randomly divided into CRM-Model group, Non-CRM-Model group, CRM-Normal group, and Non-CRM-Normal group. After modeling (atherosclerotic model) and intervention (CRM or Non-CRM), uniaxial tensile tests were performed on the ICAs to assess the differences in tensile mechanical properties between the four groups. Results. Both CRM and modeling were the main effects affecting physiological elastic modulus (PEM) of ICA. PEM in CRM-Model group was 1.81 times as much as Non-CRM-Model group, while the value in CRM-Model group was 1.34 times as much as CRM-Normal group. Maximum elastic modulus in CRM-Model group was 1.80 times as much as CRM-Normal group. Max strains in CRM-Model group and Non-CRM-Model group were 30.98% and 28.71% lower than CRM-Normal group and Non-CRM-Normal group, respectively. However, whether treated with CRM or not, the uniaxial tensile properties of healthy ICAs were not statistically different. Conclusion. CRM may decrease the uniaxial tensile properties of rabbit arteriosclerotic ICA, but with no effect on normal group. The study will aid in the meaningful explanation of the controversy about the harmfulness of CRM and the suitable population of CRM. PMID:28303160

  12. 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.

  13. Spectral characteristics of normal and atherosclerotic human coronary artery intima and media

    Science.gov (United States)

    Morcos, N. C.; Levy, Guy C.; Rizoiu, Ioana-Mihaela; Tomita, M.

    1994-07-01

    Efficient use and specific targeting of laser energy to atherosclerotic lesions necessitate understanding of spectral characteristics of intima and media from normal and diseased segments. We report absorption, transmission, and reflectance spectra from 19 normal and 21 diseased coronary artery segments which were obtained at autopsy within 5 to 10 h post mortem and submerged in oxygenated Ringer's solution. Spectra were obtained from the luminal surface of 1 X 1 cm full thickness arteries or bluntly dissected intima and media segments in the range 250 to 2500 nm. Water peaks were subtracted. Absorption and transmission for full thickness artery, intima, and media from normal and atherosclerotic arteries shared main bands at 1150 and 1700 nm with variation in intensity. Significant differences in reflectance showed bands at 1080, 1340, 1600, 1739 nm in normal intima and media and atherosclerotic intima but absent in media from atherosclerotic arteries. Peaks at 1340, 1600, and 1739 nm in normal intima and media are equalized in atherosclerotic intima and absent in atherosclerotic media. In conclusion, absence of reflectance at 1080, 1340, 1600, and 1739 nm in atherosclerotic media may be selectively utilized to target laser energy and ablation at intimal plaque and spare media of atherosclerotic arteries.

  14. Screening for chronic kidney disease can be of help to prevent atherosclerotic end organ damage

    NARCIS (Netherlands)

    Ozyilmaz, Akin; de Jong, Paul E.; Gansevoort, Ronald T.

    2012-01-01

    Atherosclerotic damage to the kidney is one of the most prevalent causes of chronic kidney disease and ultimately kidney failure. It frequently coincides with atherosclerotic damage to the heart, the brain and the lower extremities. In fact, the severity of the damage in the various end organs runs

  15. 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

  16. Effect of oral mineral and energy supplementation on blood mineral concentrations, energetic and inflammatory profile, and milk yield in dairy cows affected with dystocia.

    Science.gov (United States)

    Benzaquen, M; Galvão, K N; Coleman, A E; Santos, J E P; Goff, J P; Risco, C A

    2015-05-01

    The objectives of this study were to determine the effect of mineral/energy supplementation of dairy cows with dystocia on blood mineral concentrations, energetic and inflammatory profiles, and milk yield. Multiparous Holstein cows with dystocia were randomly assigned into two groups, (1) treated with a mineral/energy supplement (DME, n= 18) and (2) not treated (DNT, n= 22). A group of cows with normal parturition were randomly selected and were left untreated (NNT, n= 25). Cows in DME received an oral drench of 110 g of calcium and 400 g of propionate as calcium propionate plus 110 g potassium chloride and 150 g of magnesium sulfate administered within 6 h of calving and again 3 days post-partum. Compared to cows with a normal parturition, dystocic cows had decreased plasma calcium concentrations, increased plasma haptoglobin, decreased milk yield at 1 day post-partum, and tended to have increased rectal temperatures from 1 to 12 days post-partum. Compared with cows in DNT, those in DME had decreased plasma calcium concentrations and increased plasma magnesium concentrations 2 and 3 days post-partum, and a tendency for an increase in rectal temperature from 1 to 12 days post-partum. Dystocia is detrimental to calcium homeostasis post-partum, but mineral/energy supplementation as undertaken in this study is not recommended for use in cows with dystocia.

  17. 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

  18. The prevention and regression of atherosclerotic plaques: emerging treatments

    Directory of Open Access Journals (Sweden)

    Kalanuria AA

    2012-09-01

    Full Text Available Atul Ashok Kalanuria,1 Paul Nyquist,1 Geoffrey Ling1,21Division of Neuro Critical Care, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, 2Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, USAAbstract: Occlusive vascular diseases, such as sudden coronary syndromes, stroke, and peripheral arterial disease, are a huge burden on the health care systems of developed and developing countries. Tremendous advances have been made over the last few decades in the diagnosis and treatment of atherosclerotic diseases. Intravascular ultrasound has been able to provide detailed information of plaque anatomy and has been used in several studies to assess outcomes. The presence of atherosclerosis disrupts the normal protective mechanism provided by the endothelium and this mechanism has been implicated in the pathophysiology of coronary artery disease and stroke. Efforts are being put into the prevention of atherosclerosis, which has been shown to begin in childhood. This paper reviews the pathophysiology of atherosclerosis and discusses the current options available for the prevention and reversal of plaque formation.Keywords: cardiovascular, atherosclerotic disease, endothelium, plaque, reversal, coronary artery disease, stroke

  19. 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.

  20. 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.

  1. 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.

  2. Symptomatic Atherosclerotic Disease and Decreased Risk of Cancer-Specific Mortality

    Science.gov (United States)

    Benito-León, Julián; de la Aleja, Jesús González; Martínez-Salio, Antonio; Louis, Elan D.; Lichtman, Judith H.; Bermejo-Pareja, Félix

    2015-01-01

    Abstract The few studies that have assessed the association between symptomatic atherosclerotic disease and risk of cancer have had conflicting results. In addition, these studies ascertained participants either from treatment settings (ie, service-based studies) or by using a records linkage system (ie, medical records of patients evaluated at clinics or hospitals) and, therefore, were prone to selection bias. Our purpose was to estimate the risk of cancer mortality in a large population-based sample of elderly people, comparing participants with symptomatic atherosclerotic disease (atherosclerotic stroke and coronary disease) to their counterparts without symptomatic atherosclerotic disease (ie, controls) in the same population. In this population-based, prospective study (Neurological Disorders of Central Spain, NEDICES), 5262 elderly community-dwelling participants with and without symptomatic atherosclerotic disease were identified and followed for a median of 12.1 years, after which the death certificates of those who died were reviewed. A total of 2701 (53.3%) of 5262 participants died, including 314 (68.6%) of 458 participants with symptomatic atherosclerotic disease and 2387 (49.7%) of 4804 controls. Cancer mortality was reported significantly less often in those with symptomatic atherosclerotic disease (15.6%) than in controls (25.6%) (P < 0.001). In an unadjusted Cox model, risk of cancer-specific mortality was decreased in participants with symptomatic atherosclerotic disease (HR = 0.74, 95% confidence interval [CI], 0.55−0.98, P = 0.04) vs. those without symptomatic atherosclerotic disease (reference group). In an adjusted Cox model, HR = 0.58; 95% CI, 0.38−0.89; P = 0.01. This population-based, prospective study suggests that there is an inverse association between symptomatic atherosclerotic disease and risk of cancer mortality. PMID:26266364

  3. Evolution of inflammatory diseases.

    Science.gov (United States)

    Okin, Daniel; Medzhitov, Ruslan

    2012-09-11

    The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental trade-off between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple trade-offs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases.

  4. [Inflammatory myopathies].

    Science.gov (United States)

    Maurer, Britta

    2017-02-01

    Inflammatory myopathies comprise heterogeneous, often multisystemic autoimmune diseases with muscle involvement as a common feature. The prognosis largely depends on a timely diagnosis and initiation of therapy. Given the complexity of these rare diseases, when an inflammatory myopathy is suspected patients should be referred to an expert center with established algorithms for the diagnostic work-up. The differential diagnostic exclusion of myositis mimics should ideally be carried out in close collaboration with neurologists and neuropathologists. The choice of immunosuppressive treatment should primarily depend on disease severity and organ involvement but age and comorbidities also have to be taken into account.

  5. Aging negatively skews macrophage TLR2- and TLR4-mediated pro-inflammatory responses without affecting the IL-2-stimulated pathway.

    Science.gov (United States)

    Boehmer, Eric D; Meehan, Michael J; Cutro, Brent T; Kovacs, Elizabeth J

    2005-12-01

    We recently reported that macrophages from aged mice produced less tumor necrosis factor (TNF)-alpha following lipopolysaccharide (LPS) stimulation than macrophages from young animals. This correlated with decreased levels of phosphorylated and total p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs). Here, we went on to determine if age affects other Toll-like (TLR) and non-TLR signaling pathways. We found that LPS- and zymosan-stimulated TNF-alpha and IL-6 production is attenuated in splenic macrophages from aged mice compared to young. Conversely, LPS-stimulated, but not zymosan-stimulated, IL-10 production from the aged group was elevated over that of the young group. In contrast, IL-2-stimulated TNF-alpha and IL-6 production was not affected by age. The age-associated changes did not correlate with alterations in the cell-surface expression of TLR2, TLR4, or IL-2Rbeta. Macrophages from aged mice demonstrated lower p38 MAPK and MAPK-activated protein kinase (APK)-2 activation. Protein expression of p38, but not MAPK-APK-2, was reduced with age. Additionally, nuclear factor (NF)-kappaB activation was significantly decreased in macrophages from aged mice after exposure to LPS, but not IL-2. These data indicate that age-associated macrophage signaling alterations are pathway-specific and suggest that TLR-mediated pathways are impaired with age at the level of MAPK expression.

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

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

    . An increase of 30% in the axial width and 10% in the lateral width of the PSF was found, thus, the point resolution capability is only reduced marginally. Visualization of tissue interfaces was investigated using rubber tube phantoms, porcine aorta, and human plaque specimens. The MACI images show improved...... 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...... reflectors and the correspondence was found to be high for reflectors near the acoustical axis of the transducer and moderate for reflectors far off-axis.An ultrasound imaging modality, Multi-Angle Compound Imaging (MACI), has been developed for imaging of vascular structures and investigated theoretically...

  7. 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.

  8. 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.

  9. Effect of hyperlipidemia on the expression of circadian genes in apolipoprotein E knock-out atherosclerotic mice

    Directory of Open Access Journals (Sweden)

    Chen Sifeng

    2009-12-01

    Full Text Available Abstract Background Circadian patterns of cardiovascular vulnerability were well characterized, with a peak incidence of acute myocardial infarction and stroke secondary to atherosclerosis in the morning, which showed the circadian clock may take part in the pathological process of atherosclerosis induced by hyperlipidemia. Hence, the effect of hyperlipidemia on the expression of circadian genes was investigated in atherosclerotic mouse model. Results In apoE-/-mice on regular chow or high-fat diet, an atherosclerotic mouse model induced by heperlipidemia, we found that the peak concentration of serum lipids was showed four or eight hours later in apoE-/- mice, compared to C57BL/6J mice. During the artificial light period, a reduce in circulating level of serum lipids corresponded with the observed increase of the expression levels of some the transcription factors involved in lipid metabolism, such as PPARα and RXRα. Meanwhile, the expression of circadian genes was changed following with amplitude reduced or the peak mRNA level delayed. Conclusions Our studies indicated that heperlipidemia altered both the rhythmicity and expression of circadian genes. Diet-induced circadian disruption may affect the process of atherosclerosis and some acute cardiovascular disease.

  10. Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p

    Energy Technology Data Exchange (ETDEWEB)

    Broisat, A.; Riou, L.M.; Ardisson, V.; Fagret, D.; Ghezzi, C. [INSERM, U340, Radiopharmaceutiques Biocliniques, La Tronche (France); Universite de Grenoble, Saint Martin d' Heres (France); Boturyn, D.; Dumy, P. [Universite de Grenoble, Saint Martin d' Heres (France); LEDSS V - Ingenierie Moleculaire, CNRS UMR 5616, Saint Martin d' Heres (France)

    2007-06-15

    VCAM-1 plays a major role in the chronic inflammatory processes present in vulnerable atherosclerotic plaques. The residues 75-84 (B2702-p) and 84-75/75-84 (B2702-rp) of the major histocompatibility complex-1 (MHC-1) molecule B2702 were previously shown to bind specifically to VCAM-1. We hypothesised that radiolabelled B2702-p and B2702-rp might have potential for the molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) expression in atherosclerotic plaques. Preliminary biodistribution studies indicated that {sup 125}I-B2702-rp was unsuitable for in vivo imaging owing to extremely high lung uptake. {sup 123}I- or {sup 99m}Tc-labelled B2702-p was injected intravenously to Watanabe heritable hyperlipidaemic rabbits (WHHL, n = 6) and control animals (n = 6). After 180 min, aortas were harvested for ex vivo autoradiographic imaging, gamma-well counting, VCAM-1 immunohistology and Sudan IV lipid staining. Robust VCAM-1 immunostaining was observed in Sudan IV-positive and to a lesser extent in Sudan IV-negative areas of WHHL animals, whereas no expression was detected in control animals. Significant 2.9-fold and 1.9-fold increases in {sup 123}I-B2702-p and {sup 99m}Tc-B2702-p aortic-to-blood ratios, respectively, were observed between WHHL and control animals (p < 0.05). Tracer uptake on ex vivo images co-localised with atherosclerotic plaques. Image quantification indicated a graded increase in {sup 123}I-B2702-p and {sup 99m}Tc-B2702-p activities from control to Sudan IV-negative and to Sudan IV-positive areas, consistent with the observed pattern of VCAM-1 expression. Sudan IV-positive to control area tracer activity ratios were 17.0 {+-} 9.0 and 5.9 {+-} 1.8 for {sup 123}I-B2702-p and {sup 99m}Tc-B2702-p, respectively. Radiolabelled B2702-p is a potentially useful radiotracer for the molecular imaging of VCAM-1 in atherosclerosis. (orig.)

  11. The F11 receptor (F11R/JAM-A) in atherothrombosis: overexpression of F11R in atherosclerotic plaques.

    Science.gov (United States)

    Babinska, Anna; Azari, Bani M; Salifu, Moro O; Liu, Ruijie; Jiang, Xian-Cheng; Sobocka, Malgorzata B; Boo, Dorothy; Al Khoury, George; Deitch, Jonathan S; Marmur, Jonathan D; Ehrlich, Yigal H; Kornecki, Elizabeth

    2007-02-01

    F11R is the gene name for an adhesion protein, called the F11-receptor, aka JAM-A, which under normal physiological conditions is expressed constitutively on the surface of platelets and localized within tight junctions of endothelial cells (EC). Previous studies of the interactions between human platelets and EC suggested that F11R/JAM-A plays a crucial role in inflammatory thrombosis and atherosclerosis. The study reported here obtained in-vivo confirmation of this conclusion by investigating F11R/JAM-A protein and mRNA in patients with aortic and peripheral vascular disease and in an animal model of atherosclerosis. Molecular and immunofluorescence determinations revealed very high levels of F11R/JAM-A mRNA and F11R/JAM-A protein in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with 12-week-old atherosclerosis-prone apoE-/- mice, an age in which atherosclerotic plaques are well established. Enhanced expression of the F11R/JAM-A message in cultured EC from human aortic and venous vessels was observed following exposure of the cells to cytokines. Determinations of platelet adhesion to cultured EC inflamed by combined cytokine treatment in the presence of F11R/JAM-A - antagonists provided data indicating that de novo expression of F11R/JAM-A on the luminal surface of inflamed EC has an important role in the conversion of EC to a thrombogenic surface. Further studies of these interactions under flow conditions and under in-vivo settings could provide a final proof of a causal role for F11R/JAM-A in the initiation of thrombosis. Based on our in-vitro and in-vivo studies to date, we propose that therapeutic drugs which antagonize the function of F11R/JAM-A should be tested as novel means for the prevention and treatment of atherosclerosis, heart attacks and stroke.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Characterization of atherosclerotic plaque-depositions by infrared, Raman and CARS microscopy

    Science.gov (United States)

    Matthäus, Christian; Bergner, Gero; Krafft, Christoph; Dietzek, Benjamin; Romeike, Bernd F. M.; Brehm, Bernhard R.; Popp, Jürgen

    2011-07-01

    Atherosclerotic plaques are mainly composed of proteoglycans, triglycerides, cholesterol, cholesterolester and crystalline calcium. From histopathological characterizations it is known that the composition of these atherosclerotic plaques can vary to a great extent, due to different risk factors as smoking, hyperlipedemia, or genetic background ect. The individual plaque components can be spectroscopically easily identified. Furthermore, spectroscopic imaging technologies offer the possibility to study the plaque compositions in a more quantitative manner than traditional staining techniques. Here, we compare the potential of IR, Raman and CARS microscopy to characterize the constitution of atherosclerotic plaques as well as the structure of the surrounding tissue. For data analysis and image reconstruction spectral decomposition algorithms such as vertex component analysis (VCA) were introduced. The results are in good agreement with the histopathology. Aim of the study is to correlate the compositional characteristics of atherosclerotic plaques with individual disease patterns.

  17. 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.

  18. Aggregatibacter actinomycetemcomitans induces Th17 cells in atherosclerotic lesions.

    Science.gov (United States)

    Jia, Ru; Hashizume-Takizawa, Tomomi; Du, Yuan; Yamamoto, Masafumi; Kurita-Ochiai, Tomoko

    2015-04-01

    Th17 cells have been linked to the pathogenesis of several chronic inflammatory and autoimmune diseases. However, the role of Th17 cells and IL-17 in atherosclerosis remains poorly understood. We previously reported that Aggregatibacter actinomycetemcomitans (Aa) bacteremia accelerated atherosclerosis accompanied by inflammation in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice. In this study, we investigated whether Aa promotes the Th17 inducing pathway in Aa-challenged Apoe(shl) mice. Mice were intravenously injected with live Aa HK1651 or vehicles. Time-course analysis of splenic IL-17(+)CD4(+) cell frequencies, the proximal aorta lesion area, serum IL-17, IL-6, TGF-β and IL-1β levels, the mRNA expression of Th17-related molecules such as IL-1β, IL-6, IL17RA, STAT3, IL-21, IL-23, TGF-β and RORγt, Th17-related microRNA levels and the levels of AIM-2, Mincle and NLRP3 were examined. Challenge with Aa time dependently induced tropism of Th17 cells in the spleen and increase in atheromatous lesions in the aortic sinus of Apoe(shl) mice. Serum IL-17, IL-6, TGF-β and IL-1β levels were significantly enhanced by Aa. The gene expression of IL-1β, IL-6, IL-17RA, IL-21, IL-23, TGF-β, STAT3, RORγt, AIM-2, Mincle and NLRP3 was also time dependently stimulated in the aorta of Aa-challenged mice. Furthermore, Aa challenge significantly increased the expression of miR-146b and miR-155 in the aorta. Based on the results, it seems that Aa stimulates Th17 induction that affects the progression of Aa-accelerated atherosclerosis.

  19. 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....

  20. Moderate overweight is beneficial and severe obesity detrimental for patients with documented atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Azimi, Aziza; Charlot, Mette Gitz; Torp-Pedersen, Christian Tobias

    2013-01-01

    Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease.......Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease....

  1. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-15

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

  3. 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.

  4. 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 aortic 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.

  5. 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

  6. Irradiation induces different inflammatory and thrombotic responses in carotid arteries of wildtype C57BL/6J and atherosclerosis-prone ApoE(-/-) mice

    NARCIS (Netherlands)

    Hoving, S.; Heeneman, S.; Gijbels, M.J.J.; Te Poele, J.A.; Visser, N.; Cleutjens, J.; Russell, N.S.; Daemen, M.J.; Stewart, F.A.

    2012-01-01

    BACKGROUND AND PURPOSE: We have previously shown that irradiation to the carotid arteries of hypercholesterolemic ApoE(-/-) mice accelerated the development of macrophage-rich, inflammatory atherosclerotic lesions. We now investigated the mechanism underlying the development of radiation-induced ath

  7. Emergency EC-IC bypass for symptomatic atherosclerotic ischemic stroke.

    Science.gov (United States)

    Horiuchi, Tetsuyoshi; Nitta, Junpei; Ishizaka, Shigetoshi; Kanaya, Kohei; Yanagawa, Takao; Hongo, Kazuhiro

    2013-10-01

    Previous studies have shown that extracranial-intracranial (EC-IC) bypass surgery has no preventive effect on subsequent ipsilateral ischemic stroke in patients with symptomatic atherosclerotic internal carotid occlusion and hemodynamic cerebral ischemia. A few studies have assessed whether an urgent EC-IC bypass surgery is an effective treatment for main trunk stenosis or occlusion in acute stage. The authors retrospectively reviewed 58 consecutive patients who underwent urgent EC-IC bypass for symptomatic internal carotid artery or the middle cerebral artery stenosis or occlusion between January 2003 and December 2011. Clinical characteristics and neuroimagings were evaluated and analyzed. Based on preoperative angiogram, responsible lesions were the internal carotid artery in 19 (32.8%) patients and the middle cerebral artery in 39 (67.2%). No hemorrhagic complication occurred. Sixty-nine percent of patients showed improvement of neurological function after surgery, and 74.1% of patients had favorable outcome. Unfavorable outcome was associated with insufficient collateral flow and new infarction after bypass surgery.

  8. 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.

  9. Multimodal spectroscopy detects features of vulnerable atherosclerotic plaque

    Science.gov (United States)

    Šćepanović, Obrad R.; Fitzmaurice, Maryann; Miller, Arnold; Kong, Chae-Ryon; Volynskaya, Zoya; Dasari, Ramachandra R.; Kramer, John R.; Feld, Michael S.

    2011-01-01

    Early detection and treatment of rupture-prone vulnerable atherosclerotic plaques is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy-termed multimodal spectroscopy (MMS)-provides detailed biochemical information about tissue and can detect vulnerable plaque features: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), and thrombus. Ex vivo MMS spectra are collected from 12 patients that underwent carotid endarterectomy or femoral bypass surgery. Data are collected by means of a unitary MMS optical fiber probe and a portable clinical instrument. Blinded histopathological analysis is used to assess the vulnerability of each spectrally evaluated artery lesion. Modeling of the ex vivo MMS spectra produce objective parameters that correlate with the presence of vulnerable plaque features: TFC with fluorescence parameters indicative of collagen presence; NC/SFC with a combination of diffuse reflectance β-carotene/ceroid absorption and the Raman spectral signature of lipids; and thrombus with its Raman signature. Using these parameters, suspected vulnerable plaques can be detected with a sensitivity of 96% and specificity of 72%. These encouraging results warrant the continued development of MMS as a catheter-based clinical diagnostic technique for early detection of vulnerable plaques.

  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. Polymorphisms in the interleukin-10 gene and chronic periodontitis in patients with atherosclerotic and aortic aneurysmal vascular diseases

    Directory of Open Access Journals (Sweden)

    Zahra Armingohar

    2015-02-01

    Full Text Available Background: Chronic periodontitis (CP, atherosclerotic and aortic aneurysmal vascular diseases (VD are chronic inflammatory conditions with multifactorial etiologies, including involvement of predisposing genetic factors. In a previous study, polymorphisms in the gene for the anti-inflammatory interleukin-1 receptor antagonist were associated with CP in patients with VD. Objective: This study investigates whether polymorphisms in the gene for the anti-inflammatory interleukin-10 (IL10 could be related to CP in the same manner. Methods: Seventy-two patients with VD of whom 35 had CP were genotyped for single nucleotide polymorphisms (SNPs in the IL10 −592 (rs1800872, −819 (rs1800871, and −1,082 (rs1800896 gene by Taqman rtPCR method and by DNA sequencing. Results: The C alleles and C/C genotypes of IL10 −592 and IL10 −819 frequencies were significantly higher, while the frequencies of the IL10 −592 (C/A and IL10 −819 (C/T heterozygote genotypes were significantly lower in the VD group with CP compared to those without CP. The IL10 haplotype ATA frequency (−1,082, −819, −592 showed a trend to a significant difference between the two groups indicating protection against CP. Conclusions: Taken together, our findings suggest an independent association of genetic polymorphisms in the IL-10 gene locus with CP in patients with VD. Development of CP and the implications on vascular disease emphasize the importance of early detection and adequate treatment of periodontitis among these patients.

  12. Atherosclerotic Plaque Stability Is Affected by the Chemokine CXCL10 in Both Mice and Humans

    Directory of Open Access Journals (Sweden)

    Dolf Segers

    2011-01-01

    Full Text Available Background. The chemokine CXCL10 is specifically upregulated during experimental development of plaque with an unstable phenotype. In this study we evaluated the functional consequences of these findings in mice and humans. Methods and Results. In ApoE-/- mice, we induced unstable plaque with using a flow-altering device around the carotid artery. From week 1 to 4, mice were injected with a neutralizing CXCL10 antibody. After 9 weeks, CXCL10 inhibition resulted in a more stable plaque phenotype: collagen increased by 58% (P=0.002, smooth muscle cell content increased 2-fold (P=0.03, while macrophage MHC class II expression decreased by 50% (P=0.005. Also, the size of necrotic cores decreased by 41% (P=0.01. In 106 human carotid endarterectomy specimens we found that increasing concentrations of CXCL10 strongly associate with an increase in atheromatous plaque phenotype (ANOVA, P=0.003, with high macrophage, low smooth muscle cell, and low collagen content. Conclusions. In the present study we showed that CXCL10 is associated with the development of vulnerable plaque in human and mice. We conclude that CXCL10 might provide a new lead towards plaque-stabilizing therapy.

  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. Fiber-optic system for dual-modality imaging of glucose probes 18F-FDG and 6-NBDG in atherosclerotic plaques.

    Directory of Open Access Journals (Sweden)

    Raiyan T Zaman

    Full Text Available Atherosclerosis is a progressive inflammatory condition that underlies coronary artery disease (CAD-the leading cause of death in the United States. Thus, the ultimate goal of this research is to advance our understanding of human CAD by improving the characterization of metabolically active vulnerable plaques within the coronary arteries using a novel catheter-based imaging system. The aims of this study include (1 developing a novel fiber-optic imaging system with a scintillator to detect both 18F and fluorescent glucose probes, and (2 validating the system on ex vivo murine plaques.A novel design implements a flexible fiber-optic catheter consisting of both a radio-luminescence and a fluorescence imaging system to detect radionuclide 18F-fluorodeoxyglucose (18F-FDG and the fluorescent analog 6-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-ylamino-6-Deoxyglucose (6-NBDG, respectively. Murine macrophage-rich atherosclerotic carotid plaques were imaged ex vivo after intravenous delivery of 18F-FDG or 6-NBDG. Confirmatory optical imaging by IVIS-200 and autoradiography were also performed.Our fiber-optic imaging system successfully visualized both 18F-FDG and 6-NBDG probes in atherosclerotic plaques. For 18F-FDG, the ligated left carotid arteries (LCs exhibited 4.9-fold higher radioluminescence signal intensity compared to the non-ligated right carotid arteries (RCs (2.6 × 10(4 ± 1.4 × 10(3 vs. 5.4 × 10(3 ± 1.3 × 10(3 A.U., P = 0.008. Similarly, for 6-NBDG, the ligated LCs emitted 4.3-fold brighter fluorescent signals than the control RCs (1.6 × 10(2 ± 2.7 × 10(1 vs. 3.8 × 10(1 ± 5.9 A.U., P = 0.002. The higher uptake of both 18F-FDG and 6-NBDG in ligated LCs were confirmed with the IVIS-200 system. Autoradiography further verified the higher uptake of 18F-FDG by the LCs.This novel fiber-optic imaging system was sensitive to both radionuclide and fluorescent glucose probes taken up by murine atherosclerotic plaques. In addition, 6-NBDG is a

  15. 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

  16. 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 (pcollagen type I distal to the bifurcation compared to proximal tissue in the carotid specimens. Conclusion: Fluorescence spectroscopy

  17. Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo.

    Science.gov (United States)

    Maraloiu, Valentin-Adrian; Appaix, Florence; Broisat, Alexis; Le Guellec, Dominique; Teodorescu, Valentin Serban; Ghezzi, Catherine; van der Sanden, Boudewijn; Blanchin, Marie-Genevieve

    2016-01-01

    The storage and catabolism of Ultrasmall SuperParamagnetic Iron Oxide (USPIO) nanoparticles were analyzed through a multiscale approach combining Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM) at different times after intravenous injection in an atherosclerotic ApoE(-/-) mouse model. The atherosclerotic plaque features and the USPIO heterogeneous biodistribution were revealed down from organ's scale to subcellular level. The biotransformation of the nanoparticle iron oxide (maghemite) core into ferritin, the non-toxic form of iron storage, was demonstrated for the first time ex vivo in atherosclerotic plaques as well as in spleen, the iron storage organ. These results rely on an innovative spatial and structural investigation of USPIO's catabolism in cellular phagolysosomes. This study showed that these nanoparticles were stored as non-toxic iron compounds: maghemite oxide or ferritin, which is promising for MRI detection of atherosclerotic plaques in clinics using these USPIOs. From the Clinical Editor: Advance in nanotechnology has brought new contrast agents for clinical imaging. In this article, the authors investigated the use and biotransformation of Ultrasmall Super-paramagnetic Iron Oxide (USPIO) nanoparticles for analysis of atherosclerotic plagues in Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM). The biophysical data generated from this study could enable the possible use of these nanoparticles for the benefits of clinical patients.

  18. 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 ...

  19. 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.

  20. [The effect of carotid endarterectomy on cognitive disturbances in patients with atherosclerotic stenosis of carotid arteries].

    Science.gov (United States)

    Iakhno, N N; Fedorova, T S; Damulin, I V; Shcherbiuk, A N; Vinogradov, O A; Lavrent'ev, A V

    2011-01-01

    Clinical and neuropsychological features of non-dementia cognitive disturbances were studied in 102 patients with atherosclerotic carotid stenosis. Cognitive disturbances were assessed after the carotid endarterectomy (CEAE). Mild cognitive impairment was found in 37 (36,3%) of patients, moderate cognitive impairment was diagnosed in 36 (35,3%)patients. Moderate cognitive impairment was found more often in patients with symptomatic carotid stenosis with structural brain changes confirmed by neuroimaging data and with instable atherosclerotic plaques with the predomination of hypodensity component. It allows to suggest that both the reduction of perfusion and arterio-arterial microemboli may cause cognitive dysfunction in patients with atherosclerotic carotid stenosis. The data on the positive effect of CEAE on cognitive functions have been obtained. The positive changes were more distinct in patients with asymptomatic course of carotid stenosis. However CEAE may have a negative effect on cognitive functions in patients with moderate cognitive impairment of dysmnestic character and symptomatic carotid stenosis.

  1. 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.

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

    Science.gov (United States)

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

    2016-03-01

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

  3. 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

    2015-01-01

    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 zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked. PMID:26752654

  4. 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

  5. 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.

  6. 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.

  7. Coding Microsatellite Frameshift Mutations Accumulate in Atherosclerotic Carotid Artery Lesions: Evaluation of 26 Cases and Literature Review.

    Science.gov (United States)

    Kurz, Carolin; Hakimi, Maani; Kloor, Matthias; Grond-Ginsbach, Caspar; Gross-Weissmann, Marie-Luise; Böckler, Dittmar; von Knebel Doeberitz, Magnus; Dihlmann, Susanne

    2015-06-09

    Somatic DNA alterations are known to occur in atherosclerotic carotid artery lesions; however, their significance is unknown. The accumulation of microsatellite mutations in coding DNA regions may reflect a deficiency of the DNA mismatch repair (MMR) system. Alternatively, accumulation of these coding microsatellite mutations may indicate that they contribute to the pathology. To discriminate between these two possibilities, we compared the mutation frequencies in coding microsatellites (likely functionally relevant) with those in noncoding microsatellites (likely neutral). Genomic DNA was isolated from carotid endarterectomy (CEA) specimens of 26 patients undergoing carotid surgery and from 15 nonatherosclerotic control arteries. Samples were analyzed by DNA fragment analysis for instability at three noncoding (BAT25, BAT26, CAT25) and five coding (AIM2, ACVR2, BAX, CASP5, TGFBR2) microsatellite loci, with proven validity for detection of microsatellite instability in neoplasms. We found an increased frequency of coding microsatellite mutations in CEA specimens compared with control specimens (34.6 versus 0%; p = 0.0013). Five CEA specimens exhibited more than one frameshift mutation, and ACVR2 and CASP5 were affected most frequently (5/26 and 6/26). Moreover, the rate of coding microsatellite alterations (15/130) differed significantly from that of noncoding alterations (0/78) in CEA specimens (p = 0.0013). In control arteries, no microsatellite alterations were observed, neither in coding nor in noncoding microsatellite loci. In conclusion, the specific accumulation of coding mutations suggests that these mutations play a role in the pathogenesis of atherosclerotic carotid lesions, since the absence of mutations in noncoding microsatellites argues against general microsatellite instability, reflecting MMR deficiency.

  8. 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.

  9. 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

  10. 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...

  11. Automated segmentation of atherosclerotic histology based on pattern classification

    Directory of Open Access Journals (Sweden)

    Arna van Engelen

    2013-01-01

    Full Text Available Background: Histology sections provide accurate information on atherosclerotic plaque composition, and are used in various applications. To our knowledge, no automated systems for plaque component segmentation in histology sections currently exist. Materials and Methods: We perform pixel-wise classification of fibrous, lipid, and necrotic tissue in Elastica Von Gieson-stained histology sections, using features based on color channel intensity and local image texture and structure. We compare an approach where we train on independent data to an approach where we train on one or two sections per specimen in order to segment the remaining sections. We evaluate the results on segmentation accuracy in histology, and we use the obtained histology segmentations to train plaque component classification methods in ex vivo Magnetic resonance imaging (MRI and in vivo MRI and computed tomography (CT. Results: In leave-one-specimen-out experiments on 176 histology slices of 13 plaques, a pixel-wise accuracy of 75.7 ± 6.8% was obtained. This increased to 77.6 ± 6.5% when two manually annotated slices of the specimen to be segmented were used for training. Rank correlations of relative component volumes with manually annotated volumes were high in this situation (P = 0.82-0.98. Using the obtained histology segmentations to train plaque component classification methods in ex vivo MRI and in vivo MRI and CT resulted in similar image segmentations for training on the automated histology segmentations as for training on a fully manual ground truth. The size of the lipid-rich necrotic core was significantly smaller when training on fully automated histology segmentations than when manually annotated histology sections were used. This difference was reduced and not statistically significant when one or two slices per section were manually annotated for histology segmentation. Conclusions: Good histology segmentations can be obtained by automated segmentation

  12. 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.

  13. 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.

  14. 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.

  15. Positron emission tomography of the vulnerable atherosclerotic plaque in man--a contemporary review

    DEFF Research Database (Denmark)

    Pedersen, Sune F; Hag, Anne Mette F; Klausen, Thomas L;

    2014-01-01

    of cellular and subcellular physiological processes as they take place in vivo; using this technology we can obtain valuable information on atherosclerostic plaque composition. Applying molecular imaging clinically to atherosclerotic disease therefore has the potential to identify atherosclerotic plaques...... vulnerable to rupture. This could prove to be an important tool for the selection of patients for CEA surgery in a health system increasingly focused on individualized treatment. This review focuses on current advances and future developments of in vivo atherosclerosis PET imaging in man....

  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. 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.

  18. Atherosclerotic ischemic renal disease. Diagnosis and prevalence in an hypertensive and/or uremic elderly population

    Directory of Open Access Journals (Sweden)

    Rossi Michele

    2003-02-01

    Full Text Available Abstract Background Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure leading to dialysis among the elderly; Its prevalence is inferred from autopsy or retrospective arteriographic studies. This study has been conducted on 269 subjects over 50 with hypertension and/or CRF, unrelated to other known causes of renal disease. Methods All 269 patients were studied either by color-flow duplex sonography (n = 238 or by renal scintigraphy (n = 224, and 199 of the 269 patients were evaluated using both of these techniques. 40 patients, found to have renal artery stenosis (RAS, were subjected to 3D-contrast enhancement Magnetic Resonance Angiography (MRA and/or Selective Angiography (SA. An additional 23 cases, negative both to scintigraphy and to ultrasound study, underwent renal angiography (MRA and/or SA. Results Color-duplex sonography, carried out in 238 patients, revealed 49 cases of RAS. MR or SA was carried out in 35 of these 49 patients, and confirmed the diagnosis in 33. Color-duplex sonography showed a PPV value of 94.3% and NPV of 87.0% while renal scintigraphy, carried out in 224 patients, had a PPV of 72.2% and a NPV of 29.4%. Patients with RAS showed a higher degree of renal insufficiency compared to non stenotic patients while there were no differences in proteinuria. RAS, based on color-duplex sonography studies, was present in 11% of patients in the age group 50–59, 18% in the 60–69 and 23% at age 70 and above. Conclusions A relatively large percentage of the elderly population with renal insufficiency and/or hypertension is affected by RAS and is at risk of developing end-stage renal failure. Color-duplex ultrasonography is a valid routine method of investigation of population at risk for renal artery stenosis.

  19. 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.

  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. Myeloid dendritic cells: Development, functions, and role in atherosclerotic inflammation.

    Science.gov (United States)

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

    2015-06-01

    Myeloid dendritic cells (mDCs) comprise a heterogeneous population of professional antigen-presenting cells, which are responsible for capture, processing, and presentation of antigens on their surface to T cells. mDCs serve as a bridge linking adaptive and innate immune responses. To date, the development of DC lineage in bone marrow is better characterized in mice than in humans. DCs and macrophages share the common myeloid progenitor called macrophage-dendritic cell progenitor (MDP) that gives rise to monocytoid lineage and common DC progenitors (CDPs). CDP in turn gives rise to plasmacytoid DCs and predendritic cells (pre-mDCs) that are common precursor of myeloid CD11b+ and CD8α(+) DCs. The development and commitment of mDCs is regulated by several transcription and hematopoietic growth factors of which CCr7, Zbtb46, and Flt3 represent 'core' genes responsible for development and functional and phenotypic maintenance of mDCs. mDCs were shown to be involved in the pathogenesis of many autoimmune and inflammatory diseases including atherosclerosis. In atherogenesis, different subsets of mDCs could possess both proatherogenic (e.g. proinflammatory) and atheroprotective (e.g. anti-inflammatory and tolerogenic) activities. The proinflammatory role of mDCs is consisted in production of inflammatory molecules and priming proinflammatory subsets of effector T cells. In contrast, tolerogenic mDCs fight against inflammation through arrest of activity of proinflammatory T cells and macrophages and induction of immunosuppressive regulatory T cells. Microenvironmental conditions trigger differentiation of mDCs to acquire proinflammatory or regulatory properties.

  2. 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.

  3. 64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVE: A feature of vulnerable atherosclerotic plaques of the carotid artery is high activity and abundance of lesion macrophages. There is consensus that this is of importance for plaque vulnerability, which may lead to clinical events, such as stroke and transient ischemic attack. We used p...

  4. 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.

  5. 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...

  6. Fast and Accurate Pressure-Drop Prediction in Straightened Atherosclerotic Coronary Arteries

    NARCIS (Netherlands)

    J.T.C. Schrauwen (Jelle); D. Koeze (Dion); J.J. Wentzel (Jolanda); F.N. van de Vosse (Frans); A.F.W. van der Steen (Ton); F.J.H. Gijsen (Frank)

    2014-01-01

    textabstractAtherosclerotic disease progression in coronary arteries is influenced by wall shear stress. To compute patient-specific wall shear stress, computational fluid dynamics (CFD) is required. In this study we propose a method for computing the pressure-drop in regions proximal and distal to

  7. 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

  8. Atherosclerotic risk and social jetlag in rotating shift-workers : first evidence from a pilot study

    NARCIS (Netherlands)

    Kantermann, Thomas; Duboutay, Françoise; Haubruge, Damien; Kerkhofs, Myriam; Schmidt-Trucksäss, Arno; Skene, Debra J

    2013-01-01

    OBJECTIVE: The aim of this study was to identify atherosclerotic risk using pulse wave velocity (PWV) in steel workers employed in different shift-work rotations, and to elucidate its relationship to social jetlag and shift schedule details. PARTICIPANTS: Male workers in a steel factory (n=77, 32 fa

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...

  10. 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.

  11. Post-interventional atherosclerotic vascular remodeling : preclinical investigation into immune-modulatory therapies

    NARCIS (Netherlands)

    Ewing, Mark McConnell

    2013-01-01

    Cardiovascular diseases remain the major cause of death throughout the world and can be primarily attributed to atherosclerotic vascular disease leading to stroke and coronary heart disease (CHD). Improved primary prevention and the introduction and subsequent optimization of percutaneous coronary i

  12. Treatment of periodontitis improves the atherosclerotic profile: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Teeuw, W.J.; Slot, D.E.; Susanto, H.; Gerdes, V.E.A.; Abbas, F.; D'Aiuto, F.; Kastelein, J.J.P.; Loos, B.G.

    2014-01-01

    Aim Systematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. Material and Methods Literature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials, incl

  13. Repair of an Atherosclerotic Coronary Artery Aneurysm by Implantation of a Coronary Covered Stent

    Directory of Open Access Journals (Sweden)

    Antenor Portela

    2002-05-01

    Full Text Available An atherosclerotic aneurysm of the right coronary artery complicated by a recent myocardial infarction was successfully treated with coronary artery stenting, using a device consisting of 2 stents with a layer of expandable polytetrafluorethylene (PTFE placed between them. A follow-up angiograph 5 months after the procedure showed sustained initial results.

  14. 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...

  15. 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.

  16. 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

  17. Imaging the Intracranial Atherosclerotic Vessel Wall Using 7T MRI : Initial Comparison with Histopathology

    NARCIS (Netherlands)

    van der Kolk, A. G.; Zwanenburg, J. J. M.; Denswil, N. P.; Vink, A.; Spliet, W. G. M.; Daemen, M. J. A. P.; Visser, F.; Klomp, D. W. J.; Luijten, P. R.; Hendrikse, J.

    2015-01-01

    In this preliminary study, 7T imaging was capable of identifying not only intracranial wall thickening but different plaque components such as foamy macrophages and collagen. Signal heterogeneity was typical of advanced atherosclerotic disease. BACKGROUND AND PURPOSE: Several studies have attempted

  18. 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.

  19. VCAM-1-targeting gold nanoshell probe for photoacoustic imaging of atherosclerotic plaque in mice.

    Science.gov (United States)

    Rouleau, Leonie; Berti, Romain; Ng, Vanessa W K; Matteau-Pelletier, Carl; Lam, Tina; Saboural, Pierre; Kakkar, Ashok K; Lesage, Frédéric; Rhéaume, Eric; Tardif, Jean-Claude

    2013-01-01

    The development of molecular probes and novel imaging modalities, allowing better resolution and specificity, is associated with an increased potential for molecular imaging of atherosclerotic plaques especially in basic and pre-clinical research applications. In that context, a photoacoustic molecular probe based on gold nanoshells targeting VCAM-1 in mice (immunonanoshells) was designed. The molecular probe was validated in vitro and in vivo, showing no noticeable acute toxic effects. We performed the conjugation of gold nanoshells displaying near-infrared absorption properties with VCAM-1 antibody molecules and PEG to increase their biocompatibility. The resulting immunonanoshells obtained under different conditions of conjugation were then assessed for specificity and sensitivity. Photoacoustic tomography was performed to determine the ability to distinguish gold nanoshells from blood both in phantoms and in vivo. Ex vivo optical projection tomography of hearts and aortas from atherosclerotic and control mice confirmed the selective accumulation of the immunonanoshells in atherosclerotic-prone regions in mice, thus validating the utility of the probe in vivo in small animals for pre-clinical research. These immunonanoshells represent an adequate mean to target atherosclerotic plaques in small animals, leading to new tools to follow the effect of therapies on the progression or regression of the disease.

  20. 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...

  1. Treatment of periodontitis improves the atherosclerotic profile : a systematic review and meta-analysis

    NARCIS (Netherlands)

    Teeuw, Wijnand J.; Slot, Dagmar E.; Susanto, Hendri; Gerdes, Victor E. A.; Abbas, Frank; D'Aiuto, Francesco; Kastelein, John J. P.; Loos, Bruno G.

    2014-01-01

    AimSystematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. Material and MethodsLiterature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials, includ

  2. 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

  3. Relapses in inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Blas J. Larrauri

    2016-12-01

    Full Text Available Most studies about treatment of inflammatory myopathies consist of cross-sectional analyses that do not assess long-term efficacy. In the present study we describe the follow-up of seven patients with inflammatory myopathies, 5 polymyositis and 2 dermatomyositis. We describe their clinical features, follow-up, muscle enzyme levels, and treatment responses. We define the latter as treatment cycles, every one of which end when steroid doses need to be increased or a new immunosuppressive drug has to be added because of clinical worsening or sustained increases in muscle enzyme levels. Treatment can cause remission, partially control, or fail in achieving myositis improvement when it normalizes, stabilizes, or does not affect muscle enzymes or clinical features, respectively. We analyzed 20 cycles, in which remission was achieved in 14 cases, partial control in 5 instances, and treatment failure in one case. Remission occurred after an average of 139 ± 98 days, whereas partial control took place in 160 ± 100 days. Except in one case, all treatment cycles controlled or remitted the symptoms. However, in all patients the illness recurred with time.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Wen-yi Wang

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

  6. 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

  7. Chronic inflammatory demyelinating polyneuropathy

    Science.gov (United States)

    Polyneuropathy - chronic inflammatory; CIDP; Chronic inflammatory polyneuropathy; Guillain-Barré - CIDP ... Health care providers also consider CIDP as the chronic form of Guillain-Barré syndrome. The specific triggers ...

  8. The Immune Response Is Involved in Atherosclerotic Plaque Calcification: Could the RANKL/RANK/OPG System Be a Marker of Plaque Instability?

    Directory of Open Access Journals (Sweden)

    Fabrizio Montecucco

    2007-01-01

    Full Text Available Atherogenesis is characterized by an intense inflammatory process, involving immune and vascular cells. These cells play a crucial role in all phases of atherosclerotic plaque formation and complication through cytokine, protease, and prothrombotic factor secretion. The accumulation of inflammatory cells and thus high amounts of soluble mediators are responsible for the evolution of some plaques to instable phenotype which may lead to rupture. One condition strongly associated with plaque rupture is calcification, a physiopathological process orchestrated by several soluble factors, including the receptor activator of nuclear factor NFκB ligand (RANKL/receptor activator of nuclear factor NFκB (RANK/osteoprotegerin (OPG system. Although some studies showed some interesting correlations with acute ischemic events, at present, more evidences are needed to evaluate the predictive and diagnostic value of serum sRANKL and OPG levels for clinical use. The major limitation is probably the poor specificity of these factors for cardiovascular disease. The identification of tissue-specific isoforms could increase the importance of sRANKL and OPG in predicting calcified plaque rupture and the dramatic ischemic consequences in the brain and the heart.

  9. The immune response is involved in atherosclerotic plaque calcification: could the RANKL/RANK/OPG system be a marker of plaque instability?

    Science.gov (United States)

    Montecucco, Fabrizio; Steffens, Sabine; Mach, François

    2007-01-01

    Atherogenesis is characterized by an intense inflammatory process, involving immune and vascular cells. These cells play a crucial role in all phases of atherosclerotic plaque formation and complication through cytokine, protease, and prothrombotic factor secretion. The accumulation of inflammatory cells and thus high amounts of soluble mediators are responsible for the evolution of some plaques to instable phenotype which may lead to rupture. One condition strongly associated with plaque rupture is calcification, a physiopathological process orchestrated by several soluble factors, including the receptor activator of nuclear factor (NF)kappaB ligand (RANKL)/receptor activator of nuclear factor (NF)kappaB (RANK)/osteoprotegerin (OPG) system. Although some studies showed some interesting correlations with acute ischemic events, at present, more evidences are needed to evaluate the predictive and diagnostic value of serum sRANKL and OPG levels for clinical use. The major limitation is probably the poor specificity of these factors for cardiovascular disease. The identification of tissue-specific isoforms could increase the importance of sRANKL and OPG in predicting calcified plaque rupture and the dramatic ischemic consequences in the brain and the heart.

  10. 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.

  11. Mitochondrial dysfunction leads to deconjugation of quercetin glucuronides in inflammatory macrophages.

    Directory of Open Access Journals (Sweden)

    Akari Ishisaka

    Full Text Available Dietary flavonoids, such as quercetin, have long been recognized to protect blood vessels from atherogenic inflammation by yet unknown mechanisms. We have previously discovered the specific localization of quercetin-3-O-glucuronide (Q3GA, a phase II metabolite of quercetin, in macrophage cells in the human atherosclerotic lesions, but the biological significance is poorly understood. We have now demonstrated the molecular basis of the interaction between quercetin glucuronides and macrophages, leading to deconjugation of the glucuronides into the active aglycone. In vitro experiments showed that Q3GA was bound to the cell surface proteins of macrophages through anion binding and was readily deconjugated into the aglycone. It is of interest that the macrophage-mediated deconjugation of Q3GA was significantly enhanced upon inflammatory activation by lipopolysaccharide (LPS. Zymography and immunoblotting analysis revealed that β-glucuronidase is the major enzyme responsible for the deglucuronidation, whereas the secretion rate was not affected after LPS treatment. We found that extracellular acidification, which is required for the activity of β-glucuronidase, was significantly induced upon LPS treatment and was due to the increased lactate secretion associated with mitochondrial dysfunction. In addition, the β-glucuronidase secretion, which is triggered by intracellular calcium ions, was also induced by mitochondria dysfunction characterized using antimycin-A (a mitochondrial inhibitor and siRNA-knockdown of Atg7 (an essential gene for autophagy. The deconjugated aglycone, quercetin, acts as an anti-inflammatory agent in the stimulated macrophages by inhibiting the c-Jun N-terminal kinase activation, whereas Q3GA acts only in the presence of extracellular β-glucuronidase activity. Finally, we demonstrated the deconjugation of quercetin glucuronides including the sulfoglucuronides in vivo in the spleen of mice challenged with LPS. These results

  12. Heme oxygenase-1 against vascular insufficiency: roles of atherosclerotic disorders.

    Science.gov (United States)

    Ishikawa, Kazunobu

    2003-01-01

    Heme oxygenase (HO), an enzyme essential for heme degradation, shows anti-oxidative and anti-inflammatory properties via the production of bile pigments, carbon monoxide (CO) and ferritin induction under various pathophysiological conditions. A number of recent studies have shown biological effects of HO reaction in cardiovascular disorders. An inducible form of HO, HO-1, is induced by a variety of stresses such as oxidized lipoproteins, cytokines, hemodynamic changes, angiotensin II and nitric oxide (NO) in vascular wall. HO-1 induction seems to function as an adaptive response against these injurious stimuli. HO-1 induction in artery wall scavenges reactive oxygen species, which leads to the attenuation of monocyte adhesion and chemotaxis. HO-1 induction also reduces lipid peroxidation in plasma and artery wall. These properties of HO-1 suggest anti-atherogenic roles of this enzyme. In this review, roles of endothelial HO-1 expression and bilirubin in atherogenesis are also discussed. HO-1 also seems to play a significant role in restenosis after angioplasty, which is a major clinical problem associated with atherosclerosis. Recent progress in human HO-1 genetics supports these experimental results. This review aims to reaffirm current problems in the biological aspects of HO and suggest future research direction and clinical application.

  13. 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

  14. 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...

  15. Cholesterol and prevention of atherosclerotic events: limits of a new frontier

    Science.gov (United States)

    de Macedo, Luís Eduardo Teixeira; Faerstein, E

    2016-01-01

    ABSTRACT Control of atherosclerotic cardiovascular disease – a highly prevalent condition and one of the main causes of mortality in Brazil and worldwide – is a recurrent subject of great interest for public health. Recently, three new guidelines on dyslipidemia and atherosclerosis prevention have been published. The close release of these important publications is a good opportunity for comparison: the Brazilian model has greater sensitivity, the English model does not work with risk stratification, and the American model may be overestimating the risk. This will allow reflection on current progress and identification of controversial aspects which still require further research and debate. It is also an opportunity to discuss issues related to early diagnosis and its efficiency as a preventive strategy for atherosclerotic disease: the transformation of risk into disease, the gradual reduction of cut-off points, the limitations of the screening strategy, and the problem of overdiagnosis. PMID:28099551

  16. 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...

  17. Evaluation of 99mTc Labeled Diadenosine Tetraphosphate as an Atherosclerotic Plaque Imaging Agent in Experimental Models

    Institute of Scientific and Technical Information of China (English)

    CAO Wei; ZHANG Yongxue; AN Rui

    2006-01-01

    The potential of 99m Tc labeled P1, P4-di (adenosine-5')-tetraphosphate (Ap4A) for imaging experimental atherosclerotic plaques was evaluated in New Zealand white (NZW) rabbits. To label the 99mTc to Ap4A, stannous tartrate solution was used. 99mTc-Ap4A was purified on a Sephadex G-25 column. The radiochemistry purities of 99mTc-Ap4A were 85% to 91%. Biodistribution study revealed 99mTc-Ap4A cleared from blood rapidly. Thirty min after 99mTc-Ap4A administrated on NZW atherosclerotic rabbits, lesion to blood (target/blood, T/B) ratio was 3.17±1.27, and lesions to normal (target/non-target, T/NT) ratio was 5.23±1.87. Shadows of atherosclerotic plaques were clearly visible on radioautographic film. Aortas with atherosclerotic plaques also could be seen on ex vivo gamma camera images. Atherosclerotic abdominal aortas were clearly visible on in vivo images 15 min to 3 h after 99mTc-Ap4A administration. 99mTc-labeled Ap4A can be used for rapid noninvasive detection of experimental atherosclerotic plaque.

  18. 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.

  19. 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.

  20. Effect of renal revascularization on the development of renal dysfunction in atherosclerotic ischemic nephropathy

    OpenAIRE

    Rodrigo Hagemann; Vanessa dos Santos Silva; Roberto Jorge da Silva Franco; Pasqual Barretti; Luis Cuadrado Martin

    2014-01-01

    Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension is atherosclerotic renal disease (ARD). The development of CKD in patients with ARD appears to be due not only to the involvement of the main renal arteries, but also of the renal microcirculation, which may explain the fact that the success of the procedure does not guarantee an improvement in the progression of CKD...

  1. Association of Thrombomodulin Gene Polymorphisms with Susceptibility to Atherosclerotic Diseases: A Meta-Analysis.

    Science.gov (United States)

    Xu, Jie; Jin, Jun; Tan, Sheng

    2016-05-01

    Previous studies have proved that the dysfunction of thrombomodulin (TM) plays an important role in the pathogenesis of atherosclerotic diseases. In order to reveal their inherent relationship, we conducted a meta-analysis to uncover the association between two polymorphisms -33G/A and Ala455Val (c.1418C>T) in the TM gene and atherosclerotic diseases. We carried out a systematic search in PubMed, Science Direct, BIOSIS Previews, SpringerLink, the Cochrane library, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Database, the Wei Pu database, and the Wanfang Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed to show the association. We included 22 eligible studies which involved 5472 patients and 7786 controls. There were statistically significant associations between -33G/A polymorphisms in TM and the MI group under the Allele and Recessive models in Asians (G vs. A: OR = 0.67, 95%CI = 0.56-0.78, P < 0.00001; GG vs. GA+AA: OR = 0.66, 95%CI = 0.56-0.78, P < 0.00001). However, these findings of the overall and subgroups showed that Ala455Val polymorphisms did not have any relationship with atherosclerotic diseases. After Bonferroni correction, the above associations remained statistically significant. This meta-analysis provides robust evidence of association between the -33G/A polymorphism in the TM gene and the risk of myocardial infarction in Asians. The A allele may increase the incidence of MI in Asians. However, the Ala455Val variant was not associated with atherosclerotic risk. Further studies with adequate sample size are needed to verify our findings.

  2. Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques.

    Science.gov (United States)

    Yatera, Kazuhiro; Hsieh, Joanne; Hogg, James C; Tranfield, Erin; Suzuki, Hisashi; Shih, Chih-Horng; Behzad, Ali R; Vincent, Renaud; van Eeden, Stephan F

    2008-02-01

    Epidemiologic studies have shown an association between exposure to ambient particulate air pollution <10 microm in diameter (PM(10)) and increased cardiovascular morbidity and mortality. We previously showed that PM(10) exposure causes progression of atherosclerosis in coronary arteries. We postulate that the recruitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM(10)-induced acceleration of atherosclerosis. The study objective was to quantify the recruitment of circulating monocytes into vessel walls and the progression of atherosclerotic plaques induced by exposure to PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo-2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM(10) caused progression of atherosclerotic lesions in thoracic and abdominal aorta. It also decreased circulating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platelet endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the number of BrdU-labeled monocytes adherent to endothelium over plaques and increased the migration of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conclude that exposure to ambient air pollution particles promotes the recruitment of circulating monocytes into atherosclerotic plaques and speculate that this is a critically important step in the PM(10)-induced progression of atherosclerosis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-06-15

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

  4. Stenting for Atherosclerotic Stenosis of the Intracranial or Skull Base Cerebral Arteries: Effectiveness and Problems

    OpenAIRE

    Harakuni, T.; Hyodo, A.; Shingaki, T.; Kugai, M.; Kinjyo, T.; Tsuchida, H.; Sugimoto, K.; Yoshii, Y.; Matsumaru, Y.

    2004-01-01

    Since May 1992, we have performed percutaneous transluminal angioplasty (PTA) or stenting 70 times for 65 lesions in 62 patients with atherosclerotic stenosis of the intracranial or skull base cerebral arteries. Stenting was carried out nine times for nine lesions in nine cases. Stenting was performed on patients with an average age of 62. The patients were eight men and one woman. The stenotic lesions involved the internal carotid artery (petrous portion) in four cases, the internal carotid ...

  5. 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

  6. Laser-induced fluorescence: quantitative analysis of atherosclerotic plaque chemical content in human aorta

    Science.gov (United States)

    Dai, Erbin; Wishart, David; Khoury, Samir; Kay, Cyril M.; Jugdutt, Bodh I.; Tulip, John; Lucas, Alexandra

    1996-05-01

    We have been studying laser-induced fluorescence as a technique for identification of selected changes in the chemical composition of atherosclerotic plaque. Formulae for quantification of chemical changes have been developed based upon analysis of fluorescence emission spectra using multiple regression analysis and the principal of least squares. The intima of human aortic necropsy specimens was injected with chemical compounds present in atherosclerotic plaque. Spectra recorded after injection of selected chemical components found in plaque (collagen I, III, IV, elastin and cholesterol) at varying concentrations (0.01 - 1.0 mg) were compared with saline injection. A single fiber system was used for both fluorescence excitation (XeCl excimer laser, 308 nm, 1.5 - 2.0 mJ/ pulse, 5 Hz) and fluorescence emission detection. Average spectra for each chemical have been developed and the wavelengths of peak emission intensity identified. Curve fitting analysis as well as multiple regression analysis were used to develop formulae for assessment of chemical content. Distinctive identifying average curves were established for each chemical. Excellent correlations were identified for collagen I, III, and IV, elastin, and cholesterol (R2 equals 0.92 6- 0.997). Conclusions: (1) Fluorescence spectra of human aortas were significantly altered by collagen I, collagen III, elastin and cholesterol. (2) Fluorescence spectroscopic analysis may allow quantitative assessment of atherosclerotic plaque chemical content in situ.

  7. 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.

  8. Overexpression of ABCG1 protein attenuates arteriosclerosis and endothelial dysfunction in atherosclerotic rabbits

    Directory of Open Access Journals (Sweden)

    Martin Ungerer

    2012-06-01

    Full Text Available The ABCG1 protein is centrally involved in reverse cholesterol transport from the vessel wall. Investigation of the effects of ABCG1 overexpression or knockdown in vivo has produced controversial results and strongly depended on the gene intervention model in which it was studied. Therefore, we investigated the effect of local overexpression of human ABCG1 in a novel model of vessel wall-directed adenoviral gene transfer in atherosclerotic rabbits. We conducted local, vascular-specific gene transfer by adenoviral delivery of human ABCG1 (Ad-ABCG1-GFP in cholesterol-fed atherosclerotic rabbits in vivo. Endothelial overexpression of ABCG1 markedly reduced atheroprogression (plaque size and almost blunted vascular inflammation, as shown by markedly reduced macrophage and smooth muscle cell invasion into the vascular wall. Also endothelial function, as determined by vascular ultrasound in vivo, was improved in rabbits after gene transfer with Ad-ABCG1-GFP. Therefore, both earlier and later stages of atherosclerosis were improved in this model of somatic gene transfer into the vessel wall. In contrast to results in transgenic mice, overexpression of ABCG1 by somatic gene transfer to the atherosclerotic vessel wall results in a significant improvement of plaque morphology and composition, and of vascular function in vivo.

  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. 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.

  11. Ex vivo detection of macrophages in atherosclerotic plaques using intravascular ultrasonic-photoacoustic imaging

    Science.gov (United States)

    Quang Bui, Nhat; Hlaing, Kyu Kyu; Lee, Yong Wook; Kang, Hyun Wook; Oh, Junghwan

    2017-01-01

    Macrophages are excellent imaging targets for detecting atherosclerotic plaques as they are involved in all the developmental stages of atherosclerosis. However, no imaging technique is currently capable of visualizing macrophages inside blood vessel walls. The current study develops an intravascular ultrasonic-photoacoustic (IVUP) imaging system combined with indocyanine green (ICG) as a contrast agent to provide morphological and compositional information about the targeted samples. Both tissue-mimicking vessel phantoms and atherosclerotic plaque-mimicking porcine arterial tissues are used to demonstrate the feasibility of mapping macrophages labeled with ICG by endoscopically applying the proposed hybrid technique. A delay pulse triggering technique is able to sequentially acquire photoacoustic (PA) and ultrasound (US) signals from a single scan without using any external devices. The acquired PA and US signals are used to reconstruct 2D cross-sectional and 3D volumetric images of the entire tissue with the ICG-loaded macrophages injected. Due to high imaging contrast and sensitivity, the IVUP imaging vividly reveals structural information and detects the spatial distribution of the ICG-labeled macrophages inside the samples. ICG-assisted IVUP imaging can be a feasible imaging modality for the endoscopic detection of atherosclerotic plaques.

  12. 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.

  13. 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

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

    Science.gov (United States)

    Dmitrieva, Natalia I; Burg, Maurice B

    2015-01-01

    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 risk factor for

  15. Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms.

    Science.gov (United States)

    Alexander, Matthew R; Murgai, Meera; Moehle, Christopher W; Owens, Gary K

    2012-04-02

    Smooth muscle cell (SMC) phenotypic modulation in atherosclerosis and in response to PDGF in vitro involves repression of differentiation marker genes and increases in SMC proliferation, migration, and matrix synthesis. However, SMCs within atherosclerotic plaques can also express a number of proinflammatory genes, and in cultured SMCs the inflammatory cytokine IL-1β represses SMC marker gene expression and induces inflammatory gene expression. Studies herein tested the hypothesis that IL-1β modulates SMC phenotype to a distinct inflammatory state relative to PDGF-DD. Genome-wide gene expression analysis of IL-1β- or PDGF-DD-treated SMCs revealed that although both stimuli repressed SMC differentiation marker gene expression, IL-1β distinctly induced expression of proinflammatory genes, while PDGF-DD primarily induced genes involved in cell proliferation. Promoters of inflammatory genes distinctly induced by IL-1β exhibited over-representation of NF-κB binding sites, and NF-κB inhibition in SMCs reduced IL-1β-induced upregulation of proinflammatory genes as well as repression of SMC differentiation marker genes. Interestingly, PDGF-DD-induced SMC marker gene repression was not NF-κB dependent. Finally, immunofluorescent staining of mouse atherosclerotic lesions revealed the presence of cells positive for the marker of an IL-1β-stimulated inflammatory SMC, chemokine (C-C motif) ligand 20 (CCL20), but not the PDGF-DD-induced gene, regulator of G protein signaling 17 (RGS17). Results demonstrate that IL-1β- but not PDGF-DD-induced phenotypic modulation of SMC is characterized by NF-κB-dependent activation of proinflammatory genes, suggesting the existence of a distinct inflammatory SMC phenotype. In addition, studies provide evidence for the possible utility of CCL20 and RGS17 as markers of inflammatory and proliferative state SMCs within atherosclerotic plaques in vivo.

  16. Comparison of anti-atherosclerotic effects of two different extracts from leaves ofMallotus furetianus

    Institute of Scientific and Technical Information of China (English)

    Liu Yueli; Wang Liqun; Wu Haitao; Lin Lianbo; Yi Xinan

    2011-01-01

    Objective:To compare the anti-atherosclerotic effects of two different extracts from the leaves ofMallotus furetianus by using rat model of atherosclerosis.Methods: The air-dried powdered Mallotus furetianus leaves were extracted with ethanol and then evaporated. The ethanol extract was experienced DiaionHP-20 CC with a gradient ofMeOH andH2O (50÷50,100÷0, v/v) and two fractions,Mallotus furetianusA (MfA) andMallotus furetianusB (MfB) were obtained. Rats were divided into control, atherosclerosis and vitaminE,MfA andMfB treated groups. Atherosclerotic model was established by administering a loading dose of vitaminD3 and feeding standard diet enriched with2% cholesterol,0.5% porcine cholate,0.2% methimazole, 5% sugar,10% pork fat. VitaminE (0.20 g/kg),MfA (0.053 g/kg),MfB (0.057 g/kg) (with the potential) were administered to interfere with the development of atherosclerosis. After9 weeks, rats were sacrificed and the blood lipid as well as composition of bile was examined. In addition, the thoracic aorta was harvested to evaluate histological changes and the intima-media thickness ratio.Results:Atherosclerosis model was successfully established, administration of vitaminE,MfA andMf Bincreased excretion of total bilirubin in bile, decreased triglyeride (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) level, enhanced ratio of high density lipoprotein-cholesterol andLDL-C in blood, improved histological changes and diminished intima-media thickness ratio of thoracic aorta in atherosclerotic rats. As for the difference in anti-atherosclerotic effects betweenMfA andMfB,MfA may be more powerful in decliningTG level andMfB may be more effective in decreasingTC level.Conclusions:The two different extracts, MfA andMfB can prevent the development of atherosclerosis, In detail,MfA is more effective in regulatingTG level andMfB is more powerful in modulatingTC level in atherosclerotic rats.

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

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    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.

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

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    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.

  19. 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

  20. Biomechanics and inflammation in atherosclerotic plaque erosion and plaque rupture: implications for cardiovascular events in women.

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    Ian C Campbell

    Full Text Available Although plaque erosion causes approximately 40% of all coronary thrombi and disproportionally affects women more than men, its mechanism is not well understood. The role of tissue mechanics in plaque rupture and regulation of mechanosensitive inflammatory proteins is well established, but their role in plaque erosion is unknown. Given obvious differences in morphology between plaque erosion and rupture, we hypothesized that inflammation in general as well as the association between local mechanical strain and inflammation known to exist in plaque rupture may not occur in plaque erosion. Therefore, our objective was to determine if similar mechanisms underlie plaque rupture and plaque erosion.We studied a total of 74 human coronary plaque specimens obtained at autopsy. Using lesion-specific computer modeling of solid mechanics, we calculated the stress and strain distribution for each plaque and determined if there were any relationships with markers of inflammation. Consistent with previous studies, inflammatory markers were positively associated with increasing strain in specimens with rupture and thin-cap fibroatheromas. Conversely, overall staining for inflammatory markers and apoptosis were significantly lower in erosion, and there was no relationship with mechanical strain. Samples with plaque erosion most closely resembled those with the stable phenotype of thick-cap fibroatheromas.In contrast to classic plaque rupture, plaque erosion was not associated with markers of inflammation and mechanical strain. These data suggest that plaque erosion is a distinct pathophysiological process with a different etiology and therefore raises the possibility that a different therapeutic approach may be required to prevent plaque erosion.

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

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    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.

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

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    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

  3. Inflammatory myofibroblastic tumour of maxilla

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    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.

  4. Biomarkers of Chronic Inflammatory State in Uremia and Cardiovascular Disease

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    Vincenzo Panichi

    2012-01-01

    Full Text Available Cardiovascular disease is the leading cause of death in the general population; traditional risk factors seem inadequate to explain completely the remarkable prevalence of cardiovascular mortality and morbidity observed in the uremic population. A role for chronic inflammation has been well established in the development of atherosclerotic disease, and, on the basis of these observations, atherosclerosis might be considered an inflammatory disease. Inflammation has been implicated in the etiology of coronary artery disease in the general population, and traditional inflammatory biomarkers such as C-reactive protein (CRP and interleukin-6 (IL-6 have been shown to predict cardiovascular events in both symptomatic and asymptomatic individuals as well as those in the uremic population. Later on, new nontraditional markers were related to the risk of cardiovascular morbidity and mortality in general and in uremic population. As a consequence of the expanding research base and availability of assays, the number of inflammatory marker tests ordered by clinicians for cardiovascular disease (CVD risk prediction has grown rapidly and several commercial assays have become available. So, up to now we can consider that several new nontraditional markers as CD40-CD40 ligand system and pentraxin-3 seem to be significant features of cardiovascular disease in general and in ESRD population.

  5. 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.

  6. 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.

  7. [Inflammatory dendritic cells].

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    Segura, Elodie; Amigorena, Sebastian

    2014-01-01

    Dendritic cells are a rare and heterogeneous population of professional antigen-presenting cells. Several murine dendritic cell subpopulations have been identified that differ in their phenotype and functional properties. In the steady state, committed dendritic cell precursors differentiate into lymphoid organ-resident dendritic cells and migratory tissue dendritic cells. During inflammation appears an additional dendritic cell subpopulation that has been termed « inflammatory dendritic cells ». Inflammatory dendritic cells differentiate in situ from monocytes recruited to the site of inflammation. Here, we discuss how mouse inflammatory dendritic cells differ from macrophages and from other dendritic cell populations. Finally, we review recent work on human inflammatory dendritic cells.

  8. Chronic Inflammatory Polyneuropathy

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    J Gordon Millichap

    2007-02-01

    Full Text Available Thirteen children with chronic inflammatory demyelinating polyneuropathy monitored between 1975 and 2005 are reported from Centre hospitalier universitaire Sainte-Justine, Montreal, Canada.

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

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    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.

  10. [Inflammatory neuropathies and multineuritis].

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    Kuntzer, Thierry; Chofflon, Michel

    2009-12-02

    Inflammatory neuropathies include those neuropathies in which the diagnosis, outcome and type of treatment are badly known, the reason of this review. They are expressed as diffuse (such as CIDP and ganglionopathies), multifocal (vasculitic neuropathy) or focal (MMN; plexopathies; immune reconstitution inflammatory syndrome). These forms of neuropathies are important to be known because the beneficial therapeutic possibilities of immunosuppression.

  11. [Pathogenesis of the idiopathic inflammatory myopathies].

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    Riebeling-Navarro, Carlos; Nava, Arnulfo

    2009-11-01

    The inflammatory myopathies, commonly described as idiopathic, are a group of acquired diseases characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical and immuno-pathological features, three major diseases can be identified: dermatomiositis (DM), polymyositis (PM) and inclusion body myositis (IBM). Immunopathogenesis mechanisms are crucial for discriminating between the three different subsets of inflammatory myopathies. 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. This article summarizes the main immunopathological markers. The impact of this new knowledge must be defined in relation to potential therapeutic targets for idiopathic inflammatory myopathies.

  12. 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.

  13. Atherosclerotic vessel damage in systemic lupus erythematosus and antiphospholipid syndrome in men

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    A. I. Iljina

    2005-01-01

    Full Text Available Objective. To study prevalence of clinical and subclinical atherosclerosis signs in men with systemic lupus erythematosus (SLE and antiphospholipid syndrome, to assess relationship between atherosclerotic vessel damage, risk factors, CRP and anti-cardiolipin antibodies (АСА Material and methods. 62 pts were included. Mean age was 35,7+11,6 years, mean disease duration - 129,3± 102 months. Traditional and related to the disease risk factors were analyzed. To reveal atherosclerotic vessel damage carotid sonographic examination was performed. Serum CRP concentration was evaluated by high sensitivity nephelometric immunoassay. IgG and IgM АСА were assessed by solid-phase immuno-enzyme assay. Results. Sonographic signs of carotid damage was revealed in 58% of pts, clinical signs of atherosclerosis - in 42%. Pts were divided into two groups according to intima-media complex thickness (IMCT. Group I included 36 pts with atherosclerotic vessel damage signs (IMCT?0,9 mm. Group 2-26 pts with IMCT<0,9 mm. Mean age at the examination, age of disease onset, disease duration, smoking frequency damage index in group I pts were higher than in group 2 pts. Mean CRP concentration in atherosclerosis group was significantly higher than in group 2 (p=0,007. 19 pts had APS signs. 43 pts did not. CRP level significantly correlated with IMCT in SLE pts with and without APS (p<0,05. Pts with atherosclerosis had higher IgG АСА level though the differences were not statistically significant. Conclusion. Men with SLE with or without APS have high risk of atherosclerosis development. CRP elevation is associated with IMCT increase.

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

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    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.

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

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    Li Tao [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhao Xihai [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Liu Xin [Paul C. Lauterbur Biomedical Imaging Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen 518067 (China); Gao Jianhua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Zhao Shaohong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Li Xin; Zhou Weihua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Cai Zulong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhang Weiguo [Cardiovascular and Neurological Consulting Institute, 6771 San Fernando, Irving, TX 75039 (United States); Yang Li, E-mail: Yangli301@yahoo.com [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China)

    2011-10-15

    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.

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

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    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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. [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.

  2. 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.

  3. Effect of AVE 0991 angiotensin-(1-7) receptor agonist treatment on elemental and biomolecular content and distribution in atherosclerotic plaques of apoE-knockout mice

    Science.gov (United States)

    Kowalska, J.; Gajda, M.; Jawień, J.; Kwiatek, W. M.; Appel, K.; Dumas, P.

    2013-12-01

    Gene-targeted apolipoprotein E-knockout (apoE-KO) mice display early and highly progressive vascular lesions containing lipid deposits and they became a reliable animal model to study atherosclerosis. The aim of the present study was to investigate the effect of AVE 0991 angiotensin-(1-7) receptor agonist on the distribution of selected pro- and anti- inflammatory elements as well as biomolecules in atherosclerotic plaques of apoE-knockout mice. Synchrotron radiation-based X-ray fluorescence (micro-XRF) and Fourier Transform Infrared (micro-FTIR) microspectroscopies were applied. Two-month-old apoE-KO mice were fed for following four months diet supplemented with AVE 0991 (0.58 μmol/kg b.w. per day). Histological sections of ascending aortas were analyzed spectroscopically. The distribution of P, Ca, Fe and Zn were found to correspond with histological structure of the lesion. Significantly lower contents of P, Ca, Zn and significantly higher content of Fe were observed in animals treated with AVE 0991. Biomolecular analysis showed lower lipids saturation level and lower lipid to protein ratio in AVE 0991 treated group. Protein secondary structure was studied according to the composition of amide I band (1660 cm-1) and it demonstrated higher proportion of β-sheet structure as compared to α-helix in both studied groups.

  4. 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.

  5. 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.

  6. 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.

  7. Hemodynamic outcome of successful bypass surgery in patients with atherosclerotic cerebrovascular disease: a study with acetazolamide and {sup 99m}Tc-ECD SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Eo, Jae Seon; Oh, Chang Wan; Kim, Yu Kyeong; Park, Eun Kyung; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2006-12-15

    The aim of the study was to evaluate the hemodynamic changes after successful bypass surgery in patients with atherosclerotic stenosis in ICA using {sup 99m}Tc-ECD SPECT. Fourteen patients (M:F = 8:6, mean age; 60 {+-} 9 years) who underwent STA-MCA anastomosis for unilateral atherosclerotic cerebrovascular disease were enrolled. {sup 99m}Tc-ECD basal/acetazolamide perfusion SPECT studies were performed before, 10 days and 6 months after bypass surgery. Perfusion reserve was defined as the % changes after acetazolamide over rest image. Regional cerebral blood flow and perfusion reserve were compared preoperative, early-postoperative and late-postoperative scans. The mean resting perfusion and decrease in perfusion reserve in affected ICA territory on preoperative scan was 52.4 {+-} 3.5 and -7.9 {+-} 4.7%, respectively. The resting perfusion was significantly improved after surgery on early-postoperative scan (mean 53.7 {+-} 2.7) and late-postoperative scan (mean 53.3 {+-} 2.5) compared with preoperative images ({rho} < 0.05, respectively). Resting perfusion did not showed further improvement on late-postoperative scan compared with early-postoperative scan. The perfusion reserve was -3.7 {+-} 2.6% on early-postoperative scan, and -1.6 {+-} 2.3% on late-postoperative scan, which was significantly improved after surgery. Additionally, further improvement of perfusion reserved a observed on late-postoperative scan ({rho} < 0.05). While, in the unaffected ICA territory, on significant changes in the resting perfusion and perfusion reserve was observed. The improvement of resting perfusion and perfusion reserve in early-postoperative scan reflects the immediate restoration of the cerebral blood flow by bypass surgery. In contrasts, further improvement of perfusion reserve showing on late-postoperative scan may indicate a good collateral development after surgery, which may indicate good surgical outcome after surgery.

  8. Long-Term Clinical Outcomes According to Previous Manifestations of Atherosclerotic Disease (from the FAST-MI 2010 Registry).

    Science.gov (United States)

    Puymirat, Etienne; Aissaoui, Nadia; Lemesle, Gilles; Cottin, Yves; Coste, Pierre; Schiele, François; Ferrières, Jean; Simon, Tabassome; Danchin, Nicolas

    2017-03-01

    The prognosis of patients with acute myocardial infarction (AMI) has notably improved in the past 20 years. Using the French Registry of ST-Elevation and Non-ST-elevation Myocardial Infarction (FAST-MI) 2010 registry, we investigated whether previous manifestations of atherosclerotic disease (i.e., previous MI, or a history of any form of atherosclerotic disease) are at truly increased risk compared with those in whom AMI is the first manifestation of the disease. FAST-MI 2010 is a nationwide French registry including 3,079 patients with AMI, among whom 1,062 patients had a history of cardiovascular atherosclerotic disease and 498 patients had a history of MI. Overall, patients with a history of atherosclerotic disease (or MI) were older compared with patients without known cardiovascular disease (71 ± 13 vs 63 ± 14 years) and had higher cardiovascular risk profiles and co-morbidities. Using fully adjusted Cox multivariate analysis, previous manifestations of atherosclerotic disease were associated with higher 3-year mortality (hazard ratio 1.80, 95% confidence interval 1.40 to 2.31; p <0.001) as history of previous MI alone (hazard ratio 1.32, 95% confidence interval 1.00 to 1.73; p = 0.048). Similar results were found in patients discharged alive. In conclusion, previous cardiovascular atherosclerotic disease represents 1/3 of patients with AMI and are strongly associated with worse long-term clinical outcomes. Intensive follow-up and therapy should be encouraged in this high-risk population.

  9. 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

  10. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques

    OpenAIRE

    2007-01-01

    Monocytes participate critically in atherosclerosis. There are 2 major subsets expressing different chemokine receptor patterns: CCR2+CX3CR1+Ly-6Chi and CCR2–CX3CR1++Ly-6Clo monocytes. Both C-C motif chemokine receptor 2 (CCR2) and C-X3-C motif chemokine receptor 1 (CX3CR1) are linked to progression of atherosclerotic plaques. Here, we analyzed mouse monocyte subsets in apoE-deficient mice and traced their differentiation and chemokine receptor usage as they accumulated within atherosclerotic...

  11. 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...

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Hanna E Auvinen

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

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

    Directory of Open Access Journals (Sweden)

    Ida Rune

    Full Text Available The importance of the gut microbiota (GM in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD, and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/- mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis

  15. 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

  16. 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……

  17. Vulnerable Plaque Detection and Quantification with Gold Particle–Enhanced Computed Tomography in Atherosclerotic Mouse Models

    Directory of Open Access Journals (Sweden)

    David De Wilde

    2015-06-01

    Full Text Available Recently, an apolipoprotein E–deficient (ApoE−/− mouse model with a mutation (C1039G+/− in the fibrillin-1 (Fbn1 gene (ApoE−/−Fbn1C1039G+/− mouse model was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE−/− mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle–enhanced micro–computed tomography (microCT scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries. Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE−/−Fbn1C1039G+/− compared to the ApoE−/− mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle–enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.

  18. Genome-wide analysis of LXRα activation reveals new transcriptional networks in human atherosclerotic foam cells.

    Science.gov (United States)

    Feldmann, Radmila; Fischer, Cornelius; Kodelja, Vitam; Behrens, Sarah; Haas, Stefan; Vingron, Martin; Timmermann, Bernd; Geikowski, Anne; Sauer, Sascha

    2013-04-01

    Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To pursue the hypothesis that ligand-based modulation of the nuclear receptor LXRα is crucial for cell homeostasis during atherosclerotic processes, we analysed genome-wide the action of LXRα in foam cells and macrophages. By integrating chromatin immunoprecipitation-sequencing (ChIP-seq) and gene expression profile analyses, we generated a highly stringent set of 186 LXRα target genes. Treatment with the nanomolar-binding ligand T0901317 and subsequent auto-regulatory LXRα activation resulted in sequence-dependent sharpening of the genome-binding patterns of LXRα. LXRα-binding loci that correlated with differential gene expression revealed 32 novel target genes with potential beneficial effects, which in part explained the implications of disease-associated genetic variation data. These observations identified highly integrated LXRα ligand-dependent transcriptional networks, including the APOE/C1/C4/C2-gene cluster, which contribute to the reversal of cholesterol efflux and the dampening of inflammation processes in foam cells to prevent atherogenesis.

  19. 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.

  20. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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 ...

  9. Anti-inflammatory Diets.

    Science.gov (United States)

    Sears, Barry

    2015-01-01

    Chronic disease is driven by inflammation. This article will provide an overview on how the balance of macronutrients and omega-6 and omega-3 fatty acids in the diet can alter the expression of inflammatory genes. In particular, how the balance of the protein to glycemic load of a meal can alter the generation of insulin and glucagon and the how the balance of omega-6 and omega-3 fatty acids can effect eicosanoid formation. Clinical results on the reduction of inflammation following anti-inflammatory diets are discussed as well as the molecular targets of anti-inflammatory nutrition. To overcome silent inflammation requires an anti-inflammatory diet (with omega-3s and polyphenols, in particular those of Maqui). The most important aspect of such an anti-inflammatory diet is the stabilization of insulin and reduced intake of omega-6 fatty acids. The ultimate treatment lies in reestablishing hormonal and genetic balance to generate satiety instead of constant hunger. Anti-inflammatory nutrition, balanced 40:30:30 with caloric restriction, should be considered as a form of gene silencing technology, in particular the silencing of the genes involved in the generation of silent inflammation. To this anti-inflammatory diet foundation supplemental omega-3 fatty acids at the level of 2-3 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day should be added. Finally, a diet rich in colorful, nonstarchy vegetables would contribute adequate amounts of polyphenols to help not only to inhibit nuclear factor (NF)-κB (primary molecular target of inflammation) but also activate AMP kinase. Understanding the impact of an anti-inflammatory diet on silent inflammation can elevate the diet from simply a source of calories to being on the cutting edge of gene-silencing technology.

  10. Omega-3 Fatty Acids and Inflammatory Processes

    Directory of Open Access Journals (Sweden)

    Philip C. Calder

    2010-03-01

    Full Text Available Long chain fatty acids influence inflammation through a variety of mechanisms; many of these are mediated by, or at least associated with, changes in fatty acid composition of cell membranes. Changes in these compositions can modify membrane fluidity, cell signaling leading to altered gene expression, and the pattern of lipid mediator production. Cell involved in the inflammatory response are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the n-3 fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these often have differing properties from those of arachidonic acid-derived eicosanoids. EPA and DHA give rise to newly discovered resolvins which are anti-inflammatory and inflammation resolving. Increased membrane content of EPA and DHA (and decreased arachidonic acid content results in a changed pattern of production of eicosanoids and resolvins. Changing the fatty acid composition of cells involved in the inflammatory response also affects production of peptide mediators of inflammation (adhesion molecules, cytokines etc.. Thus, the fatty acid composition of cells involved in the inflammatory response influences their function; the contents of arachidonic acid, EPA and DHA appear to be especially important. The anti-inflammatory effects of marine n-3 PUFAs suggest that they may be useful as therapeutic agents in disorders with an inflammatory component.

  11. Detection of five periodontal pathogens in coronary atherosclerotic plaque%牙周致病菌在动脉粥样硬化斑块中的检测

    Institute of Scientific and Technical Information of China (English)

    侯秀丽; 梁平; 张源明; 木拉提; 艾斯卡尔; 艾克拜尔; 闰跃斌

    2011-01-01

    目的 检测冠状动脉粥样硬化斑块中的5种特异性牙周致病菌.方法 收集101例行冠状动脉搭桥手术患者的动脉粥样硬化斑块标本,采用Chelex-100法提取冠状动脉粥样硬化斑块中的DNA,并通过PCR分别检测动脉粥样硬化斑块中的牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg)、伴放线放线杆菌(Actinobacillus actinomycetemcomitans,Aa)、具核梭杆菌(Fusobacterium nucleatum,Fn)、中间普氏菌(Prevotella intermedia,Pi)、福赛斯坦纳菌(Tannerella forsythensis,Tf)5种牙周特异性致病菌.结果 101例患者动脉粥样硬化斑块中牙龈卟啉单胞菌(Pg)的检出率为31%,福赛斯坦纳菌(Tf)为42%,中间普氏菌(Pi)为26%,具核梭杆菌(Fn)为21%,伴放线放线杆菌(Aa)为23%.这几种细菌的PCR产物通过测序,结果与GenBank数据库中的序列进行比对同源性达99%~100%.结论 牙周致病菌在冠心病的发生、发展中可能发挥着一定作用,考虑慢性牙周炎与冠心病之间有一定的相关性.%Objective To detect five periodontal pathogenic bacteria in coronary atherosclerotic plaques.Methods Atherosclerotic plaque specimens were obtained from 101 patients who scheduled for coronary artery bypass graft surgery.The bacteria DNA was obtained from coronary atherosclerotic plaques using the chelex-100 method.The extracted DNA were examined by PCR.Results Within the 101 pieces of atherosclerotic plaque samples Porphyromonas gingivalis( Pg,31% ),Tannerella forsythensis(Tf,42% ),Prevotella intermedia( Pi,26% ),Fusobacterium nucleatum( Fn,21% ),Actinobacillus actinomycetemcomitans( Aa,23% ).PCR products were sequenced and were compared with GenBank sequences,the homology was 99%-100%.Conclusion Periodontitis might affect the development of atherosclerosis and there is a correlation between coronary heart disease and chronic periodontitis.

  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. 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 Holm; 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...

  14. Low TLR7 gene expression in atherosclerotic plaques is associated with major adverse cardio- and cerebrovascular events

    DEFF Research Database (Denmark)

    Karadimou, Glykeria; Folkersen, Lasse; Berg, Martin;

    2016-01-01

    Aims: Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome an...

  15. 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

  16. The anti-atherosclerotic effect of tanshinol borneol ester using fecal metabolomics based on liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Jia, Pu; Wang, Shixiang; Xiao, Chaoni; Yang, Lumeng; Chen, Yongyong; Jiang, Wei; Zheng, Xiaopu; Zhao, Guifang; Zang, Weijin; Zheng, Xiaohui

    2016-02-07

    Tanshinol borneol ester (DBZ) is a novel experimental compound that consists of two chemical structural units from danshensu and borneol. It exhibits efficacious anti-ischemic and anti-atherosclerosis activities in rats. A fecal metabolomics based on Liquid Chromatography-Mass Spectrometry combined with clinical histopathology and blood lipid estimation was employed to assess the efficacy and the metabolic changes caused by administration of DBZ in atherosclerotic rats. There were the typical pathological features of atherosclerosis and significantly increased levels of TC, TG and LDL-C in the atherosclerotic rat group. Nevertheless, atherosclerotic rats administered both DBZ (at a dose of 40 mg kg(-1)) and simvastatin (at a dose of 20 mg kg(-1)) showed good therapeutic effects. The results of the metabolomics studies showed that 55 differential metabolites such as sebacic acid, enterodiol, nonanedioic acid, dodecanedioic acid, cholic acid, 13(S)-HPODE, deoxycholic acid, some phosphatidylglycerol and phosphatidic acids were found, indicating that abnormal metabolism occurred in the pathways of fatty acid oxidation, linoleic acid metabolism, bile acid biosynthesis and glycerophospholipid metabolism in atherosclerotic rats. Compared to those in the model group, the contents of 41 differential metabolites showed a tendency to recover to a healthy level after DBZ administration. Metabolomics studies suggested that DBZ exhibited good treatment efficacy against atherosclerosis by adjusting disturbed metabolic pathways related to atherosclerosis. This study could provide an experimental basis for DBZ's application to act as a candidate drug with anti-atherosclerosis activity.

  17. Application of IR and NIR fiber optic imaging in thermographic and spectroscopic diagnosis of atherosclerotic vulnerable plaques: preliminary experience

    Science.gov (United States)

    Naghavi, Morteza; Khan, Tania; Gu, Bujin; Soller, Babs R.; Melling, Peter; Asif, Mohammed; Gul, Khawar; Madjid, Mohammad; Casscells, S. W.; Willerson, James T.

    2000-12-01

    Despite major advances in cardiovascular science and technology during the past three decades, approximately half of all myocardial infarctions and sudden deaths occur unexpectedly. It is widely accepted that coronary atherosclerotic plaques and thrombotic complications resulting from their rupture or erosion are the underlying causes of this major health problem. The majority of these vulnerable plaques exhibit active inflammation, a large necrotic lipid core, a thin fibrous cap, and confer a stenosis of less than 70%. These lesions are not detectable by stress testing or coronary angiography. Our group is exploring the possibility of a functional classification based on physiological variables such as plaque temperature, pH, oxygen consumption, lactate production etc. We have shown that heat accurately locates the inflamed plaques. We also demonstrated human atherosclerotic plaques are heterogeneous with regard to pH and hot plaques and are more likely to be acidic. To develop a nonsurgical method for locating the inflamed plaques, we are developing both IR fiber optic imaging and NIR spectroscopic systems in our laboratory to detect hot and acidic plaque in atherosclerotic arterial walls. Our findings introduce the possibility of an isolated/combined IR and NIR fiber optic catheter that can bring new insight into functional assessment of atherosclerotic plaque and thereby detection of active and inflamed lesions responsible for heart attacks and strokes.

  18. Microvessel Density But Not Neoangiogenesis Is Associated with (18)F-FDG Uptake in Human Atherosclerotic Carotid Plaques

    DEFF Research Database (Denmark)

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

    2011-01-01

    Introduction: The vulnerable atherosclerotic lesion exhibits the proliferation of neovessels and inflammation. The imaging modality 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18FDG-PET) is considered for the identification of vulnerable plaques. Purpose: The purpose of this study...

  19. 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

  20. 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...

  1. High-resolution imaging of human atherosclerotic carotid plaques with micro(18)F-FDG PET scanning exploring plaque vulnerability

    NARCIS (Netherlands)

    Masteling, Marleen G.; Zeebregts, Clark J.; Tio, Rene A.; Breek, Jan-Cees; Tietge, Uwe J. F.; de Boer, Jan Freark; Glaudemans, Andor W. J. M.; Dierckx, Rudi A. J. O.; Boersma, Hendrikus H.; Slart, Riemer H. J. A.

    2011-01-01

    FDG-PET can be used to identify vulnerable plaques in atherosclerotic disease. Clinical FDG-PET camera systems are restricted in terms of resolution for the visualization of detailed inflammation patterns in smaller vascular structures. The aim of the study is to evaluate the possible added value of

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

    Directory of Open Access Journals (Sweden)

    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.

  3. MiR-181b Antagonizes Atherosclerotic Plaque Vulnerability Through Modulating Macrophage Polarization by Directly Targeting Notch1.

    Science.gov (United States)

    An, Tian-Hui; He, Quan-Wei; Xia, Yuan-Peng; Chen, Sheng-Cai; Baral, Suraj; Mao, Ling; Jin, Hui-Juan; Li, Ya-Nan; Wang, Meng-Die; Chen, Jian-Guo; Zhu, Ling-Qiang; Hu, Bo

    2016-10-08

    Atherosclerotic plaque vulnerability is the major cause for acute stroke and could be regulated by macrophage polarization. MicroRNA-181b (miR-181b) was involved in macrophage differential. Here, we explore whether miR-181b could regulate atherosclerotic plaque vulnerability by modulating macrophage polarization and the underline mechanisms. In acute stroke patients with atherosclerotic plaque, we found that the serum level of miR-181b was decreased. Eight-week apolipoprotein E knockout (ApoE(-/-)) mice were randomly divided into three groups (N = 10): mice fed with normal saline (Ctrl), mice fed with high-fat diet, and tail vein injection with miRNA agomir negative control (AG-NC)/miR-181b agomir (181b-AG, a synthetic miR-181b agonist). We found that the serum level of miR-181b in AG-NC group was lower than that in Ctrl group. Moreover, 181b-AG could upregulate miR-181b expression, reduce artery burden and attenuate atherosclerotic plaque vulnerability by modulating macrophage polarization. In RAW264.7 cells treated with oxidized low-density lipoprotein (ox-LDL), we found miR-181b could reverse the function of ox-LDL on M1/M2 markers at both mRNA and protein levels. Furthermore, by employing luciferase reporter assay, we found that Notch1 was a direct target of miR-181b and could be regulated by miR-181b in vivo and in vitro. Finally, inhibition of Notch1 could abolish the function of downregulating miR-181b on increasing M2 phenotype macrophages. Our study demonstrates that administration of miR-181b could reduce atherosclerotic plaque vulnerability partially through modulating macrophage phenotype by directly targeting Notch1.

  4. 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.

  5. 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.

  6. 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)

  7. Inflammatory Manifestations of Lymphedema

    Directory of Open Access Journals (Sweden)

    Catherine L. Ly

    2017-01-01

    Full Text Available Lymphedema results from lymphatic insufficiency leading to a progressive inflammatory process that ultimately manifests as discomfort, recurrent infections, and, at times, secondary malignancy. Collectively, these morbidities contribute to an overall poor quality of life. Although there have been recent advances in microsurgical interventions, a conservative palliative approach remains the mainstay of treatment for this disabling disease. The absence of a cure is due to an incomplete understanding of the pathophysiological changes that result in lymphedema. A histological hallmark of lymphedema is inflammatory cell infiltration and recent studies with animal models and clinical biopsy specimens have suggested that this response plays a key role in the pathology of the disease. The purpose of this report is to provide an overview of the ongoing research in and the current understanding of the inflammatory manifestations of lymphedema.

  8. Inflammatory Manifestations of Lymphedema

    Science.gov (United States)

    Ly, Catherine L.; Kataru, Raghu P.; Mehrara, Babak J.

    2017-01-01

    Lymphedema results from lymphatic insufficiency leading to a progressive inflammatory process that ultimately manifests as discomfort, recurrent infections, and, at times, secondary malignancy. Collectively, these morbidities contribute to an overall poor quality of life. Although there have been recent advances in microsurgical interventions, a conservative palliative approach remains the mainstay of treatment for this disabling disease. The absence of a cure is due to an incomplete understanding of the pathophysiological changes that result in lymphedema. A histological hallmark of lymphedema is inflammatory cell infiltration and recent studies with animal models and clinical biopsy specimens have suggested that this response plays a key role in the pathology of the disease. The purpose of this report is to provide an overview of the ongoing research in and the current understanding of the inflammatory manifestations of lymphedema. PMID:28106728

  9. The Immunological Basis of Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Francesca A. R. Silva

    2016-01-01

    Full Text Available Inflammatory bowel diseases (IBDs are chronic ailments, Crohn’s disease and ulcerative colitis being the most important. These diseases present an inflammatory profile and they differ according to pathophysiology, the affected area in the gastrointestinal tract, and the depth of the inflammation in the intestinal wall. The immune characteristics of IBD arise from abnormal responses of the innate and adaptive immune system. The number of Th17 cells increases in the peripheral blood of IBD patients, while Treg cells decrease, suggesting that the Th17/Treg proportion plays an important role in the development and maintenance of inflammation. The purpose of this review was to determine the current state of knowledge on the immunological basis of IBD. Many studies have shown the need for further explanation of the development and maintenance of the inflammatory process.

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

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    Veronika A. Myasoedova

    2016-08-01

    Full Text Available 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

  11. 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.

  12. 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.

  13. Radioiodine Therapy Does Not Change the Atherosclerotic Burden of the Carotid Arteries

    DEFF Research Database (Denmark)

    la Cour, Jeppe Lerche; Andersen, Ulrik Bjørn; Sørensen, Christian Hjort

    2016-01-01

    of cerebrovascular events has been reported after radioiodine therapy. This study aimed to examine whether atherosclerosis develops early or late after radioiodine therapy of benign thyroid disease. METHOD: Patients treated for benign thyroid disorders (nontoxic goiter, adenoma, and hyperthyroidism) were examined...... with ultrasound for the main outcome, carotid intima media thickness (CIMT), and for plaque presence (plaque presence only in late damage). Signs of early damage from radioiodine were studied in 39 radioiodine-treated patients, who were examined before treatment and at 1, 3, 6, and 12 months after treatment. Late...... were adjusted for age, sex, cholesterol, smoking status, known atherosclerotic disease, and body mass index. RESULTS: No changes in CIMT were found in the patients followed prospectively for one year after treatment with radioactive iodine for benign thyroid disease (p = 0.58). In the study on late...

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

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    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.

  15. 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...... 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......Hg; P = 0.008, respectively), and serum apolipoprotein (apo) A-1 concentration was lower (1.30 (1.20-1.37) vs. 1.42 (1.36-1.47) milligrams; P = 0.02) in comparison with the normoalbuminuric group. Furthermore, serum HDL-cholesterol concentration tended to be lower, whereas body weight, body mass index...

  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. 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.

  18. 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

    correlate with UAER in regression analyses. It is concluded that the haemostatic balance is unaltered in healthy subjects with microalbuminuria. It is unlikely that a prothrombotic state is present as an intermedial factor early in a causal chain between microalbuminuria and atherosclerotic vascular disease....... with a shift of the haemostatic balance in prothrombotic direction. The following haemostatic factors were measured in two representative groups of clinically healthy subjects, 28 with microalbuminuria (UAER of 6.6-150 micrograms/min) and 60 age- and sex-matched controls with normoalbuminuria (UAER ....6 micrograms/min): Coagulation factors: blood platelet count and mean volume, plasma Factor VII antigen concentration and coagulant activity, and plasma concentrations of prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinogen, and fibrinopeptide A; fibrinolytic and endothelial factors...

  19. Laryngeal inflammatory myofibroblastic tumor.

    Science.gov (United States)

    Girardi, Fábio M; Fontana, Ciro W; Kroef, Ricardo G; Barra, Marinez B; Detânico, Felipe O; Herter, Nilton T

    2014-12-01

    Inflammatory myofibroblastic tumor seldom involves the larynx, as only about 50 to 60 cases have been described in the literature. Even though these tumors are often not aggressive, they have the potential for invasion and local recurrence. We describe the case of a 27-year-old man who was admitted to an emergency department with signs of upper airway obstruction secondary to an obstructive mass. Histology identified the mass as an inflammatory myofibroblastic tumor of the subglottis. The patient underwent an emergency tracheotomy followed by a partial laryngectomy. During 14 months of follow-up, he remained free of active disease.

  20. Acquired inflammatory demyelinating neuropathies.

    Science.gov (United States)

    Ensrud, E R; Krivickas, L S

    2001-05-01

    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  1. Atherosclerotic plaque component segmentation in combined carotid MRI and CTA data incorporating class label uncertainty.

    Directory of Open Access Journals (Sweden)

    Arna van Engelen

    Full Text Available Atherosclerotic plaque composition can indicate plaque vulnerability. We segment atherosclerotic plaque components from the carotid artery on a combination of in vivo MRI and CT-angiography (CTA data using supervised voxelwise classification. In contrast to previous studies the ground truth for training is directly obtained from 3D registration with histology for fibrous and lipid-rich necrotic tissue, and with μCT for calcification. This registration does, however, not provide accurate voxelwise correspondence. We therefore evaluate three approaches that incorporate uncertainty in the ground truth used for training: I soft labels are created by Gaussian blurring of the original binary histology segmentations to reduce weights at the boundaries between components, and are weighted by the estimated registration accuracy of the histology and in vivo imaging data (measured by overlap, 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, fibrous and lipid-rich necrotic tissue, using linear discriminant (LDC and support vector machine (SVM classification. In addition, the combination of MRI and CTA data was compared to using only one imaging modality. Best results were obtained by LDC and outlier rejection: the volume error per vessel was 0.9±1.0% for calcification, 12.7±7.6% for fibrous and 12.1±8.1% for necrotic tissue, with Spearman rank correlation coefficients of 0.91 (calcification, 0.80 (fibrous and 0.81 (necrotic. While segmentation using only MRI features yielded low accuracy for calcification, and segmentation using only CTA features yielded low accuracy for necrotic tissue, the combination of features from MRI and CTA gave good results for all studied components.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Inhibition of inflammatory arthritis using fullerene nanomaterials.

    Science.gov (United States)

    Dellinger, Anthony L; Cunin, Pierre; Lee, David; Kung, Andrew L; Brooks, D Bradford; Zhou, Zhiguo; Nigrovic, Peter A; Kepley, Christopher L

    2015-01-01

    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.

  8. 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 t...... in the epidemiology of IBD....

  9. Cardiac Valvular Inflammatory Pseudotumor

    Directory of Open Access Journals (Sweden)

    Sathe Pragati A

    2008-09-01

    Full Text Available Abstract Inflammatory pseudotumors are quasineoplastic lesions that occur in the lungs as well as other extrapulmonary sites. The heart is an uncommon site of origin. We report a valvular pseudotumor that produced chronic mitral and aortic regurgitation in an elderly woman.

  10. 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...

  11. Pelvic Inflammatory Disease (PID)

    Science.gov (United States)

    ... the ectopic pregnancy is not diagnosed early. Chronic pelvic pain —PID may lead to long-lasting pelvic pain. Who is at risk of PID? PID can ... lead to pelvic inflammatory disease and infertility. Chronic Pelvic Pain: Persistent pain in the pelvic region that has ...

  12. 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.

  13. 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

  14. Relationship between Plasma Levels of Homocysteine and Pro-Inflammatory Cytokines in Patients with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Ayşe Balkarli

    2016-06-01

    Full Text Available Objective: The aim of the study was to investigate levels of homocysteine (Hcy, folate, vitamin B12, interleukin-6 (IL-6 and Tumor necrosis factor-alpha (TNF-α and to assess relationship between Hcy levels and inflammatory mediators including IL-6 and TNF-α in untreated patients with rheumatoid arthritis (RA. Methods: The study included 55 women including 30 newly diagnosed and untreated female RA patients and 25 age-matched healthy individuals as controls. Results: Erythrocyte sedimentation rate (ESH, C-reactive protein (CRP, IL-6 and TNF-α levels were significantly higher in RA patients than controls (p0.05. There were no significant correlations between Hcy levels and acute phase reactants or inflammatory mediators (p>0.05. Conclusion: Both mediators such as IL-6 and TNF-α and hyper-homocysteinemia are associated with atherosclerotic cardiovascular diseases. There was no significant correlation between Hcy levels and inflammatory mediators, although levels of these molecules were elevated in RA. Both inflammatory mediators and Hcy may cause an increase in athero­sclerotic cardiovascular disorders through diverse pathways. J Clin Exp Invest 2016; 7 (2: 163-167

  15. 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.

  16. 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.

  17. Effects of apple juice on risk factors of lipid profile, inflammation and coagulation, endothelial markers and atherosclerotic lesions in high cholesterolemic rabbits

    Directory of Open Access Journals (Sweden)

    rohani Ali

    2009-10-01

    Full Text Available Abstract Background Atherosclerosis which results from gradual deposition of lipids in medium and large arteries is a leading cause of mortality worldwide. The objective of this study was to determine the effect of apple juice on some risk factors of atherosclerosis and on the development of atherosclerosis in rabbits fed a high-cholesterol diet. Methods Thirty two male rabbits were randomly divided into four groups: normal diet, high cholesterol diet (%1 cholesterol, 1% cholesterol supplemented with 5 ml apple juice (low dose and 1% cholesterol supplemented with 10 ml apple juice (high dose for 2 month. The C-reactive protein (CRP, nitrite, nitrate, fibrinogen, total cholesterol(TC and factor VII were measured before the experiment and by the end of period. At the end of study, fatty streak formation in right and left coronary arteries were determined using Chekanov method in all groups. Results Both doses of apple juice significantly were decreased TC, TG, CRP, fibrinogen, factor VII levels, atherosclerotic lesion in right and left coronary arteries and increased nitrite and nitrate compared to cholesterolemic diet. Also using 10 ml apple juice caused significant reduce in LDL-C and increase HDL-C, but 5 ml apple juice did not change these factors. Significant differences were observed between 5 and 10 ml apple juice groups by LDL-C. No significant difference was found between 5 and 10 ml apple juice groups with regard to CRP, nitrite, nitrate, fibrinogen, factor VII, TG, HDL-C and TC concentrations. Conclusion Apple juice can effectively prevent the progress of atherosclerosis. This is likely due to antioxidant and anti-inflammatory effect of apple juice.

  18. Effects of ginkgo biloba extract on the expressions of IL-1β, TNF-α,IL-10 and IL-10R in heart of atherosclerotic rats

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

    Objective:To study whether the anti-AS effect of ginkgo biloba extract (GbE) was related with inhibitory effects on the expression of IL-1β, TNF-α and up-regulation of IL-10 and IL-10R in the heart of atherosclerotic (AS)rats. Methods:The experimental model of AS rats were established by intraperitioneal injection of vitamin D3 with high fat and cholesterol diet. All rats were divided into 3 groups: control,AS and GbE. GbE (100 mg/kg) was administered to rats by ig. After 8 weeks, the expression of IL-1β, TNF-α, IL-10, and IL-10R in the heart of AS rats were detected by enzyme-linked immunosorbant assay, reverse transcriptase polymerasechain reaction and Western blotting. Results:The protein and mRNA expressions of IL-1β,TNF-α,IL-10 and IL-10R were markedly higher in AS group than those in control group (P<0.01). The protein and mRNA expressions of IL-1β and TNF-α were markedly lower in GbE group than those in AS group; while the protein and mRNA expressions of IL-10 and IL-10R were markedly higher in GbE group than those in AS group (P<0.01). Conclusion:GbE has significant inhibitory effects on proinflammatory cytokine IL-1β,TNF-α. The up-regulation of anti-inflammatory cytokine IL-10,IL-10R that may be partially responsible for its anti-AS effects.

  19. 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...

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. Quantitative evaluation of atherosclerotic plaques using cross-polarization optical coherence tomography, nonlinear, and atomic force microscopy

    Science.gov (United States)

    Gubarkova, Ekaterina V.; Kirillin, Mikhail Yu.; Dudenkova, Varvara V.; Timashev, Peter S.; Kotova, Svetlana L.; Kiseleva, Elena B.; Timofeeva, Lidia B.; Belkova, Galina V.; Solovieva, Anna B.; Moiseev, Alexander A.; Gelikonov, Gregory V.; Fiks, Ilya I.; Feldchtein, Felix I.; Gladkova, Natalia D.

    2016-12-01

    A combination of approaches to the image analysis in cross-polarization optical coherence tomography (CP OCT) and high-resolution imaging by nonlinear microscopy and atomic force microscopy (AFM) at the different stages of atherosclerotic plaque development is studied. This combination allowed us to qualitatively and quantitatively assess the disorganization of collagen in the atherosclerotic arterial tissue (reduction and increase of CP backscatter), at the fiber (change of the geometric distribution of fibers in the second-harmonic generation microscopy images) and fibrillar (violation of packing and different nature of a basket-weave network of fibrils in the AFM images) organization levels. The calculated CP channel-related parameters are shown to have a statistically significant difference between stable and unstable (also called vulnerable) plaques, and hence, CP OCT could be a potentially powerful, minimally invasive method for vulnerable plaques detection.

  5. Use of endovascular stents in atherosclerotic renovascular stenosis: blood pressure and renal function changes in hypertensive patients.

    Science.gov (United States)

    Tagle, Rodrigo; Acevedo, Monica; Xu, Meng; Pohl, Marc; Vidt, Donald

    2007-08-01

    Atherosclerotic renal artery stenosis may result in hypertension and ischemic nephropathy. Renal artery endovascular stenting has emerged as current therapy; however, the percentage of patients who benefit from this procedure is still not well established. The authors studied 116 hypertensive patients with atherosclerotic renovascular stenosis who underwent successful renal artery stenting for the first time. At 1 year, there was a significant overall decrease in blood pressure in the group after stenting; however, there was no change in renal function. Also, no significant change in the number of antihypertensive drugs was noted. Blood pressure improved in 55% of the patients, worsened in 14%, and remained unchanged in 31%. Renal function improved in 16% of the patients, worsened in 30%, and remained stable in 54%. In relation to blood pressure control, patients with resistant or difficult-to-control hypertension showed the most improvement in blood pressure control after stenting.

  6. [Influenza viruses and atherosclerosis: the role of atherosclerotic plaques in prolonging the persistent form of influenza infection].

    Science.gov (United States)

    Pleskov, V M; Bannikov, A I; Gurevich, V S; Pleskova, Iu V

    2003-01-01

    It was established that viral particles, like low-density lipoproteins (LDLP), when subjected to some modification changes, lost their ability to be internalized by tissue somatic cells and acquired tropism to macrophage cells. The data, obtained by us by using the polymerase chain reaction (PCR) method, made it possible to assert that atherosclerotic plaques, isolated from vessels of patients with ischemic heart disease (IHD) who underwent coronary bypass, contained RNA of the A(HINI) and AH3N3) influenza viruses. Whereas, the vessel portions, undamaged by atherosclerosis, did not contain any genetic substances of influenza viruses. It was for the first time that an experimentally supported understanding was expressed on that the atherosclerotic plaques serve as a "reservoir" for influenza viruses. It is also suggested that the mentioned plaques can be the carriers of influenza viruses for a long time, thus, prolonging the persistent form of influenza infection in the human body.

  7. 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.

  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. Keratoconus: an inflammatory disorder?

    Science.gov (United States)

    Galvis, V; Sherwin, T; Tello, A; Merayo, J; Barrera, R; Acera, A

    2015-07-01

    Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

  10. Rapid noninvasive detection of experimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates

    Science.gov (United States)

    Elmaleh, David R.; Narula, Jagat; Babich, John W.; Petrov, Artiom; Fischman, Alan J.; Khaw, Ban-An; Rapaport, Eliezer; Zamecnik, Paul C.

    1998-01-01

    The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5′)-tetraphosphate) and its analogue 99mTc AppCHClppA for imaging experimental atherosclerotic lesions in New Zealand White rabbits. Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides. After acquiring the final images, the animals were sacrificed, ex vivo images of the aortas were recorded, and biodistribution was measured. 99mTc-Ap4A and 99mTc AppCHClppA accumulated rapidly in atherosclerotic abdominal aorta, and lesions were clearly visible within 30 min after injection in all animals that were studied. Both radiopharmaceuticals were retained in the lesions for 3 hr, and the peak lesion to normal vessel ratio was 7.4 to 1. Neither of the purine analogs showed significant accumulation in the abdominal aorta of normal (control) rabbits. The excised aortas showed lesion patterns that were highly correlated with the in vivo and ex vivo imaging results. The present study demonstrates that purine receptors are up-regulated in experimental atherosclerotic lesions and 99mTc-labeled purine analogs have potential for rapid noninvasive detection of plaque formation. PMID:9435254

  11. Rapid noninvasive detection of experimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates

    OpenAIRE

    1998-01-01

    The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5′...

  12. [A case report of successful surgical management of lower-limb critical ischaemia on the background of femoropopliteal atherosclerotic aneurysms].

    Science.gov (United States)

    Zotov, S P; Shcherbakov, A V; Zaĭtsev, S S; Khomiakova, E Iu; Abramovskaia, N V

    2009-01-01

    Presented herein is a case report of successful surgical management of a male patient presenting with lower-limb critical ischaemia on the background of thrombosis of femoropopliteal atherosclerotic aneurysms and the presence of a necrobiotic process on the stump of the foot. The reconstructive intervention performed resulted in salvation of the extremity, followed by uneventful wound healing on his left foot with complete medical and social rehabilitation of the patient.

  13. A feasibility study of an intravascular imaging antenna to image atherosclerotic plaques in Swine using 3.0 T MRI.

    Directory of Open Access Journals (Sweden)

    Chen Zhang

    Full Text Available To investigate the feasibility of an intravascular imaging antenna to image abdominal aorta atherosclerotic plaque in swine using 3.0T magnetic resonance imaging (MRI.Atherosclerotic model was established in 6 swine. After 8 months, swine underwent an MR examination, which was performed using an intravascular imaging guide-wire, and images of the common iliac artery and the abdominal aorta were acquired. Intravascular ultrasound (IVUS was performed in the right femoral artery; images at the same position as for the MR examination were obtained. The luminal border and external elastic membrane of the targeted arteries were individually drawn in the MR and IVUS images. After co-registering these images, the vessel, lumen, and vessel wall areas and the plaque burden in the same lesions imaged using different modalities were calculated and compared. The diagnostic accuracy of intravascular MR examination in delineating the vessel wall and detecting plaques were analyzed and compared using IVUS.Compared with IVUS, good agreement was found between MRI and IVUS for delineating vessel, lumen, and vessel wall areas and plaque burden (r value: 0.98, 0.95, 0.96 and 0.91, respectively; P<0.001.Compared with IVUS, using an intravascular imaging guide-wire to image deep seated arteries allowed determination of the vessel, lumen and vessel wall areas and plaque size and burden. This may provide an alternative method for detecting atherosclerotic plaques in the future.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Natural Products: Insights into Leishmaniasis Inflammatory Response

    Science.gov (United States)

    Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

    2015-01-01

    Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

  19. Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk

    Science.gov (United States)

    Lin, Zongwei; Ge, Junfeng; Wang, Zhe; Ren, Jianwei; Wang, Xiaowei; Xiong, Hui; Gao, Jing; Zhang, Yan; Zhang, Qunye

    2017-01-01

    The inflammatory responses of vascular endothelial cells (VECs) are critical in the development of many cardio-cerebrovascular diseases. Let-7e is an important regulator of endothelial function and inflammation. However, the effects and mechanisms of let-7e on VECs inflammation have not been studied until recently. Thus, we investigated these issues and found that in addition to proliferation, apoptosis and cell adhesion, let-7e was also implicated in the regulation of inflammatory responses through a complex network, including IκBβ and lncRNA lnc-MKI67IP-3. Let-7e promoted NF-κB activation and translocation to the nucleus by inhibiting its target gene (IκBβ) expression and subsequently increased the expression of inflammatory and adhesion molecules. Meanwhile, lnc-MKI67IP-3 acted as a sponge or competing endogenous RNA (ceRNA) for let-7e, suppressing its pro-inflammatory effects, and let-7e decreased lnc-MKI67IP-3 expression, thereby forming a positive feedback loop to aggravate inflammation. Moreover, let-7e, lnc-MKI67IP-3 and IκBβ were also abnormal in oxLDL-treated VECs and atherosclerotic plaques. The present study revealed let-7e as a pro-inflammatory mediator and a novel regulatory mechanism for the NF-κB pathway through ceRNA crosstalk, comprising let-7e and its target IκBβ and the ceRNA lnc-MKI67IP-3. Thus, this molecule might play important roles in the inflammatory responses of VECs and development of atherosclerosis. PMID:28195197

  20. 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.

  1. SURGICAL PROPHYLAXIS OF ISCHEMIC INSULTS IN PATIENTS WITH ATHEROSCLEROTIC IMPAIRMENT OF CAROTIDS

    Directory of Open Access Journals (Sweden)

    I.E. Poverennova

    2008-03-01

    Full Text Available The results of prophylaxis of acute impairment of a cerebral circulation with the help of carotid endarterectomy (CEAE are considered. There are examined 324 patients with cerebrovascular pathology 132 of them have transferred CEAEand 156 received only conservative therapy. The results of Wyears observation of operated and non operated patients show, that in patients, who were operated, in mostcases the marked signs of impairment of cerebral circulation in ipsilateral hemisphere were not developed. The results of observation over group of patients who were not operated coincide with the average data according to which the patients who have suffered an ischemic insult, have the riskof development of the subsequent insult at a level of 5-9% in a year, and approximately 25-45% of them have a repeated insult during 5 years period after the first insult. The best clinical effect had CEAE, performed in patients with transitional ischemic attacks. CEAE is the main preventive measure in treatment of patients with an atherosclerotic stenosis of carotids. The analysis of the results of the research testifies to the stable and long-term effect of operation.

  2. 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.

  3. 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.

  4. Chlamydia pneumoniae in the atherosclerotic plaques of coronary artery disease patients.

    Directory of Open Access Journals (Sweden)

    Morteza Izadi

    2013-12-01

    Full Text Available An association between Chlamydia pneumoniae (C. pneumoniae and cardiovascular disease has been demonstrated. In this study, we aimed to study this potential relationship in 105 Iranian patients. Coronary artery specimens from 105 Iranian patients undergoing CABG were analyzed by PCR method for C. pneumoniae. Serological evaluation for C. pneumoniae IgG and IgM was performed using ELISA. 53 specimens from mamillary artery were also investigated. C. pneumoniae PCR test result was positive for 23 (21.9% of patients with coronary artery atherosclerosis, but none of the specimens from the mamillary artery was positive for C. pneumoniae when it was evaluated by the PCR (P<0.001. Coronary artery disease patients with and without a history of unstable angina or myocardial infarction were comparable in C. pneumoniae PCR test positive rates (P=0.618. Relevance of IgG and IgM positivity were also studied by correlating it to the study parameters, but no difference was found. CRP was significantly higher in the IgM positive group (P<0.001. A significant proportion of coronary atherosclerotic plaques are infected with C. pneumoniae while no infection was found in the normal mamillary artery specimens. No association was found between acute coronary syndromes and serological and PCR positivity. Further prospective randomized controlled studies with large patient population are needed to confirm our findings.

  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. 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

    -induced atherosclerosis, based on the Göttingen minipig. Using (18)F-FDG PET/MRI the goal was to develop and create a new imaging method in an in vivo animal model for translational studies of atherosclerosis. We used a strategy of multisequence MRI for optimal anatomical imaging of the abdominal aortas of the pigs (n=4......): T1-weighted turbo spin-echo (T1-TSE), T2-weighted turbo spin-echo (T2-TSE) and proton density imaging with and without fat saturation. (18)F-FDG PET emission data were collected from a single bed position of the abdominal aorta in 3D mode for either 10 (n=4) or 10 and 20 minutes (n=2) to measure...... 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...

  7. 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.

  8. Influence of shear stress magnitude and direction on atherosclerotic plaque composition.

    Science.gov (United States)

    Pedrigi, Ryan M; Mehta, Vikram V; Bovens, Sandra M; Mohri, Zahra; Poulsen, Christian Bo; Gsell, Willy; Tremoleda, Jordi L; Towhidi, Leila; de Silva, Ranil; Petretto, Enrico; Krams, Rob

    2016-10-01

    The precise flow characteristics that promote different atherosclerotic plaque types remain unclear. We previously developed a blood flow-modifying cuff for ApoE(-/-) mice that induces the development of advanced plaques with vulnerable and stable features upstream and downstream of the cuff, respectively. Herein, we sought to test the hypothesis that changes in flow magnitude promote formation of the upstream (vulnerable) plaque, whereas altered flow direction is important for development of the downstream (stable) plaque. We instrumented ApoE(-/-) mice (n = 7) with a cuff around the left carotid artery and imaged them with micro-CT (39.6 µm resolution) eight to nine weeks after cuff placement. Computational fluid dynamics was then performed to compute six metrics that describe different aspects of atherogenic flow in terms of wall shear stress magnitude and/or direction. In a subset of four imaged animals, we performed histology to confirm the presence of advanced plaques and measure plaque length in each segment. Relative to the control artery, the region upstream of the cuff exhibited changes in shear stress magnitude only (p < 0.05), whereas the region downstream of the cuff exhibited changes in shear stress magnitude and direction (p < 0.05). These data suggest that shear stress magnitude contributes to the formation of advanced plaques with a vulnerable phenotype, whereas variations in both magnitude and direction promote the formation of plaques with stable features.

  9. 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

  10. Fluorescence lifetime imaging for the characterization of the biochemical composition of atherosclerotic plaques

    Science.gov (United States)

    Phipps, Jennifer; Sun, Yinghua; Saroufeem, Ramez; Hatami, Nisa; Fishbein, Michael C.; Marcu, Laura

    2011-09-01

    This study investigates the ability of a flexible fiberoptic-based fluorescence lifetime imaging microscopy (FLIM) technique to resolve biochemical features in plaque fibrotic cap associated with plaque instability and based solely on fluorescence decay characteristics. Autofluorescence of atherosclerotic human aorta (11 autopsy samples) was measured at 48 locations through two filters, F377: 377/50 and F460: 460/60 nm (center wavelength/bandwidth). The fluorescence decay dynamic was described by average lifetime (τ) and four Laguerre coefficients (LECs) retrieved through a Laguerre deconvolution technique. FLIM-derived parameters discriminated between four groups [elastin-rich (ER), elastin and macrophage-rich (E+M), collagen-rich (CR), and lipid-rich (LR)]. For example, τF377 discriminated ER from CR (R = 0.84); τF460 discriminated E+M from CR and ER (R = 0.60 and 0.54, respectively); LEC-1F377 discriminated CR from LR and E+M (R = 0.69 and 0.77, respectively); P 87% (all cases) and sensitivity as high as 86%. Current results demonstrate for the first time that clinically relevant features (e.g., ratios of lipid versus collagen versus elastin) can be evaluated with a flexible-fiber based FLIM technique without the need for fluorescence intensity information or contrast agents.

  11. Haemodynamic predictors of a penetrating atherosclerotic ulcer rupture using fluid-structure interaction analysis.

    Science.gov (United States)

    D'Ancona, Giuseppe; Amaducci, Andrea; Rinaudo, Antonino; Pasta, Salvatore; Follis, Fabrizio; Pilato, Michele; Baglini, Roberto

    2013-09-01

    We present preliminary data on the flow-induced haemodynamic and structural loads exerted on a penetrating atherosclerotic aortic ulcer (PAU). Specifically, one-way fluid-structure interaction analysis was performed on the aortic model reconstructed from a 66-year-old male patient with a PAU that evolved into an intramural haematoma and rupture of the thoracic aorta. The results show that elevated blood pressure (117 mmHg) and low flow velocity at the aortic wall (0.15 m/s(2)) occurred in the region of the PAU. We also found a low value of time-averaged wall shear stress (1.24 N/m(2)) and a high value of the temporal oscillation in the wall shear stress (oscillatory shear index = 0.13) in the region of the PAU. After endovascular treatment, these haemodynamic parameters were distributed uniformly on the luminal surface of the stent graft. These findings suggest that wall shear stress could be considered one of the major haemodynamic factors indicating the structural fragility of the PAU wall, which ultimately lead to PAU growth and rupture.

  12. 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.

  13. Temporal and quantitative analysis of expression of metalloproteinases (MMPs) and their endogenous inhibitors in atherosclerotic lesions.

    Science.gov (United States)

    Yu, Ying; Koike, Tomonari; Kitajima, Shuji; Liu, Enqi; Morimoto, Masatoshi; Shiomi, Masashi; Hatakeyama, Kinta; Asada, Yujiro; Wang, Ke-Yong; Sasaguri, Yasuyuki; Watanabe, Teruo; Fan, Jianglin

    2008-12-01

    Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of vascular diseases, such as atherosclerosis, plaque rupture and aneurysms. Although several MMPs have been demonstrated in the lesions of atherosclerosis, their expression profiles during the initiation and progression of lesions have not been fully determined. We hypothesized that the expression of various MMPs, along with their endogenous inhibitors, may be differentially regulated dependent upon the lesion progression. Therefore, we made a temporal and quantitative analysis of the mRNA and protein expression of MMPs and tissue inhibitors of metalloproteinases expressed in the different stages of atherosclerotic lesions of rabbits and humans. We found that MMP-1, MMP-12 and MMP-13 expression was nearly absent in the normal arterial wall, but was remarkably increased with lesion progression. Furthermore, the expression of these MMPs in the lesions was closely associated with intimal macrophages and monocyte chemoattractant protein-1 expression, suggesting that the intimal macrophages are the major source of production of these MMPs. MMP-3 and MT1-MMP were also significantly upregulated in the early-stage lesions and fatty streaks compared to the normal aortas of rabbits. Our results indicate that MMP-1, -12, and -13 derived from intimal macrophages may play a pivotal role in both lesion initiation and progression, and therefore are potential therapeutic targets for the treatment of plaque rupture and aneurysm formation.

  14. Automated classification of atherosclerotic plaque from magnetic resonance images using predictive models.

    Science.gov (United States)

    Anderson, Russell W; Stomberg, Christopher; Hahm, Charles W; Mani, Venkatesh; Samber, Daniel D; Itskovich, Vitalii V; Valera-Guallar, Laura; Fallon, John T; Nedanov, Pavel B; Huizenga, Joel; Fayad, Zahi A

    2007-01-01

    The information contained within multicontrast magnetic resonance images (MRI) promises to improve tissue classification accuracy, once appropriately analyzed. Predictive models capture relationships empirically, from known outcomes thereby combining pattern classification with experience. In this study, we examine the applicability of predictive modeling for atherosclerotic plaque component classification of multicontrast ex vivo MR images using stained, histopathological sections as ground truth. Ten multicontrast images from seven human coronary artery specimens were obtained on a 9.4 T imaging system using multicontrast-weighted fast spin-echo (T1-, proton density-, and T2-weighted) imaging with 39-mum isotropic voxel size. Following initial data transformations, predictive modeling focused on automating the identification of specimen's plaque, lipid, and media. The outputs of these three models were used to calculate statistics such as total plaque burden and the ratio of hard plaque (fibrous tissue) to lipid. Both logistic regression and an artificial neural network model (Relevant Input Processor Network-RIPNet) were used for predictive modeling. When compared against segmentation resulting from cluster analysis, the RIPNet models performed between 25 and 30% better in absolute terms. This translates to a 50% higher true positive rate over given levels of false positives. This work indicates that it is feasible to build an automated system of plaque detection using MRI and data mining.

  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. Calibration of the Pooled Cohort Equations for Atherosclerotic Cardiovascular Disease: An Update.

    Science.gov (United States)

    Cook, Nancy R; Ridker, Paul M

    2016-12-06

    The latest guidelines from the American College of Cardiology and American Heart Association, released in fall 2013, provide a long-anticipated update to the recommendations of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). The guidelines incorporate a new risk score for atherosclerotic cardiovascular disease that includes stroke as well as coronary heart disease. After publication, the new pooled cohort equations (PCEs) were evaluated in 15 studies from the United States and Europe, most of which used cohorts that were more contemporary than those used in developing the guidelines. In almost all of these external validation cohorts, the PCEs overestimated the observed risk. This narrative review provides an update of the published reports, an overview of the strengths and weaknesses of these validation efforts, and a discussion of possible reasons for the discrepancies. These issues may be useful in a recalibration process designed to better match predicted and observed risks relevant for current clinical practice.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Olga Papadodima

    2012-01-01

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

  19. Renal angioplasty for atherosclerotic renal artery stenosis: Cardiologist′s perspective

    Directory of Open Access Journals (Sweden)

    A S Gulati

    2013-01-01

    Full Text Available Atherosclerotic renal artery stenosis (ARAS is frequently associated with concomitant coronary and peripheral arterial disease with a significant impact on cardiovascular morbidity and mortality. Renal angioplasty of ARAS is more challenging because of increased incidence of technical failures, complications, and restenosis; while there is barely perceptible control of hypertension and only marginal improvement in renal function. This is because most of the patient population in recent randomized trials had unmanifested or clinically silent renovascular disease. Manifestations of RAS should be looked for and incorporated in the management plan particularly before deciding for revascularization. In the absence of clinical manifestation like renovascular hypertension, ischemic nephropathy, left ventricular failure, or unstable coronary syndromes; mere presence of RAS is analogous to presence of concomitant peripheral arterial disease which increases risk of adverse coronary events. Dormant-RAS in the absence of any manifestations can be managed with masterly inactivity. Chronological sequence of events and clinical condition of the patient help in decision making by identifying progressive renovascular disease. Selecting patients for renal artery stenting who actually will benefit from revascularization shall also decrease the unnecessary complications inherent with any interventional procedure. The present review is an attempt to analyze the current view on the diagnostic and management issues more specifically about the need and rationale behind angioplasty.

  20. Angiogenesis in atherosclerotic plaque obtained from carotid endarterectomy: association between symptomatology and plaque morphology.

    Science.gov (United States)

    Hiyama, Takami; Tanaka, Toshihide; Endo, Shinichi; Komine, Kazumasa; Kudo, Tadashi; Kobayashi, Hiroo; Shiokawa, Yoshiaki

    2010-01-01

    Carotid plaque with hemorrhage leads to cerebral embolism and ischemic stroke. Plaque angiogenesis and angiogenetic factors such as vascular endothelial growth factor (VEGF) are critical in the progression of atherosclerotic carotid plaque and intraplaque hemorrhage. The correlation between plaque angiogenesis and presence of clinical symptoms was studied in 41 specimens obtained during carotid endarterectomy from 20 symptomatic and 21 asymptomatic patients treated for carotid artery stenosis. Histological findings using hematoxylin-eosin and immunohistochemical staining against von Willebrand factor and VEGF were examined. Intraplaque hemorrhage, calcification, necrosis, and invasion of foam cells were frequently observed in the carotid plaques from symptomatic patients compared with asymptomatic patients. Higher microvessel density was found in the carotid plaques with necrosis and invasion of foam cells compared with plaques without necrosis and/or foam cell invasion, and higher expression of VEGF was found from symptomatic patients compared with asymptomatic patents. These results suggest that plaque angiogenesis and higher level of VEGF expression may enhance the progression of ischemic symptoms in patients with carotid artery stenosis. Invasive macrophages in the plaque of symptomatic patients increase levels of VEGF and might enhance plaque angiogenesis and atherosclerosis progression.

  1. Aldehyde-modified proteins as mediators of early inflammation in atherosclerotic disease.

    Science.gov (United States)

    Antoniak, Derrick T; Duryee, Michael J; Mikuls, Ted R; Thiele, Geoffrey M; Anderson, Daniel R

    2015-12-01

    Inflammation is widely accepted to play a major role in atherosclerosis and other cardiovascular diseases. However, the exact mechanism(s) by which inflammation exerts its pathogenic effect remains poorly understood. A number of oxidatively modified proteins have been associated with cardiovascular disease. Recently, attention has been given to the oxidative compound of malondialdehyde and acetaldehyde, two reactive aldehydes known to covalently bind and adduct macromolecules. These products have been shown to form stable malondialdehyde-acetaldehyde (MAA) adducts that are reactive and induce immune responses. These adducts have been found in inflamed and diseased cardiovascular tissue of patients. Antibodies to these adducted proteins are measurable in the serum of diseased patients. The isotypes involved in the immune response to MAA (i.e., IgM, IgG, and IgA) are predictive of atherosclerotic disease progression and cardiovascular events such as an acute myocardial infarction or coronary artery bypass grafting. Therefore, it is the purpose of this article to review the past and current knowledge of aldehyde-modified proteins and their role in cardiovascular disease.

  2. Study of Methionine, Vitamin B12, and Folic Acid Status in Coronary Atherosclerotic Male Patients

    Directory of Open Access Journals (Sweden)

    M Djalali

    2007-09-01

    Full Text Available Background: Increased level of serum homocysteine is one of the risk factor of atherosclerosis. Its production related in some sulfur amino acids such as methionine. Some important cofactors that are involved in metabolic pathways of this amino acid are folate and vitamin B12. We have assessed the status of methionine, folic acid, and vitamin B12 in some coronary atherosclerotic male patients.Methods: In this case-control study, 46 cases of coronary atherosclerosis were selected from male patients aged 37 to 66 years undergoing coronary angiography. Of these, 21 had history of acute myocardial infarction (MI in previous 3 to 36 months and 25 had angina pectoris. The controls were selected from male healthy volunteers. Inclusion criteria for all study participants required that they had no history of diabetes, hypertension, renal, hepatic, or gastrointestinal dis­ease, endocrinal disorders, or psychiatric illness. Nutritional status was assessed using biochemistry methods and estima­tion of nutrient intake. Serum methionine was determined by HPLC methods.Results: Mean serum levels of vitamin B12, and folate, also erythrocyte folate concentration are significantly lower in these patients than in control subjects, but not for methionine. The ratios of serum methionine to vitamin B12 and folate were higher in patients than controls. Vitamin B12 and folate deficiencies, both, were higher in patients than controls.Conclusion: In summary, it is concluded that, despite normal level of serum methionine, coenzymes deficiencies may be one of the factors accounting for atherosclerosis.

  3. 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

  4. 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.

  5. [Inflammatory process, histopathological aspects].

    Science.gov (United States)

    Diébold, J

    1995-01-01

    Inflammation occurs only in conjunctive tissue and is the result of a close cooperation of various cells: blood platelets, endothelial cells, leucocytes, mast cells, fibroblasts. Successive phases can be recognized, the first is characterized by vascular phenomenons defining the acute phase. The second by cellular reactions defining the chronic or granulomatous phase. Various morphological patterns can be recognized in acute or chronic inflammation. In addition, hypersensitivity is responsible of peculiar morphology of the inflammatory response. After tissue necrosis, tissular debris should be eliminated by detersion. Then, a granulation tissue develops representing the first step of the healing, which will not be described here.

  6. Inflammatory bowel disease.

    Science.gov (United States)

    Walsh, Anne; Mabee, John; Trivedi, Kashyap

    2011-09-01

    Crohn disease and ulcerative colitis are the most common forms of inflammatory bowel disease (IBD) likely to be encountered in primary care. Patient-centered care is essential for positive outcomes, and should include long-term continuity with an empathetic primary care provider who can provide skillful coordination of the requisite multidisciplinary approach. Early suspicion of the diagnosis and referral to expert gastroenterologists for confirmation and medical management is essential. Coordinating interdisciplinary consultations, including colorectal surgeons, radiologists, stoma therapists, psychologists, and rheumatologists, in combination with comprehensive patient education, is key to decreasing overall morbidity, mortality, and health care costs associated with IBD.

  7. 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.

  8. 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.

  9. Cholesterol crystals enhance TLR2-and TLR4-mediated pro-inflammatory cytokine responses of monocytes to the proatherogenic oral bacterium Porphyromonas gingivalis

    DEFF Research Database (Denmark)

    Køllgaard, Tania Maria Simonsen; Enevold, Christian; Bendtzen, Klaus

    2017-01-01

    Cholesterol deposits and pro-inflammatory cytokines play an essential role in the pathogenesis of atherosclerosis, a predominant cause of cardiovascular disease (CVD). Epidemiological evidence has linked periodontal disease (PD) with atherosclerotic CVD. Accordingly, viable periodontal pathogens......, tumor necrosis factor (TNF)-α, IL-6, and IL-8. Moreover, CHCs markedly enhanced secretion of IL-1β by monocytes stimulated with the toll-like receptor (TLR) 4 agonist Escherichia coli lipopolysaccharide (LPS), and the TLR2 agonist Staphylococcus aureus lipoteichoic acid. Notably, CHCs also enhanced IL-1...

  10. ω-6 (18:2) and ω-3 (18:3) fatty acids in reconstituted high-density lipoproteins show different functionality of anti-atherosclerotic properties and embryo toxicity.

    Science.gov (United States)

    Park, Ki-Hoon; Kim, Jae-Yong; Choi, Inho; Kim, Jae-Ryong; Cho, Kyung-Hyun

    2015-12-01

    Among unsaturated fatty acids, epidemiologic studies have demonstrated that ω-6 (linoleic acid) and ω-3 (linolenic acid) fatty acids show different associations with risk of cardiovascular disease (CVD), although its molecular mechanisms remain unclear. To determine why consumption of ω-3 fatty acid is associated with lower risk of CVD, we investigated the biological functions of ω-6 (linoleic acid) and ω-3 (linolenic acid) in reconstituted HDL (rHDL) after encapsulation using human cells and zebrafish embryo. Apolipoprotein A-I (apoA-I) is the principal protein behind the beneficial functions of HDL, which include potent anti-oxidant, anti-inflammatory, and anti-atherosclerotic activities in blood. Several rHDLs were synthesized with apoA-I and different molar ratio of ω-6 or ω-3 fatty acid. Both fatty acids showed similar solubility in rHDL up to a molar ratio of 95:5:1:10 (palmitoyloleoyl phosphatidylcholine:cholesterol:apoA-I:fatty acid). Although both rHDL showed similar structural properties and α-helical contents, ω-6-rHDL showed loss of anti-oxidant ability against LDL oxidation. Uptake of acetylated LDL into macrophages was inhibited by ω-3-rHDL but not ω-6-rHDL, suggesting that ω-6-rHDL has higher pro-atherosclerotic activity. ω-3-rHDL showed more enhanced cholesterol efflux activity with less accumulation of triglyceride in the macrophage. ω-6-rHDL caused more senescence in human dermal fibroblast cells with cytotoxicity, while ω-3-rHDL treatment inhibited the senescence. In zebrafish embryo survivability, ω-3-rHDL-injected embryos showed 86±3% survival, whereas ω-6-rHDL-injected ones showed 72±2% survival as well as an elevated inflammatory response in zebrafish embryos. In conclusion, ω-6-rHDL and ω-3-rHDL show different physiological activities in atherosclerosis, inflammation, and cellular senescence.

  11. Quercetin modulates toll-like receptor-mediated protein kinase signaling pathways in oxLDL-challenged human PBMCs and regulates TLR-activated atherosclerotic inflammation in hypercholesterolemic rats.

    Science.gov (United States)

    Bhaskar, Shobha; Helen, A

    2016-12-01

    Toll-like receptors (TLRs) are pattern recognition receptors that have a unique and essential function in innate immunity. The effect of quercetin on TLR-mediated downstream signaling mechanism and its effect on TLR-mediated MAP kinase and Akt pathways were studied in oxLDL-stimulated hPBMCs using specific inhibitors. The pretreatment of hPBMCs with specific TLR inhibitor, CLI-095, decreased the NF-κB nuclear translocation and TNF-α release by oxLDL. When the cells treated with inhibitor and quercetin together, the inhibition was more effective. The specific inhibitor for p38 MAPK, SB203580, reduced the phosphorylated p38 level and decreased the NF-κB activation and TNF-α release by oxLDL-challenged hPBMCs. This inhibitor showed enhanced inhibition when treated with quercetin together. The inhibitors for ERK1/2, PD98059, and for JNK, SP606125, also showed inhibitory effect on NF-κB activation and TNF-α release by oxLDL-simulated hPBMCs. Quercetin supplementation enhanced the inhibition of nuclear translocation of NF-κB and the release of cytokines. TLR4 inhibition study confirmed the downstream signaling mechanism mediated by NF-κB which is involved in the oxLDL-induced inflammatory response, and quercetin suppresses the cytokine, TNF-α release by modulating TLR-NF-κB signaling pathway. In addition to NF-κB signaling pathway, inflammation induced by oxLDL was also related to the activation of p38MAPK, ERK1/2 and JNK, and Akt pathways, and the protective effect of quercetin may be also related to the inhibition of activation of these pathways. Quercetin significantly downregulated the elevated mRNA expression of TLRs and cytokine TNF-α in HCD-fed atherosclerotic rats in vivo. As quercetin possesses inhibition on both TLR-NF-κB signaling pathway and TLR-mediated MAPK pathway, it is evident that it can be used as a therapeutic agent to ameliorate atherosclerotic inflammation. Since quercetin is the major flavonoid and forms the backbone of many other

  12. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    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, expe...... affects can be choreographed and designed intentionally or whether it arises from unpredictable circumstances within urbanity itself....

  13. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    of environmental knowledge production. It uses InfoAmazonia, the databased platform on Amazon rainforests, as an example of affective geo-visualization within information mapping that enhances embodiment in the experience of the information. Amazonia is defined as a digitally created affective (map)space within...

  14. 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.

  15. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

    DEFF Research Database (Denmark)

    Gudbjartsson, Daniel F; Bjornsdottir, Unnur S; Halapi, Eva

    2009-01-01

    Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in ...

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Association between serum 25-hydroxyvitamin D and carotid atherosclerotic plaque in Chinese type 2 diabetic patients

    Science.gov (United States)

    Ding, Ya-Hui; Wei, Tie-Ming; Qian, Lin-Yan; Ma, Yuan; Lao, Di-Bo; Yao, Bin; Pang, Jie

    2017-01-01

    Abstract In this study, we investigated the distribution of vitamin D and its association with carotid atherosclerotic plaque (CP) in Chinese type 2 diabetic (T2D) patients. We performed a cross-sectional study in 210 T2D and 94 age- and gender-matched nondiabetic patients during winter months, by determining serum 25-hydroxyvitamin D (25(OH)D) levels in both diabetic and nondiabetic controls. We carried out measurements of B-mode ultrasonography of carotid arteries in each T2D patient. The 25(OH)D concentration was 26.25 nmol/L among the T2D patients. About 93.3% T2D patients suffered from hypovitaminosis D. First, we found a clear inverse correlation between the 25(OH)D concentration and CP (P confounding factors, we also observed a positive correlation between low levels of 25(OH)D in T2D patients with CP, when the following parameters were measured: old age (odds ratio [OR] = 2.533, P = 0.013); smoking (OR = 3.872, P = 0.001); and high level of low-density lipoprotein (LDL) cholesterol (OR = 2.776, P = 0.009). Thus, we concluded that high prevalence of hypovitaminosis D exists in Chinese T2D patients. Further, we found a significant association between low concentration of serum 25(OH)D and the existence of high body mass index, and high circulating LDL to be substantially positive predictors of patients with CP in T2D. PMID:28353575

  4. Delineation of atherosclerotic plaque using subharmonic imaging filtering techniques and a commercial intravascular ultrasound system.

    Science.gov (United States)

    Sridharan, Anush; Eisenbrey, John R; Machado, Priscilla; deMuinck, Ebo D; Doyley, Marvin M; Forsberg, Flemming

    2013-01-01

    The ability to delineate atherosclerotic plaque from the surrounding tissue using custom-developed subharmonic imaging (SHI) digital filtering techniques was investigated in vivo using a commercially available system. Atherosclerosis was induced in the aorta of two Watanabe Heritable Hyperlipidemic rabbits following which injections of an ultrasound contrast agent (UCA) Definity (Lantheus Medical Imaging, N Billerica, Massachusetts) were administered. Imaging was performed using a Galaxy intravascular ultrasound (IVUS) scanner (Boston Scientific, Natick, Massachusetts) equipped with an Atlantis® SR Pro Imaging Catheter (Boston Scientific). Four preliminary band-pass filters were designed to isolate the subharmonic signal (from surrounding tissue) and applied to the radio-frequency (RF) data. Preliminary filter performances were compared in terms of vessel-tissue contrast-to-tissue ratio (CTR) and visual examination. Based on preliminary results, a subharmonic adaptive filter and a stopband (SB) filter were designed and applied to the RF data. Images were classified as fundamental, SHI, and SB. Four readers performed qualitative analysis of 168 randomly selected images (across all three imaging modes). The images were scored for overall image quality, image noise, plaque visualization, and vessel lumen visualization. A Wilcoxon signed-rank test was used to compare the scores followed by intraclass correlation (ICC) evaluation. Quantitative analysis was performed by calculating the CTRs for the vessel-to-plaque and vessel-to-tissue (compared using a paired student's t test). Qualitative analysis showed SHI and SB to have significantly less image noise relative to the fundamental mode (p < 0.001). Fundamental mode scored significantly higher than SHI and SB for the remaining three categories. ICC showed mixed results among reader evaluation for delineation of plaque. However, quantitatively, SHI produced the best vessel-plaque CTR.

  5. Ultrastructure of the human aortic fibrolipid lesion. Formation of the atherosclerotic lipid-rich core.

    Science.gov (United States)

    Bocan, T. M.; Schifani, T. A.; Guyton, J. R.

    1986-01-01

    The formation of the atherosclerotic lipid-rich core has been elucidated by electron microscopy of the core region in small, raised fibrolipid lesions. The relationship among lipid deposits, extracellular matrix, and cells found in distinct regions of the fibrolipid lesion was examined. Extracellular lipid droplets, verified by osmium-thiocarbohydrazide-osmium staining, made up approximately 40% of the lipid-rich core volume. The lipid droplets were often found distinctly associated with elastin and/or collagen; these associations were dependent upon the location examined within or near the lipid-rich core. Within areas of intense extracellular lipid deposits, crystalline clefts suggesting cholesterol monohydrate were observed. Stereologic analysis of the lipid-rich core components revealed marked reductions in the volume fractions of cells, reticular ground substance, and basement membrane; while the extent of extracellular lipid increased 7-10-fold. Eleven percent or less of lipid in the core region was found within cells, usually smooth muscle cells. Above the core region in the lesion cap, monocyte-macrophage foam cells were prominent. Cellular lipid droplets were much larger (profile diameters sixfold higher) than extracellular droplets. With these data as well as transitional morphologic features at the boundaries of the core region, it is suggested that the abundant extracellular lipid does not derive from cell necrosis, and lipid deposition in association with extracellular matrix constituents is an early event in the development of the lipid-rich core. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:3717297

  6. Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

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    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.

  7. Association of carotid atherosclerotic plaque features with acute ischemic stroke: A magnetic resonance imaging study

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    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.

  8. Detection of Vulnerable Atherosclerotic Plaques in Experimental Atherosclerosis with the USPIO-Enhanced MRI.

    Science.gov (United States)

    Qi, Chun-Mei; Du, Lili; Wu, Wei-Heng; Li, Dong-Ye; Hao, Ji; Gong, Lei; Deng, Liangrong; Zhang, Tao; Zhang, Chao; Zhang, Yu

    2015-11-01

    This study's goal was to assess the diagnostic value of the USPIO-(ultra-small superparamagnetic iron oxide) enhanced magnetic resonance imaging (MRI) in detection of vulnerable atherosclerotic plaques in abdominal aorta in experimental atherosclerosis. Thirty New Zealand rabbits were randomly divided into two groups, Group A and Group B. Each group comprised 15 animals which were fed with high cholesterol diet for 8 weeks and then subjected to balloon-induced endothelial injury of the abdominal aorta. After another 8 weeks, animals in Group B received adenovirus carrying p53 gene that was injected through a catheter into the aortic segments rich in plaques. Two weeks later, all rabbits were challenged with the injection of Chinese Russell's viper ven