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Sample records for underlying atherosclerosis development

  1. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

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    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  2. Effects of Antisense Oligonucleotides against C-Reactive Protein on the Development of Atherosclerosis in WHHL Rabbits

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    Qi Yu

    2014-01-01

    Full Text Available Increased plasma levels of C-reactive protein (CRP are closely associated with cardiovascular diseases, but whether CRP is directly involved in the pathogenesis of atherosclerosis is still under debate. Many controversial and contradictory results using transgenic mice and rabbits have been published but it is also unclear whether CRP lowering can be used for the treatment of atherosclerosis. In the current study, we examined the effects of the rabbit CRP antisense oligonucleotides (ASO on the development of atherosclerosis in WHHL rabbits. CRP ASO treatment led to a significant reduction of plasma CRP levels; however, both aortic and coronary atherosclerotic lesions were not significantly changed compared to those of control WHHL rabbits. These results suggest that inhibition of plasma CRP does not affect the development of atherosclerosis in WHHL rabbits.

  3. A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

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    Juan Lin

    2013-01-01

    Full Text Available Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3−/−;Ldlr−/− and RIP3+/+;Ldlr−/− mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3−/− mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.

  4. The role of risk factors in the development of atherosclerosis

    Czech Academy of Sciences Publication Activity Database

    Frohlich, J.; Dobiášová, Milada; Lear, S.; Lee, K. W. J.

    2001-01-01

    Roč. 38, č. 5 (2001), s. 401-440 ISSN 1040-8363 R&D Projects: GA ČR GV306/96/K220 Institutional research plan: CEZ:AV0Z5011922 Keywords : FERHDL * atherosclerosis * new/emerging risk factors Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.931, year: 2001

  5. Murine Norovirus 4 (MNV-4 Infections Trigger Various Effects on Atherosclerosis Development

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    Rafeezul Mohamed

    2018-05-01

    Full Text Available Murine norovirus (MNV infection can cause morbidity and mortality to immune compromised mice, especially colonies in research laboratory. MNV also can infect and propagates in macrophages and dendritic cells which trigger atherosclerosis development through the accumulation of these cells followed by the formation of foam cells. Recently, MNV-4 infection was associated with an increase in aortic sinus lesion size in LDLR (low-density lipoprotein receptor and ApoE (Apolipoprotein E deficient mice, both are well established mouse models for atherosclerosis research. Therefore, this review is intended to summarize the impacts of MNV infection in these two mouse models of atherosclerosis. The findings from all the related studies are important in understanding the fundamental effect of MNV infection on atherosclerosis development. In addition, this information could provide insight to researchers on the evaluation to eliminate MNV infection in research facility to avoid any unintended effect in their research, particularly in-vivo studies involving mice.

  6. Effects of catechins and caffeine on the development of atherosclerosis in mice.

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    Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

    2017-10-01

    Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

  7. Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

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    Ajla Rahimić Ćatić

    2013-04-01

    Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (PConclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

  8. Hypoxia-Inducible Factor-1α Expression in Macrophages Promotes Development of Atherosclerosis

    DEFF Research Database (Denmark)

    Pedersen, Annemarie Aarup; Pedersen, Tanja X; Junker, Nanna

    2016-01-01

    transplanted with bone marrow from mice with HIF-1α deficiency in the myeloid cells or control bone marrow. The HIF-1α deficiency in myeloid cells reduced atherosclerosis in aorta of the Ldlr(-/-) recipient mice by ≈72% (P=0.006).In vitro, HIF-1α-deficient macrophages displayed decreased differentiation...... to proinflammatory M1 macrophages and reduced expression of inflammatory genes. HIF-1α deficiency also affected glucose uptake, apoptosis, and migratory abilities of the macrophages. CONCLUSIONS: HIF-1α expression in macrophages affects their intrinsic inflammatory profile and promotes development of atherosclerosis....

  9. Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

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    Ajla Rahimić Ćatić

    2013-04-01

    Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (P<0.001, followed by systolic blood pressure (P=0.001, diastolic blood pressure (P=0.003 and glucose blood level (P=0.048.Conclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

  10. Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.

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    Natsume, Midori; Baba, Seigo

    2014-01-01

    Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p cacao polyphenol group (p cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses.

  11. Changes of lysosomes in the earliest stages of the development of atherosclerosis.

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    Bobryshev, Yuri V; Shchelkunova, Tatyana A; Morozov, Ivan A; Rubtsov, Petr M; Sobenin, Igor A; Orekhov, Alexander N; Smirnov, Alexander N

    2013-05-01

    One of hypotheses of atherosclerosis is based on a presumption that the zones prone to the development of atherosclerosis contain lysosomes which are characterized by enzyme deficiency and thus, are unable to dispose of lipoproteins. The present study was undertaken to investigate the characteristics and changes of lysosomes in the earliest stages of the development of atherosclerosis. Electron microscopic immunocytochemistry revealed that there were certain changes in the distribution of CD68 antigen in lysosomes along the 'normal intima-initial lesion-fatty streak' sequence. There were no significant changes found in the key mRNAs encoding for the components of endosome/lysosome compartment in initial atherosclerotic lesions, but in fatty streaks, the contents of EEA1 and Rab5a mRNAs were found to be diminished while the contents of CD68 and p62 mRNAs were increased, compared with the intact tissue. The study reinforces a view that changes occurring in lysosomes play a role in atherogenesis from the very earlier stages of the disease. © 2013 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  12. Thymic Stromal Lymphopoietin Attenuates the Development of Atherosclerosis in ApoE−/− Mice

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    Yu, Kunwu; Zhu, Pengfei; Dong, Qian; Zhong, Yucheng; Zhu, Zhengfeng; Lin, Yingzhong; Huang, Ying; Meng, Kai; Ji, Qingwei; Yi, Guiwen; Zhang, Wei; Wu, Bangwei; Mao, Yi; Cheng, Peng; Zhao, Xiaoqi; Mao, Xiaobo; Zeng, Qiutang

    2013-01-01

    Background Thymic stromal lymphopoietin (TSLP) is a cytokine with multiple effects on the body. For one thing, TSLP induces Th2 immunoreaction and facilitates allergic reaction; for another, it promotes the differentiation of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) and maintains immune tolerance. However, the exact role of TSLP in atherosclerosis remains unknown. Methods and Results In vitro, we examined the phenotype of TSLP‐conditioned bone marrow dendritic cells (TSLP‐DCs) of apolipoprotein E–deficient (ApoE−/−) mice and their capacity to induce the differentiation of Tregs. Our results indicated that TSLP‐DCs obtained the characteristics of tolerogenic dendritic cells and increased a generation of CD4+ latency‐associated peptide (LAP)+ Tregs and nTregs when cocultured with naive T cells. In addition, the functional relevance of TSLP and TSLP‐DCs in the development of atherosclerosis was also determined. Interestingly, we found that TSLP was almost absent in cardiovascular tissue of ApoE−/− mice, and TSLP administration increased the levels of antioxidized low‐density lipoprotein IgM and IgG1, but decreased the levels of IgG2a in plasma. Furthermore, mice treated with TSLP and TSLP‐DCs developed significantly fewer (32.6% and 28.2%, respectively) atherosclerotic plaques in the aortic root compared with controls, along with increased numbers of CD4+LAP+ Tregs and nTregs in the spleen and decreased inflammation in the aorta, which could be abrogated by anti‐TGF‐β antibody. Conclusions Our results revealed a protective role for TSLP in atherosclerosis that is possibly mediated by reestablishing a tolerogenic immune response, which may represent a novel possibility for treatment or prevention of atherosclerosis. PMID:23985377

  13. Atherosclerosis VII

    International Nuclear Information System (INIS)

    Fidge, N.H.; Nestel, P.J.; Flinders Univ., Adelaide

    1986-01-01

    In these proceedings the major themes of the conference have been preserved and comprise epidemiology, lipoproteins, pathogenesis, and clinical, therapeutic and nutritional aspects. The diet-lipidcoronary artery disease hypothesis has been strengthened significantly. Several long-awaited trials, reviewed here, have provided very strong support for the rationale for treating hyperlipidemia. A strategy for the prevention of atherosclerosis was defined at the conference. The genesis of atherosclerosis was shown to be more firmly grounded in the influx of lipoprotein into the arterial wall. The regulation of these processes and the rapid advances made possible by new technology were detailed in several sessions. Important new developments in the clinical area and in pharmacology give promise of greatly improved management of established disease. However, the possibility of mounting large-scale preventive measures in the near future, was given credence in the epidemiology and nutrition workshops. (Auth.)

  14. Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications

    International Nuclear Information System (INIS)

    Basavaraju, Sekhara Rao; Easterly, Clay E.

    2002-01-01

    Radiation therapy while important in the management of several diseases, is implicated in the causation of atherosclerosis and other cardiovascular complications. Cancer and atherosclerosis go through the same stages of initiation, promotion, and complication, beginning with a mutation in a single cell. Clinical observations before the 1960s lead to the belief that the heart is relatively resistant to the doses of radiation used in radiotherapy. Subsequently, it was discovered that the heart is sensitive to radiation and many cardiac structures may be damaged by radiation exposure. A significantly higher risk of death due to ischemic heart disease has been reported for patients treated with radiation for Hodgkin's disease and breast cancer. Certain cytokines and growth factors, such as TGF-β1 and IL-1 β, may stimulate radiation-induced endothelial proliferation, fibroblast proliferation, collagen deposition, and fibrosis leading to advanced lesions of atherosclerosis. The treatment for radiation-induced ischemic heart disease includes conventional pharmacological therapy, balloon angioplasty, and bypass surgery. Endovascular irradiation has been shown to be effective in reducing restenosis-like response to balloon-catheter injury in animal models. Caution must be exercised when radiation therapy is combined with doxorubicin because there appears to be a synergistic toxic effect on the myocardium. Damage to endothelial cells is a central event in the pathogenesis of damage to the coronary arteries. Certain growth factors that interfere with the apoptotic pathway may provide new therapeutic strategies for reducing the risk of radiation-induced damage to the heart. Exposure to low level occupational or environmental radiation appears to pose no undue risk of atherosclerosis development or cardiovascular mortality. But, other radiation-induced processes such as the bystander effects, abscopal effects, hormesis, and individual variations in radiosensitivity may be

  15. ApoE-containing HDL and the development of atherosclerosis

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    Zbigniew Zdrojewski

    2015-06-01

    Full Text Available The current state of knowledge about the role of high density lipoproteins (HDL indicates that their anti-atherogenic function is mainly related to the effectiveness of their actions (mostly to the participation in reverse cholesterol transport from tissues to liver rather than the concentration of HDL itself. HDLs are highly heterogeneous in their structure, lipid and protein composition and metabolic pathways and individual HDL subpopulations differ in their biological activity and effectiveness of anti-atherogenic actions. Apolipoproteins play a key role in HDL metabolism, therefore their presence in lipoproteins is one of the main criterion for HDL classification. According to this criterion HDLs containing apolipoprotein E, called HDL-apoE, are distinguished. Although the anti-atherogenic role of apo E has been demonstrated in many scientific reports, understanding of the mechanisms of formation, transformation and the role of HDL-apoE is still the aim of intense research. The results of epidemiological studies are inconclusive; some of them have demonstrated that high HDL- -apoE concentration has been associated with lower risk of developing coronary heart disease (CHD, while other studies have shown that high levels of HDL-apoE has been an independent risk factor for cardiovascular events and positively correlated with other risk factors for CHD.

  16. Vaccination against atherosclerosis

    NARCIS (Netherlands)

    Es, Thomas van

    2009-01-01

    Atherosclerosis, the predominantly underlying pathology of cardiovascular events, is the consequence of lipid deposition in the arterial wall, mostly as consequence of high levels of serum cholesterol. Treatment of atherosclerosis is mainly focused at the reduction of cholesterol levels by lipid

  17. New developments in atherosclerosis: clinical potential of PCSK9 inhibition

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    Giunzioni I

    2015-08-01

    Full Text Available Ilaria Giunzioni, Hagai Tavori Knight Cardiovascular Institute, Center for Preventive Cardiology, Oregon Health and Science University, Portland, OR, USA Abstract: Pro-protein convertase subtilisin/kexin type 9 (PCSK9 is a secreted 692-amino acid protein that binds surface low-density lipoprotein (LDL receptor (LDLR and targets it toward lysosomal degradation. As a consequence, the number of LDLRs at the cell surface is decreased, and LDL-cholesterol (LDL-C clearance is reduced, a phenomenon that is magnified by gain-of-function mutations of PCSK9. In contrast, loss-of-function mutations of PCSK9 result in increased surface LDLR and improved LDL-C clearance. This provides the rationale for targeting PCSK9 in hypercholesterolemic subjects as a means to lower LDL-C levels. Monoclonal antibodies (mAbs against PCSK9 that block its interaction with the LDLR have been developed in the past decade. Two companies have recently received the approval for their anti-PCSK9 mAbs by the US Food and Drug Administration (FDA and the European Medicines Agency (EMA Regeneron/Sanofi, with alirocumab (commercial name – PRALUENT® and, Amgen with evolocumab (commercial name – Repatha™. The introduction of anti-PCSK9 mAbs will provide an alternative therapeutic strategy to address many of the unmet needs of current lipid-lowering therapies, such as inability to achieve goal LDL-C level, or intolerance and aversion to statins. This review will focus on the kinetics of PCSK9, pharmacokinetics and pharmacodynamics of anti-PCSK9 mAbs, and recent data linking PCSK9 and anti-PCSK9 mAbs to cardiovascular events. Moreover, it will highlight the unanswered questions that still need to be addressed in order to understand the physiologic function, kinetics, and dynamics of PCSK9. Keywords: PCSK9, LDLR, monoclonal antibodies, pharmacokinetics, cardiovascular risk

  18. TAP1-deficiency does not alter atherosclerosis development in Apoe-/- mice.

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    Daniel Kolbus

    Full Text Available Antigen presenting cells (APC have the ability to present both extra-cellular and intra-cellular antigens via MHC class I molecules to CD8(+ T cells. The cross presentation of extra-cellular antigens is reduced in mice with deficient Antigen Peptide Transporter 1 (TAP1-dependent MHC class I antigen presentation, and these mice are characterized by a diminished CD8(+ T cell population. We have recently reported an increased activation of CD8(+ T cells in hypercholesterolemic Apoe(-/- mice. Therefore, this study included TAP1-deficient Apoe(-/- mice (Apoe(-/-Tap1(-/- to test the atherogenicity of CD8(+ T cells and TAP1-dependent cross presentation in a hypercholesterolemic environment. As expected the CD8(+ T cell numbers were low in Apoe(-/-Tap1(-/- mice in comparison to Apoe(-/- mice, constituting ~1% of the lymphocyte population. In spite of this there were no differences in the extent of atherosclerosis as assessed by en face Oil Red O staining of the aorta and cross-sections of the aortic root between Apoe(-/-Tap1(-/- and Apoe(-/- mice. Moreover, no differences were detected in lesion infiltration of macrophages or CD3(+ T cells in Apoe(-/-Tap1(-/- compared to Apoe(-/- mice. The CD3(+CD4(+ T cell fraction was increased in Apoe(-/-Tap1(-/- mice, suggesting a compensation for the decreased CD8(+ T cell population. Interestingly, the fraction of CD8(+ effector memory T cells was increased but this appeared to have little impact on the atherosclerosis development.In conclusion, Apoe(-/-Tap1(-/- mice develop atherosclerosis equal to Apoe(-/- mice, indicating a minor role for CD8(+ T cells and TAP1-dependent antigen presentation in the disease process.

  19. The Role of Hypertriglyceridemia in the Development of Atherosclerosis and Endothelial Dysfunction

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    Saki Matsumoto

    2014-03-01

    Full Text Available A hereditary postprandial hypertriglyceridemic rabbit (PHT rabbit is a new dyslipidemic model showing remarkably high plasma triglycerides with only limited elevation of plasma total cholesterol. In PHT rabbits, plasma triglyceride was markedly elevated postprandially compared with healthy Japanese white (JW rabbits. In physiological experiments, the ring preparation of the thoracic aorta was suspended in an organ bath filled with modified Krebs-Henseleit solution, and the developed tension was recorded. Endothelial function was evaluated by acetylcholine-induced vasorelaxation in each preparation with intact endothelium. The acetylcholine-induced endothelium-dependent relaxation was diminished in PHT compared with JW rabbits, suggesting endothelial dysfunction in PHT rabbits. Histological examination was carried out in adipose tissue, liver and aorta. They were fixed in formaldehyde and embedded in paraffin. The tissues were sliced (4 μm and stained using hematoxylin-eosin solution. In the adipose tissue, the visceral fat accumulated, and the size of adipose cells was enlarged in PHT rabbits. The liver of the PHT rabbit was fatty and degenerated. In aorta, increased intimal thickness was observed, suggesting the progression of atherosclerosis in the PHT rabbit. This study suggests the important role of postprandial hypertriglyceridemia in atherosclerosis. By using PHT rabbits, the effects of hypertriglyceridemia on health and diseases could be evaluated precisely.

  20. Phytosterols and atherosclerosis

    DEFF Research Database (Denmark)

    Schrøder, Malene

    Cardiovascular disease (CVD) is the major cause of premature deaths worldwide. Coronary heart disease is the most common CVD, caused by atherosclerosis in the coronary arteries. Atherosclerosis is a multifactorial disease influenced by both genetic and environmental factors. WHO has in 2007 listed...... in its “Guidelines for assessment and management of cardiovascular risk” the following risk factors to influence progressive atherosclerosis: hypertension, abnormal blood lipids, diabetes, unhealthy diet, physical inactivity and smoking. Phytosterols (plant sterols and plant stanols) are known...... their blood cholesterol levels. The aim of this Ph.D. project was to investigate the effects of phytosterols on the development of atherosclerosis in the aorta of heterozygous Watanabe Heritable Hyperlipidemic (WHHL) rabbits. The main advantage of animal studies to human studies in atherosclerosis research...

  1. Immune Response to Lipoproteins in Atherosclerosis

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    Sonia Samson

    2012-01-01

    Full Text Available Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

  2. [As cardioprotective and angiogenic biomarker, can ghrelin predict coronary collateral development and severity of coronary atherosclerosis?

    Science.gov (United States)

    Akboğa, Mehmet Kadri; Taçoy, Gülten; Yılmaz Demirtaş, Canan; Türkoğlu, Sedat; Boyacı, Bülent; Çengel, Atiye

    2017-06-01

    Ghrelin exerts protective effects on cardiovascular system by inhibiting progression of atherosclerosis, supression of vascular inflammation, and stimulating angiogenesis. Thus, the aim of this study was to investigate the effect of serum ghrelin on coronary collateral development and SYNTAX score in patients with severe coronary artery disease. Total of 91 patients who had ≥90% stenosis in at least one major coronary artery were prospectively included in this cross-sectional, observational study. Collateral degree was graded according to Rentrop-Cohen classification. Patients with grade 2 or 3 collateral degree were allocated to Good Collateral Group and patients with grade 0 or 1 collateral degree were included in Poor Collateral Group. Ghrelin and vascular endothelial growth factor A (VEGF-A) levels were measured using radioimmunoassay and ELISA kits. Serum ghrelin and VEGF-A levels were significantly higher in Good Collateral Group. Furthermore, ghrelin level showed significant inverse correlation with SYNTAX score (r=0.348; p=0.001). In multivariable regression analysis, ghrelin (Odds ratio, 1.013; 95% confidence interval, 1.011-1.017; p=0.013), VEGF-A, fasting plasma glucose and presence of chronic total occlusion were independent predictors of good collateral development. In receiver operating characteristic curve analysis, ghrelin value cut-off point of ≥781 pg/mL predicted good collateral development with sensitivity of 73.1% and specificity of 67.7%. Findings suggested that ghrelin has antioxidant and antiinflammatory properties that protect endothelial functions and also stimulate angiogenesis, which results in development of good coronary collateral and inhibition of progression of coronary atherosclerosis.

  3. Concept of Atherosclerosis Velocity: Is It a Better Measure of Cardiovascular Risk?

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    Seyyed Mohammad Reza Kazemi-Bajestani

    2013-09-01

    Full Text Available In most cases atherosclerosis is the underlying cause of vascular diseases, including heart disease and stroke. It is believed that endothelial injury is the earliest change in the artery wall and that this precedes the formation of lesions of atherosclerosis. Recent developments in the field of atherosclerosis have led to a renewed interest in the recognition of the parameter of time in the atherosclerosis process. We believe that the factors determining the time-dependent rate of atherosclerosis progression are important, and it is in this context that we wish to propose for the first time the term “atherosclerosis velocity”. In this review article, we summarize the existing evidence regarding atherosclerosis velocity and discuss the importance of this issue.

  4. Hawthorn (Crataegus pinnatifida Bunge) leave flavonoids attenuate atherosclerosis development in apoE knock-out mice.

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    Dong, Pengzhi; Pan, Lanlan; Zhang, Xiting; Zhang, Wenwen; Wang, Xue; Jiang, Meixiu; Chen, Yuanli; Duan, Yajun; Wu, Honghua; Xu, Yantong; Zhang, Peng; Zhu, Yan

    2017-02-23

    Hawthorn (Crataegus pinnatifida Bunge) leave have been used to treat cardiovascular diseases in China and Europe. Hawthorn leave flavonoids (HLF) are the main part of extraction. Whether hawthorn leave flavonoids could attenuate the development of atherosclerosis and the possible mechanism remain unknown. High-fat diet (HFD) mixed with HLF at concentrations of 5mg/kg and 20mg/kg were administered to apolipoprotein E (apoE) knock out mice. 16 weeks later, mouse serum was collected to determine the lipid profile while the mouse aorta dissected was prepared to measure the lesion area. Hepatic mRNA of genes involved in lipid metabolism were determined. Peritoneal macrophages were collected to study the impact of HLF on cholesterol efflux, formation of foam cell and the expression of ATP binding cassette transporter A1 (ABCA1). Besides, in vivo reverse cholesterol transport (RCT) was conducted. HLF attenuated the development of atherosclerosis that the mean atherosclerotic lesion area in en face aortas was reduced by 23.1% (Pflavonoids can slow down the development of atherosclerosis in apoE knockout mice via induced expression of genes involved in antioxidant activities, inhibition of the foam cell formation and promotion of RCT in vivo, which implies the potential use in the prevention of atherosclerosis. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  5. Atherosclerosis: Hypotheses and theories

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    E. A. Yuryeva

    2014-01-01

    Full Text Available The article gives basic theories of the pathogenesis of atherosclerosis, including inflammatory, cholesterol, lipid, lipoprotein, iron ones, as a result of metabolic syndrome, oxidative stress. In spite of carefully and deeply developed and ongoing elaborated pathogenesis theories, the etiological factors of atherosclerosis remain unknown so far. The age-related aspect of the disease is discussed; atherosclerosis is considered to be a childhood-onset disease that manifests itself at a later age. The authors propose an experimental and clinical evidence-based concept of the common etiology of syndromes of atherosclerosis, namely: the body's endogenous intoxication that is permanent or periodically progressive may be a primary cause of altered conformation of different protein molecules with their higher ability to adsorb the trace elements consolidating the structural changes. This change of proteins diminishes their functions and determines their antigenic properties, which is attended by the development of different pathogenic components in relation to the body's individual features.

  6. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

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    P Padmini S J Khedoe

    Full Text Available COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD, and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L mice.Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study or in week 14, 16, 18 and 20 (chronic study. Inflammatory parameters were measured in bronchoalveolar lavage (BAL and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

  7. Genetic and Pharmacological Inhibition of TREM-1 Limits the Development of Experimental Atherosclerosis

    NARCIS (Netherlands)

    Joffre, Jeremie; Potteaux, Stephane; Zeboudj, Lynda; Boufenzer, Amir; Laurans, Ludivine; Esposito, Bruno; Vandestienne, Marie; de Jager, SCA; Henique, Carole; Zlatanova, Ivana; Taleb, Soraya; Bruneval, Patrick; Tedgui, Alain; Mallat, Ziad; Gibot, Sebastien; Ait-Oufella, Hafid

    2016-01-01

    BACKGROUND: Innate immune responses activated through myeloid cells contribute to the initiation, progression, and complications of atherosclerosis in experimental models. However, the critical upstream pathways that link innate immune activation to foam cell formation are still poorly identified.

  8. Contrasting effect of fish oil supplementation on the development of atherosclerosis in murine models

    DEFF Research Database (Denmark)

    Zampolli, Antonella; Bysted, Anette; Leth, Torben

    2006-01-01

    Objective: Increased fish oil intake is associated with protection against coronary heart disease and sudden death, while effects on atherosclerosis are controversial. We explored the effects of supplementing fish oil (rich in n-3 polyunsaturated fatty acids, PUFA) or corn oil (rich in n-6 PUFA......) in two different models of atherosclerosis. Methods and Results: Sixty-three low density lipoprotein receptor-deficient (LDLR-/-) mice and sixty-nine apolipoprotein E-deficient (apoE(-/-)) mice were fed diets without supplementations or supplemented with either 1% fish oil or 1% corn oil. In apo......E(-/-) mice, neither fish oil nor corn oil had any major impact on plasma lipids or atherosclerosis. In LDLR-/- mice, conversely, the fish oil and the corn oil group had lower levels of LDL-cholesterol and triglycerides and had lesser atherosclerosis in the aortic root and in the entire aorta (P

  9. A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

    OpenAIRE

    Lin, Juan; Li, Hanjie; Yang, Min; Ren, Junming; Huang, Zhe; Han, Felicia; Huang, Jian; Ma, Jianhui; Zhang, Duanwu; Zhang, Zhirong; Wu, Jianfeng; Huang, Deli; Qiao, Muzhen; Jin, Guanghui; Wu, Qiao

    2013-01-01

    Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP) 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation reveal...

  10. The Role of Vaspin in the Development of Metabolic and Glucose Tolerance Disorders and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Rumyana Dimova

    2015-01-01

    Full Text Available In recent years, most research efforts have been focused on studying insulin-sensitizing adipokines. One of the most recently discovered adipokines is vaspin, a visceral adipose tissue-derived serine protease inhibitor. Vaspin levels have been found significantly increased in mice with obesity and insulin resistance. It has been assumed that vaspin serves as an insulin sensitizer with anti-inflammatory effects and might act as a compensatory mechanism in response to decreased insulin sensitivity. Most studies in humans have shown a positive correlation between vaspin gene expression and serum levels, and metabolic syndrome parameters. Vaspin gene expression is influenced by age and gender, and the administration of insulin sensitizers enhances it in mice, whereas the use of metformin decreases serum vaspin levels in humans, probably due to different regulatory mechanisms. Presumably vaspin plays local and endocrine role in the development of initial and advanced atherosclerosis in obese subjects and might be used as a predictor of coronary and cerebrovascular disease. It is believed that vaspin could be regarded as a new link between obesity and related metabolic disorders, including glucose intolerance. The entire understanding of vaspin intimate mechanism of action might enable the development of novel etiology-based treatment strategies, targeting metabolic and glucose tolerance disorders.

  11. Inhibition of leukocyte-type 12-lipoxygenase by guava tea leaves prevents development of atherosclerosis.

    Science.gov (United States)

    Takahashi, Yoshitaka; Otsuki, Akemi; Mori, Yoshiko; Kawakami, Yuki; Ito, Hideyuki

    2015-11-01

    Oxidation of low-density lipoprotein (LDL) is one of the crucial steps for atherosclerosis development, and an essential role of leukocyte-type 12-lipoxygenase expressed in macrophages in this process has been demonstrated. The biochemical mechanism of the oxidation of circulating LDL by leukocyte-type 12-lipoxygenase in macrophages has been proposed. The major ingredients in guava tea leaves which inhibited the catalytic activity of leukocyte-type 12-lipoxygenase were quercetin and ethyl gallate. Administration of extracts from guava tea leaves to apoE-deficient mice significantly attenuated atherogenic lesions in the aorta and aortic sinus. We recently showed that Qing Shan Lu Shui inhibited the catalytic activity of leukocyte-type 12-lipoxygenase. The major components inhibiting the enzyme contained in Qing Shan Lu Shui were identified to be novel monoterpene glycosides. The anti-atherogenic effect of the tea leaves might be attributed to the inhibition of leukocyte-type 12-lipoxygenase by these components. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Efficacy of bioactive compounds from extra virgin olive oil to modulate atherosclerosis development.

    Science.gov (United States)

    Lou-Bonafonte, José M; Arnal, Carmen; Navarro, María A; Osada, Jesús

    2012-07-01

    As olive oil is the main source of calories in the Mediterranean diet, a great deal of research has been devoted to characterizing its role in atherosclerosis. Virgin olive oil is an oily matrix that contains hydrocarbons, mainly squalene; triterpenes such as uvaol, erythrodiol, oleanolic, and maslinic acid; phytosterols; and a wide range of phenolic compounds comprising simple phenols, flavonoids, secoiridoids, and lignans. In this review, we analyze the studies dealing with atherosclerosis and olive oil in several species. A protective role of virgin olive oil against atherosclerosis has been shown in ApoE-deficient mice and hamsters. In the former animal, sex, dose, and dietary cholesterol are modulators of the outcome. Contradictory findings have been reported for rabbits, a circumstance that could be due to the profusion of experimental designs, differing in terms of doses and animal strains, as well as sources of olive oils. This role has yet to be fully validated in humans. Minor components of olive oil have been shown to be involved in atherosclerosis protection. Nevertheless, evidence of the potential of isolated compounds or the right combination of them to achieve the antiatherosclerotic effect of virgin olive oil is inconclusive and will undoubtedly require further experimental support. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    International Nuclear Information System (INIS)

    Lin, Yan-Jie; Juan, Chi-Chang; Kwok, Ching-Fai; Hsu, Yung-Pei; Shih, Kuang-Chung; Chen, Chin-Chang; Ho, Low-Tone

    2015-01-01

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET A R during insulin resistance, ET A R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET A R expression, but not ET B R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET A R pathway suppressed insulin

  14. Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice.

    Science.gov (United States)

    Dorighello, Gabriel G; Rovani, Juliana C; Luhman, Christopher J F; Paim, Bruno A; Raposo, Helena F; Vercesi, Anibal E; Oliveira, Helena C F

    2014-03-28

    Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-α and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia.

  15. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yan-Jie [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Juan, Chi-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Kwok, Ching-Fai [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hsu, Yung-Pei [Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Shih, Kuang-Chung [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chen, Chin-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Ho, Low-Tone, E-mail: ltho@vghtpe.gov.tw [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China)

    2015-05-08

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance, ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway

  16. The effect of cigarette smoking on endothelial damage and atherosclerosis development – modeled and analyzed using Petri nets

    Directory of Open Access Journals (Sweden)

    Chmielewska Kaja

    2017-06-01

    Full Text Available Atherosclerosis as one of the crucial causes of cardiovascular diseases (CVD is the leading reason of death worldwide. One of the contributing factors to this phenomenon is endothelial dysfunction, which is associated with the impact of various agents and their interactions. Tobacco smoke is one of the well known factors here. For better understanding of its significance a model of its impact on atherosclerotic plaque formation has been proposed. The model contains selected aspects of the influence of tobacco smoke, dual function of nitric oxide (NO (influence of various mechanisms on NO bioavailability, oxidative stress which promotes low density lipoproteins oxidation, macrophages significance and other mechanisms leading to an aggravation of the endothelial disturbances. The model has been built using Petri nets theory and the analysis has been based on t-invariants. This approach allowed to confirm the important role of inflammation and oxidative stress in atherosclerosis development and moreover it has shown the considerable influence of the cigarette smoke.

  17. 56Fe accelerates development of atherosclerosis in apoE -/-mice

    Science.gov (United States)

    Kucik, Dennis; Yu, Tao; Parks, Brian; Yu, Shaohua; Srivastava, Roshni; Gupta, Kiran; Wu, Xing; Khaled, Saman; Chang, Polly; Kabarowski, Janusz

    Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. For example, for women with early breast cancer, the benefit of radiotherapy can be nearly offset by the increased risk of mortality from cardiovascular disease. Head and neck cancer patients who undergo radiation treatment are at significantly elevated risk of stroke, even in a relatively young patient population that would not normally be at risk for atheroscle-rosis. Similarly, atomic bomb survivors had an increased incidence of mortality from coronary artery disease and stroke. Even radiation technologists working before 1950 (when occupational exposure was higher) had increased mortality due to circulatory diseases. Although much is known about the cardiovascular consequences these exposures to X-raus and gamma radiation, the response to the type of radiation likely to be encountered in prolonged space flight has not been determined. A key component of this cosmic radiation is 56Fe, which is particularly damaging to tissues. Using collimated beams, we selectively irradiated aortic arches and carotids (only) of the well-established apoE -/-atherosclerosis mouse model to test directly whether 56Fe exposure is a cardiovascular risk factor. Mice were sacrificed at 13 weeks post-irradiation and dissected, and aortas were divided into areas that had been targeted by the ion beam and those that were not. The area that was covered by plaques was then quantified. Plaque area at 13 weeks post-irradiation was significantly greater in targeted areas of mice that had received 5 Gy of 56Fe as compared to age-and sex-matched un-irradiated controls. In the carotid arteries and aortic roots, significantly greater atherosclerosis was apparent for a 2Gy exposure as well (the lowest dose tested). This demonstrates that even a single exposure to heavy ion radiation is capable of triggering events that culminate in cardiovascular disease, even long after the exposure has

  18. L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.

    Science.gov (United States)

    Aji, W; Ravalli, S; Szabolcs, M; Jiang, X C; Sciacca, R R; Michler, R E; Cannon, P J

    1997-01-21

    The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental L-arginine and group 4 received L-arginine and N omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS). Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P < .01) in the cholesterol-fed mice given L-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues. The data indicate that L-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L-arginine are mediated by NOS. The data suggest that L-arginine may be beneficial in familial hypercholesterolemia.

  19. Effect of immunization against ox-LDL with two different antigens on formation and development of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Saberi Salb-Ali

    2007-11-01

    Full Text Available Abstract Background Several studies were pointed to oxidized LDL (ox-LDL as one of the main immunogenes which have important roles in primary lesions of atherosclerosis. In this study, by immunization against ox-LDL with two different antigens in an animal model (rabbit and consideration of its effect on two different dietary regimens; we tried to clear relation between immune system and atherosclerosis. Methods LDL was isolated from hypercholesterolemic rabbits plasma and oxidized with MDA or Cu++. Rabbits were divided to three groups and immunized with MDA-LDL or Cu-LDL or phosphate-buffer (PBS as a control group. Immunization was repeated after 2, 4, 6, and 8 weeks and concentration of antibodies against ox-LDL was measured in each stage. After immunization, rabbits in each group were divided to two subgroups based on the dietary regimen (fed normal or high cholesterol diet. At the beginning and the end of the study, biochemical factors were measured. Also, fatty streaks in aorta and left and right coronary arteries evaluated. Results Immunization with Cu2+-LDL and MDA-LDL induced statistically significant antibodies against ox-LDL. In hypercholesterolemic rabbits immunized with MDA-LDL the level of cholesterol, LDL-cholesterol, triglyceride, fasting blood sugar and fatty streak lesions in aorta and right coronary arteries were significantly decreased as compared with non-immunized high-cholesterol group. Immunization with Cu2+-LDL in hypercholesterolemic rabbits significantly decreased triglyceride, fasting blood sugar, cholesterol and CRP. No significant differences were detected in the fatty streak lesions in this group as compared with non-immunized high-cholesterol diet. In groups under normal diet immunized with MDA-LDL or Cu2+-LDL no significant effect on biochemical factors and atherosclerotic lesions were observed. Conclusion This study indicates that although the effect of produced antibodies in several methods and different dietary

  20. Aliskiren inhibits atherosclerosis development and improves plaque stability in APOE*3Leiden.CETP transgenic mice with or without treatment with atorvastatin

    NARCIS (Netherlands)

    Kühnast, S.; Hoorn, J.W.A. van der; Hoek, A.M. van den; Havekes, L.M.; Liau, G.; Jukema, J.W.; Princen, H.M.G.

    2012-01-01

    Objective: Aliskiren is the first commercially available, orally active, direct renin inhibitor approved to treat hypertension. The renin-angiotensin system has been shown to be a significant contributor to the development of hypercholesterolemia-induced atherosclerosis. The aim of this study was to

  1. Intracranial atherosclerosis: current concepts.

    Science.gov (United States)

    Arenillas, Juan F

    2011-01-01

    The most relevant ideas discussed in this article are described here. Intracranial atherosclerotic disease (ICAD) represents the most common cause of ischemic stroke worldwide. Its importance in whites may have been underestimated. New technical developments, such as high-resolution MRI, allow direct assessment of the intracranial atherosclerotic plaque, which may have a profound impact on ICAD diagnosis and therapy in the near future. Early detection of ICAD may allow therapeutic intervention while the disease is still asymptomatic. The Barcelonès Nord and Maresme Asymptomatic Intracranial Atherosclerosis Study is presented here. The main prognostic factors that characterize the patients who are at a higher risk for ICAD recurrence are classified and discussed. The best treatment for ICAD remains to be established. The Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Study is currently ongoing to address this crucial issue. These and other topics will be discussed at the Fifth International Intracranial Atherosclerosis Conference (Valladolid, Spain, autumn 2011).

  2. Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

    International Nuclear Information System (INIS)

    Aguilar, E.C.; Jascolka, T.L.; Teixeira, L.G.; Lages, P.C.; Ribeiro, A.C.C.; Vieira, E.L.M.; Peluzio, M.C.G.; Alvarez-Leite, J.I.

    2012-01-01

    Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr −/− , C57BL/6-background). Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12) or 7% pequi oil (Pequi group, N = 12) for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein) and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units). Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action

  3. Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar, E.C. [Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Jascolka, T.L. [Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Teixeira, L.G.; Lages, P.C.; Ribeiro, A.C.C.; Vieira, E.L.M. [Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Peluzio, M.C.G. [Departamento de Nutrição, Universidade Federal de Viçosa, Viçosa, MG (Brazil); Alvarez-Leite, J.I. [Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-05-11

    Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr{sup −/−}, C57BL/6-background). Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12) or 7% pequi oil (Pequi group, N = 12) for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein) and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units). Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action.

  4. Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

    Directory of Open Access Journals (Sweden)

    E.C. Aguilar

    2012-07-01

    Full Text Available Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr-/-, C57BL/6-background. Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12 or 7% pequi oil (Pequi group, N = 12 for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units. Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action.

  5. Inflammation and immune system interactions in atherosclerosis

    NARCIS (Netherlands)

    Legein, Bart; Temmerman, Lieve; Biessen, Erik A. L.; Lutgens, Esther

    2013-01-01

    Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 16.7 million deaths each year. The underlying cause of the majority of CVD is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall.

  6. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    Boshuizen, M.C.S.

    2016-01-01

    Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as

  7. Cytomegalovirus vaccines under clinical development

    OpenAIRE

    Schleiss, Mark R

    2016-01-01

    Abstract Congenital cytomegalovirus (CMV) infection is the most common infectious cause of disability in newborn infants. CMV also causes serious disease in solid organ (SOT) and haematopoietic stem cell transplant (HSCT) recipients. In otherwise healthy children and adults, primary CMV infection rarely causes illness. However, even asymptomatic CMV infections may predispose an individual towards an increased risk of atherosclerosis, cancer and immune senescence over the life course, although...

  8. Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM{sub 10})

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Ryohei; Hiraiwa, Kunihiko; Cheng, Jui Chih [UBC James Hogg Research Centre, St. Paul' s Hospital, University of British Columbia, Vancouver (Canada); Bai, Ni [UBC James Hogg Research Centre, St. Paul' s Hospital, University of British Columbia, Vancouver (Canada); Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver (Canada); Vincent, Renaud [Environmental Health Sciences and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa (Canada); Francis, Gordon A.; Sin, Don D. [UBC James Hogg Research Centre, St. Paul' s Hospital, University of British Columbia, Vancouver (Canada); Van Eeden, Stephan F., E-mail: Stephan.vanEeden@hli.ubc.ca [UBC James Hogg Research Centre, St. Paul' s Hospital, University of British Columbia, Vancouver (Canada)

    2013-10-01

    Exposure to ambient air particulate matter (particles less than 10 μm or PM{sub 10}) has been shown to be an independent risk factor for the development and progression of atherosclerosis. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have well-established anti-inflammatory properties. The aim of this study was to determine the impact of statins on the adverse functional and morphological changes in blood vessels induced by PM{sub 10}. New Zealand White rabbits fed with a high fat diet were subjected to balloon injury to their abdominal aorta followed by PM{sub 10}/saline exposure for 4 weeks ± lovastatin (5 mg/kg/day) treatment. PM{sub 10} exposure accelerated balloon catheter induced plaque formation and increased intimal macrophages and lipid accumulation while lovastatin attenuated these changes and promoted smooth muscle cell recruitment into plaques. PM{sub 10} impaired vascular acetylcholine (Ach) responses and increased vasoconstriction induced by phenylephrine as assessed by wire myograph. Supplementation of nitric oxide improved the impaired Ach responses. PM{sub 10} increased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in blood vessels and increased the plasma levels of endothelin-1 (ET-1). Incubation with specific inhibitors for iNOS, COX-2 or ET-1 in the myograph chambers significantly improved the impaired vascular function. Lovastatin decreased the expression of these mediators in atherosclerotic lesions and improved endothelial dysfunction. However, lovastatin was unable to reduce blood lipid levels to the baseline level in rabbits exposed to PM{sub 10}. Taken together, statins protect against PM{sub 10}-induced cardiovascular disease by reducing atherosclerosis and improving endothelial function via their anti-inflammatory properties. - Highlights: • Coarse particulate matter (PM{sub 10}) accelerated balloon injury-induced plaque formation. • Lovastatin decreased intimal

  9. Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM10)

    International Nuclear Information System (INIS)

    Miyata, Ryohei; Hiraiwa, Kunihiko; Cheng, Jui Chih; Bai, Ni; Vincent, Renaud; Francis, Gordon A.; Sin, Don D.; Van Eeden, Stephan F.

    2013-01-01

    Exposure to ambient air particulate matter (particles less than 10 μm or PM 10 ) has been shown to be an independent risk factor for the development and progression of atherosclerosis. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have well-established anti-inflammatory properties. The aim of this study was to determine the impact of statins on the adverse functional and morphological changes in blood vessels induced by PM 10 . New Zealand White rabbits fed with a high fat diet were subjected to balloon injury to their abdominal aorta followed by PM 10 /saline exposure for 4 weeks ± lovastatin (5 mg/kg/day) treatment. PM 10 exposure accelerated balloon catheter induced plaque formation and increased intimal macrophages and lipid accumulation while lovastatin attenuated these changes and promoted smooth muscle cell recruitment into plaques. PM 10 impaired vascular acetylcholine (Ach) responses and increased vasoconstriction induced by phenylephrine as assessed by wire myograph. Supplementation of nitric oxide improved the impaired Ach responses. PM 10 increased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in blood vessels and increased the plasma levels of endothelin-1 (ET-1). Incubation with specific inhibitors for iNOS, COX-2 or ET-1 in the myograph chambers significantly improved the impaired vascular function. Lovastatin decreased the expression of these mediators in atherosclerotic lesions and improved endothelial dysfunction. However, lovastatin was unable to reduce blood lipid levels to the baseline level in rabbits exposed to PM 10 . Taken together, statins protect against PM 10 -induced cardiovascular disease by reducing atherosclerosis and improving endothelial function via their anti-inflammatory properties. - Highlights: • Coarse particulate matter (PM 10 ) accelerated balloon injury-induced plaque formation. • Lovastatin decreased intimal macrophages, lipid accumulation, and

  10. Function and Therapeutic Potential of Mesenchymal Stem Cells in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Feifei Li

    2017-05-01

    Full Text Available Atherosclerosis is a complicated disorder and largely attributable to dyslipidaemia and chronic inflammation. Despite therapeutic advances over past decades, atherosclerosis remains the leading cause of mortality worldwide. Due to their capability of immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs have evolved as an attractive therapeutic agent in various diseases including atherosclerosis. Accumulating evidences support the protective role of MSCs in all stages of atherosclerosis. In this review, we highlight the current understanding of MSCs including their characteristics such as molecular markers, tissue distribution, migratory property, immune-modulatory competence, etc. We also summarize MSC functions in animal models of atherosclerosis. MSC transplantation is able to modulate cytokine and chemokine secretion, reduce endothelial dysfunction, promote regulatory T cell function, decrease dyslipidemia, and stabilize vulnerable plaques during atherosclerosis development. In addition, MSCs may migrate to lesions where they develop into functional cells during atherosclerosis formation. Finally, the perspectives of MSCs in clinical atherosclerosis therapy are discussed.

  11. Heart type fatty acid binding protein response and subsequent development of atherosclerosis in insulin resistant polycystic ovary syndrome patients.

    Science.gov (United States)

    Cakir, Evrim; Ozbek, Mustafa; Sahin, Mustafa; Cakal, Erman; Gungunes, Askin; Ginis, Zeynep; Demirci, Taner; Delibasi, Tuncay

    2012-12-18

    Women with polycystic ovary syndrome (PCOS) have higher risk for cardiovascular disease (CVD). Heart type fatty acid binding protein (HFABP) has been found to be predictive for myocardial ischemia.Wet ested whether HFABP is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease. This was a prospective, cross sectional controlled study conducted in a training and research hospital.The study population consisted of 46 reproductive-age PCOS women and 28 control subjects. We evaluated anthropometric and metabolic parameters, carotid intima media thickness and HFABP levels in both PCOS patients and control group. Mean fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol, free testosterone, total testosterone, carotid intima media thickness (CIMT) levels were significantly higher in PCOS patients. Although HFABP levels were higher in PCOS patients, the difference did not reach statistically significant in early age groups. After adjustment for age and body mass index, HFABP level was positive correlated with hsCRP, free testosterone levels, CIMT and HOMA-IR. Heart type free fatty acid binding protein appeared to have an important role in metabolic response and subsequent development of atherosclerosis in insulin resistant, hyperandrogenemic PCOS patients.

  12. Heart type fatty acid binding protein response and subsequent development of atherosclerosis in insulin resistant polycystic ovary syndrome patients

    Directory of Open Access Journals (Sweden)

    Cakir Evrim

    2012-12-01

    Full Text Available Abstract Background Women with polycystic ovary syndrome (PCOS have higher risk for cardiovascular disease (CVD. Heart type fatty acid binding protein (HFABP has been found to be predictive for myocardial ischemia.Wet ested whether HFABP is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease. Methods This was a prospective, cross sectional controlled study conducted in a training and research hospital.The study population consisted of 46 reproductive-age PCOS women and 28 control subjects. We evaluated anthropometric and metabolic parameters, carotid intima media thickness and HFABP levels in both PCOS patients and control group. Results Mean fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR, triglyceride, total cholesterol, low density lipoprotein cholesterol, free testosterone, total testosterone, carotid intima media thickness (CIMT levels were significantly higher in PCOS patients. Although HFABP levels were higher in PCOS patients, the difference did not reach statistically significant in early age groups. After adjustment for age and body mass index, HFABP level was positive correlated with hsCRP, free testosterone levels, CIMT and HOMA-IR. Conclusions Heart type free fatty acid binding protein appeared to have an important role in metabolic response and subsequent development of atherosclerosis in insulin resistant, hyperandrogenemic PCOS patients.

  13. [Potential protective role of nitric oxide and Hsp70 linked to functional foods in the atherosclerosis].

    Science.gov (United States)

    Camargo, Alejandra B; Manucha, Walter

    Atherosclerosis, one of the main pathologic entities considered epidemic and a worldwide public health problem, is currently under constant review as regards its basic determining mechanisms and therapeutic possibilities. In this regard, all patients afflicted with the disease exhibit mitochondrial dysfunction, oxidative stress and inflammation. Interestingly, nitric oxide - a known vasoactive messenger gas - has been closely related to the inflammatory, oxidative and mitochondrial dysfunctional process that characterizes atherosclerosis. In addition, it has recently been demonstrated that alterations in the bioavailability of nitric oxide would induce the expression of heat shock proteins. This agrees with the use of functional foods as a strategy to prevent both vascular aging and the development of atherosclerosis. Finally, a greater knowledge regarding the mechanisms implied in the development of atherosclerosis will enable proposing new and possible hygiene, health and therapeutic interventions. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis.

    Science.gov (United States)

    He, Hongliang; Yuan, Quan; Bie, Jinghua; Wallace, Ryan L; Yannie, Paul J; Wang, Jing; Lancina, Michael G; Zolotarskaya, Olga Yu; Korzun, William; Yang, Hu; Ghosh, Shobha

    2018-03-01

    Dysfunctional macrophages underlie the development of several diseases including atherosclerosis where accumulation of cholesteryl esters and persistent inflammation are 2 of the critical macrophage processes that regulate the progression as well as stability of atherosclerotic plaques. Ligand-dependent activation of liver-x-receptor (LXR) not only enhances mobilization of stored cholesteryl ester but also exerts anti-inflammatory effects mediated via trans-repression of proinflammatory transcription factor nuclear factor kappa B. However, increased hepatic lipogenesis by systemic administration of LXR ligands (LXR-L) has precluded their therapeutic use. The objective of the present study was to devise a strategy to selectively deliver LXR-L to atherosclerotic plaque-associated macrophages while limiting hepatic uptake. Mannose-functionalized dendrimeric nanoparticles (mDNP) were synthesized to facilitate active uptake via the mannose receptor expressed exclusively by macrophages using polyamidoamine dendrimer. Terminal amine groups were used to conjugate mannose and LXR-L T091317 via polyethylene glycol spacers. mDNP-LXR-L was effectively taken up by macrophages (and not by hepatocytes), increased expression of LXR target genes (ABCA1/ABCG1), and enhanced cholesterol efflux. When administered intravenously to LDLR-/- mice with established plaques, significant accumulation of fluorescently labeled mDNP-LXR-L was seen in atherosclerotic plaque-associated macrophages. Four weekly injections of mDNP-LXR-L led to significant reduction in atherosclerotic plaque progression, plaque necrosis, and plaque inflammation as assessed by expression of nuclear factor kappa B target gene matrix metalloproteinase 9; no increase in hepatic lipogenic genes or plasma lipids was observed. These studies validate the development of a macrophage-specific delivery platform for the delivery of anti-atherosclerotic agents directly to the plaque-associated macrophages to attenuate plaque

  15. Proliferating macrophages prevail in atherosclerosis.

    Science.gov (United States)

    Randolph, Gwendalyn J

    2013-09-01

    Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment of circulating monocytes.

  16. Mouse models for atherosclerosis and pharmaceutical modifiers

    NARCIS (Netherlands)

    Zadelaar, A.S.M.; Kleemann, R.; Verschuren, L.; Vries-van der Weij, J. de; Hoorn, J. van der; Princen, H.M.; Kooistra, T.

    2007-01-01

    Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically

  17. Recent advances in the development of PET/SPECT probes for atherosclerosis imaging

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Yoich; Kuge, Yuji [Hokkaido University, Sapporo (Japan)

    2016-12-15

    The rupture of vulnerable atherosclerotic plaques and subsequent thrombus formation are the major causes of myocardial and cerebral infarction. Accordingly, the detection of vulnerable plaques is important for risk stratification and to provide appropriate treatment. Inflammation imaging using 2-deoxy-2-[{sup 18}F]fluoro-D-glucose ({sup 18}F-FDG) has been most extensively studied for detecting vulnerable atherosclerotic plaques. It is of great importance to develop PET/SPECT probes capable of specifically visualizing the biological molecules involved in atherosclerotic plaque formation and/or progression. In this article, we review recent advances in the development of PET/SPECT probes for visualizing atherosclerotic plaques and their application to therapy monitoring, mainly focusing on experimental studies.

  18. Inflammasomes and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    S. Vallurupalli, MD

    2016-09-01

    Full Text Available Inflammation plays an important role in atherosclerosis. Inflammasomes play a crucial role in innate immunity, which mediates the body’s response to various pathogens. Of the different types of inflammasomes, NLRP3 has been implicated in atherosclerosis through the production of proinflammatory cytokines, IL-1β and IL-18. This review describes the role of the NLRP3 inflammasome in atherosclerosis and discusses potential therapeutic targets in the inflammasome pathway.

  19. Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Daniel A. Giles

    2016-11-01

    Full Text Available Objectives: Obesity and obesity-associated inflammation is central to a variety of end-organ sequelae including atherosclerosis, a leading cause of death worldwide. Although mouse models have provided important insights into the immunopathogenesis of various diseases, modeling atherosclerosis in mice has proven difficult. Specifically, wild-type (WT mice are resistant to developing atherosclerosis, while commonly used genetically modified mouse models of atherosclerosis are poor mimics of human disease. The lack of a physiologically relevant experimental model of atherosclerosis has hindered the understanding of mechanisms regulating disease development and progression as well as the development of translational therapies. Recent evidence suggests that housing mice within their thermoneutral zone profoundly alters murine physiology, including both metabolic and immune processes. We hypothesized that thermoneutral housing would allow for augmentation of atherosclerosis induction and progression in mice. Methods: ApoE−/− and WT mice were housed at either standard (TS or thermoneutral (TN temperatures and fed either a chow or obesogenic “Western” diet. Analysis included quantification of (i obesity and obesity-associated downstream sequelae, (ii the development and progression of atherosclerosis, and (iii inflammatory gene expression pathways related to atherosclerosis. Results: Housing mice at TN, in combination with an obesogenic “Western” diet, profoundly augmented obesity development, exacerbated atherosclerosis in ApoE−/− mice, and initiated atherosclerosis development in WT mice. This increased disease burden was associated with altered lipid profiles, including cholesterol levels and fractions, and increased aortic plaque size. In addition to the mild induction of atherosclerosis, we similarly observed increased levels of aortic and white adipose tissue inflammation and increased circulating immune cell expression of pathways

  20. A comparison of ultrasound measurements to assess carotid atherosclerosis development in subjects with and without type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Zinman Bernard

    2005-06-01

    Full Text Available Abstract Background Subjects with type 2 diabetes are at an increased risk of vascular complications. The use of carotid ultrasound remains an attractive, non-invasive method to monitor atherosclerotic disease progression and/or response to treatment in patients with type 2 diabetes, with intima-media thickness routinely used as the gold standard to detect pathology. However, alternative measurements, such as plaque area or volume, may represent a potentially more powerful approach. Thus, the objective of this study was to compare the traditional intima-media thickness measurement against the novel total plaque volume measurement in analyzing carotid atherosclerosis development in individuals with type 2 diabetes. Methods The case-control study included 49 Oji-Cree adults with diabetes or impaired glucose tolerance, aged 21–69, and 49 sex- and age-matched normoglycemic subjects. At baseline, metabolic variables were measured, including body mass index, waist circumference, total cholesterol:high density lipoprotein ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid ultrasound measurements, 7 years later, assessed carotid arterial intima-media thickness and total plaque volume. Results At baseline, the two groups were well matched for smoking habits, hypertension, body mass index, and waist circumference. Differences were noted in baseline measurements of total cholesterol:high density lipoprotein (P = 0.0006, plasma triglycerides (P P P = 0.037, but not intima-media thickness measurements, were higher in subjects with diabetes/impaired glucose tolerance compared to the normoglycemic controls. Correlation between intima-media thickness and total plaque volume was moderate. Based on our study findings, to achieve power levels >0.70 when comparing intima-media thickness measurements for diabetics versus non-diabetics, thousands of study subjects are required. For comparing total plaque volume measurements, only hundreds of

  1. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Murilo Foppa

    2001-02-01

    Full Text Available Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

  2. Phytosterols and atherosclerosis

    DEFF Research Database (Denmark)

    Schrøder, Malene

    for decades for their natural ability to reduce cholesterol levels in the blood. In the last decade numerous food products added phytosterol esters have been placed on the market, e.g. yellow fat spread, yoghurt, dressing. The products are being marketed as a natural means for people who want to lower...... or advanced lesion) and quantitatively by stereological methods applied to evaluate the area of the intima and the ratio of intima:media on cross sections from three defined places on the aorta. The biochemical endpoint was the cholesterol content in the inner layer of the entire aorta, which is considered...... than 3% brassicasterol are not accepted on the European market. The aim of the study was to investigate the effect of dietary supplementation of RSO derived sterol, with high content of brassicasterols, and stanol esters on the development of atherosclerosis in cholesterol-fed heterozygous WHHL rabbits...

  3. Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Jinfan Tian

    2017-01-01

    Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

  4. Coronary atherosclerosis in medico-legal autopsy cases

    Directory of Open Access Journals (Sweden)

    VN Prasad

    2014-09-01

    Full Text Available Background: Coronary atherosclerosis is the major cause of death worldwide. Lifestyle and habits are the major contributory factor in the development of coronary atherosclerosis. Materials and Methods: This is an autopsy-based study in which 45 autopsy cases were randomly selected for study. Proximal one third of all three epicardial coronary arteries (LAD, LCX and RCA were dissected out for study and serial sections were made and stained with H&E method and under the light microscope. Atherosclerosis was graded according to American heart association classification. The risk factors (cigarette smoking, hypertension, diabetes, alcohol consumption, age, sex were also correlated with the grade of atherosclerosis. Results: Seventy-Eight percent of American Heart Association classification grade V lesions were seen in > 70 yrs of age. Almost all cases of > 70 yrs of age had American Heart Association classification grade > IV lesions. Out of all grade IV lesions, 88.9% was seen in male while only 11.1% in female. Similarly out of all grade V lesions, 77.8% was seen in male while 22.2% in female. LAD showed maximum involvement by higher grade lesion, followed by LCX and RCA. American Heart Association classification grade > IV in LAD, LCX and RCA was seen in 25(55.6%, 5(11.1%, and 3(6.7% cases respectively. Conclusion: Higher grade lesion occurs in advancing age. Various cardiovascular risk factors were significantly associated with higher grade of lesions. The multiple risk factors had a synergistic effect on the progression of coronary atherosclerosis. DOI: http://dx.doi.org/10.3126/jpn.v4i8.11492 Journal of Pathology of Nepal; Vol.4,No8(2014 607-611

  5. eNOS Glu298Asp polymorphism is associated with development of complicated plaques in patients from Serbia with advanced carotid atherosclerosis

    Directory of Open Access Journals (Sweden)

    Đurić Tamara

    2013-01-01

    Full Text Available Nitric oxide inhibits adhesion of thrombocytes, proliferation and migration of smooth muscle cells and restricts oxidation of atherogenic low-density lipoproteins. Therefore, decreased production or activity of NO may play a role in the initiation, progression or complications of atherosclerosis. The aim of this study was to estimate the effect of Glu298Asp eNOS gene polymorphism on the individual risk for development of complicated carotid atherosclerotic plaque in patients from Serbia with advanced carotid atherosclerosis (CA who had undergone endarterectomy. The study population included 233 patients. eNOS G894T gene polymorphism was identified by PCR and RFLP methods. Multivariate logistic regression analysis showed that Asp298Asp is an independent risk factor for the presence of complicated plaques in CA patients. Patients who were homozygous for the Asp298 allele had an adjusted OR of 4.36 for the development of complicated plaques compared to those that carry the Glu298 allele. Further validation and replication studies are needed. [Projekat Ministarstva nauke Republike Srbije, br. OI175085

  6. The Biochemistry of atherosclerosis

    National Research Council Canada - National Science Library

    Scanu, Angelo M; Getz, Godfrey S; Wissler, Robert W

    1979-01-01

    In this first full-length review of the biochemical parameters and their part in the pathogenesis of atherosclerosis, the reader will discover a range of coverage concerning basic etiological factors...

  7. Atherosclerosis in Juvenile Idiopathic Arthritis

    Directory of Open Access Journals (Sweden)

    Ewa Jednacz

    2012-01-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease of the arteries. Clinical consequences of the atherosclerotic process occur in the adult population, however atherosclerotic process begins in childhood. The classic risk factors for atherosclerosis include obesity, dyslipidaemia, age, gender or family history. In recent years, attention has been drawn to the similarity between atherosclerotic inflammatory processes and inflammatory changes in the course of systemic connective tissue disease, in particular systemic lupus etythematosus (SLE or rheumatoid arthritis (RA. There is also observed the similarity of the pathogenetic background of development of atherosclerosis and juvenile idiopathic arthritis (JIA. Elevated levels of pro-inflammatory cytokines are observed in the course of juvenile idiopathic arthritis. Also homocysteine concentrations, which may play a significant role in the development of atherosclerotic lesions, are observed higher in patients with JIA. Some studies revealed higher carotid intima-media thickness (IMT index values in children with JIA. In view of the fact that atherosclerotic process begins as early as in childhood, the introduction of appropriate preventive measures in children is a matter of utmost importance.

  8. Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

    Science.gov (United States)

    Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

    2010-01-01

    Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

  9. Oral microbiota in patients with atherosclerosis.

    Science.gov (United States)

    Fåk, Frida; Tremaroli, Valentina; Bergström, Göran; Bäckhed, Fredrik

    2015-12-01

    Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. To elucidate whether the oral microbiota composition differed between patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. The overall microbial structure was similar in controls and atherosclerosis patients, but patients with symptomatic atherosclerosis had higher relative abundance of Anaeroglobus (mean 0.040% (SD 0.049)) than the control group (0.010% (SD 0.028)) (P = 0.03). Using linear regression analysis, we found that Parvimonas associated positively with uCRP and Capnocytophaga, Catonella and Lactobacillus associated with blood lipid markers. In conclusion, abundance of Anaeroglobus in the oral cavity could be associated with symptomatic atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Air pollution is associated with the development of atherosclerosis via the cooperation of CD36 and NLRP3 inflammasome in ApoE-/- mice.

    Science.gov (United States)

    Du, Xihao; Jiang, Shuo; Zeng, Xuejiao; Zhang, Jia; Pan, Kun; Zhou, Ji; Xie, Yuquan; Kan, Haidong; Song, Weimin; Sun, Qinghua; Zhao, Jinzhuo

    2018-06-15

    Previous studies have indicated that the main air pollutant fine particulate matter (≤2.5 μm; PM 2.5 ) exposure is associated with the development of atherosclerosis. Although the mechanism is not fully illustrated, the inflammatory responses play an important role. The present study aimed to explore whether PM 2.5 -exacerbated atherosclerosis was mediated by the cooperation of cluster of differentiation 36 (CD36) and nucleotide-binding oligomerization domain-like receptor protein (NLRP3) inflammasome in apolipoprotein E -/- (ApoE -/- ) mice. Thirty-two ApoE -/- mice were randomly divided into two groups. One group was fed with high fat chow (HFC) for 10 weeks to establish atherosclerotic model, and the other was fed with normal chow (NC). From week 11, the mice were exposed to concentrated PM 2.5 (PM) or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. In both NC and HFC groups, PM 2.5 exposure induced the formation of atherosclerosis plaque. Similarly, PM mice appeared higher lipid content in the aortic root than that in the FA mice. Compared with the FA mice, PM mice appeared a decrease in high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 along with an increase in apolipoprotein B, low density lipoprotein-cholesterol (LDL-C) and oxidized low-density lipoprotein (ox-LDL). Moreover, PM 2.5 exposure induced increase of CD36 in serum and aorta. In both NC and HFC groups, NLRP3 inflammasome activation-related indicators were activated or increased in the aorta of the PM mice when compared with the FA mice. The cooperation of CD36 and NLRP3 inflammasome activation may be the potential mechanisms linkixposed to concentrated PM 2.5 (PM) or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. In both NC and HFC groups, PM 2.5 exposure induced the formation of atherosclerosis plaque. Similarly, PM mice appeared higher lipid content in the aortic

  11. Heat Shock Proteins: Pathogenic Role in Atherosclerosis and Potential Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Arman Kilic

    2012-01-01

    Full Text Available Heat shock proteins (HSPs are a highly conserved group of proteins that are constitutively expressed and function as molecular chaperones, aiding in protein folding and preventing the accumulation of misfolded proteins. In the arterial wall, HSPs have a protective role under normal physiologic conditions. In disease states, however, HSPs expressed on the vascular endothelial cell surface can act as targets for detrimental autoimmunity due to their highly conserved sequences. Developing therapeutic strategies for atherosclerosis based on HSPs is challenged by the need to balance such physiologic and pathologic roles of these proteins. This paper summarizes the role of HSPs in normal vascular wall processes as well as in the development and progression of atherosclerosis. The potential implications of HSPs in clinical therapies for atherosclerosis are also discussed.

  12. Atherosclerosis: the interplay between lipids and immune cells

    NARCIS (Netherlands)

    Schaftenaar, Frank; Frodermann, Vanessa; Kuiper, Johan; Lutgens, Esther

    2016-01-01

    Cardiovascular disease is the leading cause of mortality worldwide. The underlying cause of the majority of cardiovascular disease is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall. However, today's picture of the

  13. (-)-anipamil retards atherosclerosis in Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Hansen, B F; Mortensen, A; Hansen, J F

    1995-01-01

    Calcium antagonists have been reported to limit atherosclerosis in cholesterol fed rabbits. The purpose of this study was to examine the effect of the calcium antagonist (-)-anipamil on the spontaneous development of atherosclerosis in homozygote WHHL rabbits. From the age of 7 weeks, three groups...... differences were found in serum lipids (i.e., VLDL, IDL, LDL, HDL) in the study period among the three groups. Plasma anipamil at the end of the study was 0.23 +/- 6, and 202 +/- 19 ng/ml, respectively, in the three treatment groups. The degree of atherosclerosis in the abdominal aorta was significantly lower...... (p atherosclerosis in the abdominal aorta in WHHL rabbits....

  14. Targeting the adaptive immune system: new strategies in the treatment of atherosclerosis

    NARCIS (Netherlands)

    Zarzycka, Barbara; Nicolaes, Gerry A. F.; Lutgens, Esther

    2015-01-01

    Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. Current treatment of atherosclerosis is focused on limiting its risk factors, such as hyperlipidemia or hypertension. However, treatments that target the inflammatory nature of atherosclerosis are still under

  15. Endothelial activation, endothelial dysfunction and premature atherosclerosis in systemic autoimmune diseases

    NARCIS (Netherlands)

    Bijl, M

    Atherosclerosis may be considered an inflammatory disease characterised by the development of atherosclerotic plaques and ischaemic cardiovascular events. Increased prevalence of cardiovascular morbidity and mortality due to (premature) atherosclerosis has been observed in patients with autoimmune

  16. Asymmetrical distribution of atherosclerosis in the carotid artery: identical patterns across age, race, and gender

    NARCIS (Netherlands)

    Tajik, Parvin; Meijer, Rudy; Duivenvoorden, Raphaël; Peters, Sanne A. E.; Kastelein, John J.; Visseren, Frank J.; Crouse, John R.; Palmer, Mike K.; Raichlen, Joel S.; Grobbee, Diederick E.; Bots, Michiel L.

    2012-01-01

    Background: Small autopsy studies and clinical practice indicated that carotid atherosclerosis develops in an asymmetrical helical pattern coinciding with regions of low shear stress. We investigated the distribution of carotid atherosclerosis as determined by maximum carotid intima-media thickness

  17. Nuclear medicine and atherosclerosis

    International Nuclear Information System (INIS)

    Sinzinger, H.; Virgolini, I.

    1990-01-01

    Although the pathomechanisms of atherosclerosis are well known, their radioisotopic monitoring is still in its early childhood. The current radioisotope techniques are of only limited value for contributing to the clinical diagnosis of atherosclerosis. The limited reaction time of cellular blood constituents (platelets, monocytes) with the vascular surface at the injury site makes it very difficult to catch the point of injury. Lipoproteins excellently allow receptor imaging, while vascular monitoring is only of scientific interest at present. Labelling and subsequent imaging of components of the coagulation cascade have not succeeded so far, nor have attempts using unspecific labels such as porphyrin, polyclonal IgG and Fc fragments, for example. Preliminary evidence indicates that radioisotopic techniques may be of great benefit in the future in elucidating functional aspects of the disease, while they do not contribute to examining the stage and extent of atherosclerosis. (orig.)

  18. Chronic Intermittent Hypoxia Induces Atherosclerosis

    OpenAIRE

    Savransky, Vladimir; Nanayakkara, Ashika; Li, Jianguo; Bevans, Shannon; Smith, Philip L.; Rodriguez, Annabelle; Polotsky, Vsevolod Y.

    2007-01-01

    Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.

  19. Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

    Science.gov (United States)

    Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

    2018-02-01

    The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

  20. Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite-Potential mechanism in the development of atherosclerosis

    International Nuclear Information System (INIS)

    Pereira, Flavia E.; Coffin, J. Douglas; Beall, Howard D.

    2007-01-01

    Arsenic exposure has been shown to exacerbate atherosclerosis, beginning with activation of the endothelium that lines the vessel wall. Endothelial barrier integrity is maintained by proteins of the adherens junction (AJ) such as vascular endothelial cadherin (VE-cadherin) and β-catenin and their association with the actin cytoskeleton. In the present study, human aortic endothelial cells (HAECs) were exposed to 1, 5 and 10 μM sodium arsenite [As(III)] for 1, 6, 12 and 24 h, and the effects on endothelial barrier integrity were determined. Immunofluorescence studies revealed formation of actin stress fibers and non-uniform VE-cadherin and β-catenin staining at cell-cell junctions that were concentration- and time-dependent. Intercellular gaps were observed with a measured increase in endothelial permeability. In addition, concentration-dependent increases in tyrosine phosphorylation (PY) of β-catenin and activation of protein kinase Cα (PKCα) were observed. Inhibition of PKCα restored VE-cadherin and β-catenin staining at cell-cell junctions and abolished the As(III)-induced formation of actin stress fibers and intercellular gaps. Endothelial permeability and PY of β-catenin were also reduced to basal levels. These results demonstrate that As(III) induces activation of PKCα, which leads to increased PY of β-catenin downstream of PKCα activation. Phosphorylation of β-catenin plausibly severs the association of VE-cadherin and β-catenin, which along with formation of actin stress fibers, results in intercellular gap formation and increased endothelial permeability. To the best of our knowledge, this is the first report demonstrating that As(III) causes a loss of endothelial monolayer integrity, which potentially could contribute to the development of atherosclerosis

  1. Development of an inflammation imaging tracer, 111In-DOTA-DAPTA, targeting chemokine receptor CCR5 and preliminary evaluation in an ApoE-/- atherosclerosis mouse model.

    Science.gov (United States)

    Wei, Lihui; Petryk, Julia; Gaudet, Chantal; Kamkar, Maryam; Gan, Wei; Duan, Yin; Ruddy, Terrence D

    2018-02-07

    Chemokine receptor 5 (CCR5) plays an important role in atherosclerosis. Our objective was to develop a SPECT tracer targeting CCR5 for imaging plaque inflammation by radiolabeling D-Ala-peptide T-amide (DAPTA), a CCR5 antagonist, with 111 In. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated DAPTA (DOTA-DAPTA) was labeled with 111 In. Cell uptake studies were conducted in U87-CD4-CCR5 and U87-MG cells. Biodistribution was determined in C57BL/6 mice. Autoradiography, en face and Oil Red O (ORO) imaging studies were performed in ApoE -/- mice. DOTA-DAPTA was radiolabeled with 111 In with high radiochemical purity (> 98%) and specific activity (70 MBq·nmol). 111 In-DOTA-DAPTA exhibited fast blood and renal clearance and high spleen uptake. The U87-CD4-CCR5 cells had significantly higher uptake in comparison to the U87-MG cells. The cell uptake was reduced by three times with DAPTA, indicating the receptor specificity of the uptake. Autoradiographic images showed significantly higher lesion uptake of 111 In-DOTA-DAPTA in ApoE -/- mice than that in C57BL/6 mice. The tracer uptake in 4 month old ApoE -/- high fat diet (HFD) mice with blocking agent was twofold lower than the same mice without the blocking agent, demonstrating the specificity of the tracer for the CCR5 receptor. 111 In-DOTA-DAPTA, specifically targeting chemokine receptor CCR5, is a potential SPECT agent for imaging inflammation in atherosclerosis.

  2. Cyanotic congenital heart disease and atherosclerosis.

    Science.gov (United States)

    Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas; Holstein-Rathlou, Niels-Henrik; Søndergaard, Lars

    2017-06-01

    Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Diet and Atherosclerosis | Grande | South African Medical Journal

    African Journals Online (AJOL)

    Among the various factors affecting the development of atherosclerosis and its complications, the diet emerges as an important influence. This article reviews the evidence linking diet and atherosclerosis; the relation between serum cholesterol concentration and incidence of coronary heart disease, and the effect of various ...

  4. What Is Atherosclerosis?

    Science.gov (United States)

    ... builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys. Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body. Overview The cause of atherosclerosis ...

  5. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    DA LUZ PROTASIO L.

    2001-01-01

    Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

  6. Osteoprotegerin as a marker of atherosclerosis

    DEFF Research Database (Denmark)

    Hosbond, Susanne Elisabeth; Poulsen, Tina Svenstrup; Diederichsen, Axel Cosmus Pyndt

    2012-01-01

    Abstract Objective: Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD) and cerebrovascular disease (CBVD) a syste......Abstract Objective: Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD) and cerebrovascular disease (CBVD...... with clearly defined cohorts qualified for this review. Results: In 11 studies OPG concentrations were elevated. Severity of atherosclerosis was significantly associated with higher OPG concentrations compared to healthy controls. No association between PAD and OPG concentrations was observed. Conclusion: OPG...

  7. Role of gut microbiota in atherosclerosis

    DEFF Research Database (Denmark)

    Jonsson, Annika Lindskog; Bäckhed, Gert Fredrik

    2017-01-01

    describe three pathways by which microbiota might affect atherogenesis. First, local or distant infections might cause a harmful inflammatory response that aggravates plaque development or triggers plaque rupture. Second, metabolism of cholesterol and lipids by gut microbiota can affect the development...... of atherosclerotic plaques. Third, diet and specific components that are metabolized by gut microbiota can have various effects on atherosclerosis; for example, dietary fibre is beneficial, whereas the bacterial metabolite trimethylamine-N-oxide is considered harmful. Although specific bacterial taxa have been...... associated with atherosclerosis, which is supported by increasing mechanistic evidence, several questions remain to be answered to understand fully how the microbiota contributes to atherosclerosis and cardiovascular disease. Such knowledge might pave the way for novel diagnostics and therapeutics based...

  8. Influence of Erythrocyte Membrane Stability in Atherosclerosis.

    Science.gov (United States)

    da Silva Garrote-Filho, Mario; Bernardino-Neto, Morun; Penha-Silva, Nilson

    2017-04-01

    The purpose of this study is to show how an excess of cholesterol in the erythrocyte membrane contributes stochastically to the progression of atherosclerosis, leading to damage in blood rheology and O 2 transport, deposition of cholesterol (from trapped erythrocytes) in an area of intraplaque hemorrhage, and local exacerbation of oxidative stress. Cholesterol contained in the membrane of erythrocytes trapped in an intraplaque hemorrhage contributes to the growth of the necrotic nucleus. There is even a relationship between the amount of cholesterol in the erythrocyte membrane and the severity of atherosclerosis. In addition, the volume variability among erythrocytes, measured by RDW, is predictive of a worsening of this disease. Erythrocytes contribute to the development of atherosclerosis in several ways, especially when trapped in intraplate hemorrhage. These erythrocytes are oxidized and phagocytosed by macrophages. The cholesterol present in the membrane of these erythrocytes subsequently contributes to the growth of the atheroma plaque. In addition, when they rupture, erythrocytes release hemoglobin, which leads to the generation of free radicals. Finally, increased RDW may predict the worsening of atherosclerosis, due to the effects of inflammation and oxidative stress on erythropoiesis and erythrocyte volume. A better understanding of erythrocyte participation in atherosclerosis may contribute to the improvement of the prevention and treatment strategies of this disease.

  9. ApoB and apoM - New aspects of lipoprotein biology in uremia-induced atherosclerosis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Bartels, Emil D.; Pedersen, Annemarie Aarup

    2017-01-01

    Chronic kidney disease affects as much as 13% of the population, and is associated with a markedly increased risk of developing cardiovascular disease. One of the underlying reasons is accelerated development of atherosclerosis. This can be ascribed both to increased occurrence of traditional...

  10. Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

    DEFF Research Database (Denmark)

    Bang, Christian A; Bro, Susanne; Bartels, Emil D

    2007-01-01

    Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild...... in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition....

  11. ATHEROSCLEROSIS DISEASE: A MULTI-FACTORIAL PATHOLOGY

    Directory of Open Access Journals (Sweden)

    Marcieli da Luz Giroldo1; Arienne Serrano Alves1; Francielle Baptista1

    2007-06-01

    Full Text Available Atherosclerosis or arterial stiffening is a gradual disease that restricts the normal blood flow in different areas of body and maylead to secondary illnesses as myocardial infarction and cerebral stroke. Innumerable factors are related to the development ofatherosclerosis, among them are the dyslipidemia; genetic factors; arterial hypertension; diabetes mellitus; obesity; smoking;lack of exercise; pulmonary infection by Chlamydia and stress. Due to multi-factorial atherosclerosis characteristics,innumerable drugs, with differentiated mechanisms of action, are being elaborated to be used in prevention and control of thisdisease. However, beyond the pharmacological therapy, a balanced diet, physical activity and elimination of risk habits, assmoking, also are need for controlling atherosclerosis progression, as well as for the increase of expectative and quality of life

  12. Oral microbiota in patients with atherosclerosis

    DEFF Research Database (Denmark)

    Fåk, Frida; Tremaroli, Valentina; Bergström, Göran

    2015-01-01

    BACKGROUND AND AIMS: Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested...... to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. METHODS: To elucidate whether the oral microbiota composition differed between...... patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. RESULTS...

  13. [Estimation of relation between homocysteine concentration and selected lipid parameters and adhesion molecules concentration in children with atherosclerosis risk factors].

    Science.gov (United States)

    Sierakowska-Fijałek, Anna; Baj, Zbigniew; Kaczmarek, Piotr; Stepień, Mariusz; Rysz, Jacek

    2008-10-01

    Atherosclerosis begins in childhood. At present among numerous risk factors of atherosclerosis the role of hiperhomocysteinemia in development of cardiovascular heart disease is taken under consideration. Atherogenic effect of homocystein is related to its cytotoxin action, conducting to endothelial dysfunction and damage. It is correlated with increase of the lipid levels in the blood serum and change of expression of the soluble forms of adhesion molecules. The aim of this study was to estimate relations between the homocystein serum concentration, expression of the selected adhesion molecules and the lipid levels in the blood serum in children with atherosclerosis risk factors. The group consisted of 670 children, 76 of them had atherosclerosis risk factors. In further examination 48 children have taken a part, whose parents were agreed for theirs participation in the program. The comparative group composed of 25 children without the risk factors. We determined total cholesterol (TC), triglycerides (TG), LDL cholesterol fraction (LDL-C), HDL cholesterol fraction (HDL-C), serum homocysteine concentration (Hcy), the expression of the soluble forms of adhesion molecules (sCAM): sP-selectin and sVCAM-1 (vascular cell adhesion molecule-1). Obesity, hypertension and lipid disorders in the shape of higher concentration of TC, LDL-C, TG and lower HDL-C were the most frequent risk factors in the investigated children. No significant differences in serum homocysteine concentration were observed between the investigated groups. However, its concentration was significantly higher in children with two atherosclerosis risk factors. No significant differences in expression of s-VCAM-1 were observed in the investigated groups, concentration of sP-selectin was significantly higher in children with atherosclerosis risk factors (phomocysteine and chosen adhesion molecules in children with atherosclerosis risk factors might potentially constitute the marker of early

  14. Endothelial GPR124 Exaggerates the Pathogenesis of Atherosclerosis by Activating Inflammation

    Directory of Open Access Journals (Sweden)

    Dong-Mei Gong

    2018-01-01

    Full Text Available Background/Aims: Endothelial cell dysfunction is the principal pathological process underlying atherosclerotic cardiovascular disease. G protein-coupled receptor 124 (GPR124, an orphan receptor in the adhesion GPCR subfamily, promotes angiogenesis in the brain. In the present study, we explored the role of endothelial GPR124 in the development and progression of atherosclerosis in adult mice. Methods: Using tetracycline-inducible transgenic systems, we generated mice expressing GPR124 specifically under control of the Tie-2 promoter. The animal model of atherosclerosis was constructed by intravenously injecting AAV-PCSK9DY into tetracycline-regulated mice and feeding the mice a high-fat diet for 16 consecutive weeks. Biochemical analysis and immunohistochemistry methods were used to address the role and mechanism of GPR124 in the pathological process of atherosclerosis. Results: Higher TC (total cholesterol and LDL-C (low density lipoprotein cholesterol levels in serum and greater lipid deposition in the aortic sinus were found in atherosclerotic mice with GPR124 overexpression, coincident with the elevated proliferation of smooth muscle cells. We observed an elevation of ONOO- in the aortic sinus in this model by using immunofluorescence, and the experiments showed that the specific overexpression of GPR124 in the endothelium induced the up-regulation of CD68, NLRP3 and caspase-1 levels in the aortic sinus. Conclusion: The above results indicate that manipulating GPR124 in the endothelium may contribute to delayed pathological progression of atherosclerosis.

  15. The Upregulation of Integrin αDβ2 (CD11d/CD18) on Inflammatory Macrophages Promotes Macrophage Retention in Vascular Lesions and Development of Atherosclerosis.

    Science.gov (United States)

    Aziz, Moammir H; Cui, Kui; Das, Mitali; Brown, Kathleen E; Ardell, Christopher L; Febbraio, Maria; Pluskota, Elzbieta; Han, Juying; Wu, Huaizhu; Ballantyne, Christie M; Smith, Jonathan D; Cathcart, Martha K; Yakubenko, Valentin P

    2017-06-15

    Macrophage accumulation is a critical step during development of chronic inflammation, initiating progression of many devastating diseases. Leukocyte-specific integrin α D β 2 (CD11d/CD18) is dramatically upregulated on macrophages at inflammatory sites. Previously we found that CD11d overexpression on cell surfaces inhibits in vitro cell migration due to excessive adhesion. In this study, we have investigated how inflammation-mediated CD11d upregulation contributes to macrophage retention at inflammatory sites during atherogenesis. Atherosclerosis was evaluated in CD11d -/- /ApoE -/- mice after 16 wk on a Western diet. CD11d deficiency led to a marked reduction in lipid deposition in aortas and isolated macrophages. Macrophage numbers in aortic sinuses of CD11d -/- mice were reduced without affecting their apoptosis and proliferation. Adoptive transfer of fluorescently labeled wild-type and CD11d -/- monocytes into ApoE -/- mice demonstrated similar recruitment from circulation, but reduced accumulation of CD11d -/- macrophages within the aortas. Furthermore, CD11d expression was significantly upregulated on macrophages in atherosclerotic lesions and M1 macrophages in vitro. Interestingly, expression of the related ligand-sharing integrin CD11b was not altered. This difference defines their distinct roles in the regulation of macrophage migration. CD11d-deficient M1 macrophages demonstrated improved migration in a three-dimensional fibrin matrix and during resolution of peritoneal inflammation, whereas migration of CD11b -/- M1 macrophages was not affected. These results prove the contribution of high densities of CD11d to macrophage arrest during atherogenesis. Because high expression of CD11d was detected in several inflammation-dependent diseases, we suggest that CD11d/CD18 upregulation on proinflammatory macrophages may represent a common mechanism for macrophage retention at inflammatory sites, thereby promoting chronic inflammation and disease development

  16. Raman spectroscopy imaging reveals interplay between atherosclerosis and medial calcification in the human aorta

    Science.gov (United States)

    You, Amanda Y. F.; Bergholt, Mads S.; St-Pierre, Jean-Philippe; Kit-Anan, Worrapong; Pence, Isaac J.; Chester, Adrian H.; Yacoub, Magdi H.; Bertazzo, Sergio; Stevens, Molly M.

    2017-01-01

    Medial calcification in the human aorta accumulates during aging and is known to be aggravated in several diseases. Atherosclerosis, another major cause of cardiovascular calcification, shares some common aggravators. However, the mechanisms of cardiovascular calcification remain poorly understood. To elucidate the relationship between medial aortic calcification and atherosclerosis, we characterized the cross-sectional distributions of the predominant minerals in aortic tissue, apatite and whitlockite, and the associated extracellular matrix. We also compared the cellular changes between atherosclerotic and nonatherosclerotic human aortic tissues. This was achieved through the development of Raman spectroscopy imaging methods that adapted algorithms to distinguish between the major biomolecules present within these tissues. We present a relationship between apatite, cholesterol, and triglyceride in atherosclerosis, with the relative amount of all molecules concurrently increased in the atherosclerotic plaque. Further, the increase in apatite was disproportionately large in relation to whitlockite in the aortic media directly underlying a plaque, indicating that apatite is more pathologically significant in atherosclerosis-aggravated medial calcification. We also discovered a reduction of β-carotene in the whole aortic intima, including a plaque in atherosclerotic aortic tissues compared to nonatherosclerotic tissues. This unprecedented biomolecular characterization of the aortic tissue furthers our understanding of pathological and physiological cardiovascular calcification events in humans. PMID:29226241

  17. NMR imaging of human atherosclerosis

    International Nuclear Information System (INIS)

    Toussaint, J.F.

    1995-01-01

    Diagnosis and prognosis of atherosclerosis can no longer be evaluated with morphological parameters only. A description of atherosclerotic plaque composition is necessary to study the mechanisms of plaque rupture, which depends on collagenous cap and lipid core thicknesses. NMR, as a biochemical imaging technique, allows visualization of these components using T1 contrast (mobile lipids), T2 contrast (cap vs. core), spin density (calcifications), diffusion imaging, 1H and 13C spectroscopy. Today, these imaging sequences allow to study in vitro the effects of interventional techniques such as angioplasty or atherectomy. Clinical investigations begin, which will attempt to develop in vivo microscopy and test the ability of NMR to predict plaque rupture. (author). 13 refs., 7 figs

  18. Aging, Atherosclerosis, and IGF-1

    Science.gov (United States)

    Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung

    2012-01-01

    Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1–induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging. PMID:22491965

  19. Effect of blood UV-irradiation on the development of alimentary cholesterol atherosclerosis in rabbits (preliminary data)

    International Nuclear Information System (INIS)

    Chernigovskaya, S.V.; Yanushkene, T.S.

    1986-01-01

    In-house and literature data on possible effect of autotransfusion of UV-irradiated blood (AUVIB) on the development of hypercholesterolemia in rabbits and degree of ateriosclerotic change manifestation in the aorta of the animals are discussed

  20. Pathogenetics aspects of relationship mouth infectious diseases with development and progression atherosclerosis and possibility for their integrated prevention

    Directory of Open Access Journals (Sweden)

    M. V. Avdeeva

    2012-01-01

    Full Text Available The article contains the modern literature data about impact of various infectious agents on the development and progression of atherosclerotic disease. The data are demonstrated the role of various infectious diseases, including periodontal diseases, in the development of biological degradation and destabilization of atherosclerotic plaques. The article questions of organization of primary prevention of cardiovascular disease based on the screening assessment by stomatologist the oral sanitary status. Necessary to carry out sanitation of chronic infection foci of the mouth on the basis of existing children’s health centers. The children’s health centers have a set of dental equipment, with which can perform a screening diagnosis of dental caries, periodontal diseases, non-carious lesions, diseases of the mucous membranes, and conduct preventive oral sanitation. The duties of dental hygienists is teaching children of different age groups to the rules of oral care, demonstration of skills, brushing teeth, information about the importance of prevention of dental caries and periodontal disease, as it is not only important for the preservation of the teeth, but also may prevent the development of ardiovasculardisease adulthood.

  1. Molecular Imaging of Inflammation in Atherosclerosis

    Science.gov (United States)

    Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

    2013-01-01

    Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

  2. Enterprise strategic development under conditions of uncertainty

    Directory of Open Access Journals (Sweden)

    O.L. Truhan

    2016-09-01

    Full Text Available The author points out the necessity to conduct researches in the field of enterprise strategic development under conditions of increased dynamism and uncertainty of external environment. It is determined that under conditions of external uncertainty it’s reasonable to conduct the strategic planning of entities using the life cycle models of organization and planning on the basis of disclosure. Any organization has to react in a flexible way upon external calls applying the cognitive knowledge about its own business model of development and the ability to intensify internal working reserves. The article determines that in the process of long-term business activity planning managers use traditional approaches based on the familiar facts and conditions that the present tendencies will not be subjected to essential changes in the future. Planning a new risky business one has to act when prerequisites and assumptions are predominant over knowledge. The author proves that under such conditions the powerful tool of enterprise strategic development may be such a well-known approach as “planning on the basis of disclosure”. The approach suggested helps take into account numerous factors of uncertainty of external environment that makes the strategic planning process maximum adaptable to the conditions of venture business development.

  3. Decisions on new product development under uncertainties

    Science.gov (United States)

    Huang, Yeu-Shiang; Liu, Li-Chen; Ho, Jyh-Wen

    2015-04-01

    In an intensively competitive market, developing a new product has become a valuable strategy for companies to establish their market positions and enhance their competitive advantages. Therefore, it is essential to effectively manage the process of new product development (NPD). However, since various problems may arise in NPD projects, managers should set up some milestones and subsequently construct evaluative mechanisms to assess their feasibility. This paper employed the approach of Bayesian decision analysis to deal with the two crucial uncertainties for NPD, which are the future market share and the responses of competitors. The proposed decision process can provide a systematic analytical procedure to determine whether an NPD project should be continued or not under the consideration of whether effective usage is being made of the organisational resources. Accordingly, the proposed decision model can assist the managers in effectively addressing the NPD issue under the competitive market.

  4. [The receptor theory of atherosclerosis].

    Science.gov (United States)

    Likhoded, V G; Bondarenko, V M; Gintsburg, A L

    2010-01-01

    Lipopolysaccharides of Gram-negative bacteria can interact with Toll-like receptor 4 (TLR4) and induce atheroma formation. The risk of atherosclerosis is decreased in case of TLR4 mutation. Other bacterial ligands and endogenous ligands of TLRs can also be involved in induction of atherogenesis. The general concept of atherosclerosis pathogentsis is presented. According to this concept atherogenesis can be initiated by some reactions resulting from interaction of exogenous and endogenous microbial ligands with Toll-like receptors.

  5. Historical development of derivatives’ underlying assets

    Directory of Open Access Journals (Sweden)

    Sylvie Riederová

    2011-01-01

    Full Text Available The derivative transactions are able to eliminate the unexpected risk arising from the price volatility of the asset. The need for risk elimination relates to the application of derivatives.This paper is focused on derivatives’ underlying assets themselves. With the plain description, supported by progressive summarization, the authors analysed the relevant theoretical sources, dealt with derivatives, their underlying assets and their development in centuries. Starting in the ancient history, 2000 BC, the first non-standard transaction, very close to today’s understanding of derivatives, becomes to be closed between counterparties. During the time, in different kingdoms and emporiums, derivatives started to play a significant role in daily life, helping to reduce the uncertainty of the future. But the real golden era for derivatives started with the so called ‘New derivative markets’ and computer supported trading. They have extended their form from simple tools to most complex structures, without changing their main purpose hedging and risk – reduction.For the main purpose of this paper it is impossible to split the development of derivatives from the very wide extension of underlying assets. The change of these assets was one of the main drivers in derivatives development. Understanding of the dynamic character of these assets helps to understand the world of derivatives.

  6. Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis.

    Science.gov (United States)

    Mulvihill, Erin E; Burke, Amy C; Huff, Murray W

    2016-07-17

    Citrus flavonoids are polyphenolic compounds with significant biological properties. This review summarizes recent advances in understanding the ability of citrus flavonoids to modulate lipid metabolism, other metabolic parameters related to the metabolic syndrome, and atherosclerosis. Citrus flavonoids, including naringenin, hesperitin, nobiletin, and tangeretin, have emerged as potential therapeutics for the treatment of metabolic dysregulation. Epidemiological studies reveal an association between the intake of citrus flavonoid-containing foods and a decreased incidence of cardiovascular disease. Studies in cell culture and animal models, as well as a limited number of clinical studies, reveal the lipid-lowering, insulin-sensitizing, antihypertensive, and anti-inflammatory properties of citrus flavonoids. In animal models, supplementation of rodent diets with citrus flavonoids prevents hepatic steatosis, dyslipidemia, and insulin resistance primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose, kidney, and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established, although several potential targets have been identified. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters as well as through direct impact on the vessel wall. Recent studies support a role for citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity, and atherosclerosis. Larger human studies examining dose, bioavailability, efficacy, and safety are required to promote the development of these promising therapeutic agents.

  7. Nanomedicine highlights in atherosclerosis

    International Nuclear Information System (INIS)

    Karagkiozaki, Varvara

    2013-01-01

    Atherosclerosis is a multifactorial disease and many different approaches have been attempted for its accurate diagnosis and treatment. The disease is induced by a low-grade inflammatory process in the vascular wall, leading through a cascade of events to the eventual formation of atheromatous plaque and arterial stenosis. Different types of cells participate in the process making more difficult to recognize the potential cellular targets within the plaques for their effective treatment. The rise of nanomedicine over the last decade has provided new types of drug delivery nanosystems that are able to be delivered to a specific diseased site of the vessel for imaging while simultaneously act as therapeutic agents. In this paper, a review of the recent advances in nanomedicine that has provided novel insights to the disease diagnosis and treatment will be given in line with different nanotechnology-based approaches to advance the cardiovascular stents. The main complications of bare metal stents such as restenosis and of drug-eluting stents which is the late stent thrombosis are analyzed to comprehend the demand for emerging therapeutic strategies based on nanotechnology.

  8. Nanomedicine highlights in atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Karagkiozaki, Varvara, E-mail: vakaragk@physics.auth.gr [Aristotle University of Thessaloniki, Nanomedicine Group, Laboratory for Thin Films-Nanosystems and Nanometrology (LTFN), Physics Department (Greece)

    2013-04-15

    Atherosclerosis is a multifactorial disease and many different approaches have been attempted for its accurate diagnosis and treatment. The disease is induced by a low-grade inflammatory process in the vascular wall, leading through a cascade of events to the eventual formation of atheromatous plaque and arterial stenosis. Different types of cells participate in the process making more difficult to recognize the potential cellular targets within the plaques for their effective treatment. The rise of nanomedicine over the last decade has provided new types of drug delivery nanosystems that are able to be delivered to a specific diseased site of the vessel for imaging while simultaneously act as therapeutic agents. In this paper, a review of the recent advances in nanomedicine that has provided novel insights to the disease diagnosis and treatment will be given in line with different nanotechnology-based approaches to advance the cardiovascular stents. The main complications of bare metal stents such as restenosis and of drug-eluting stents which is the late stent thrombosis are analyzed to comprehend the demand for emerging therapeutic strategies based on nanotechnology.

  9. Roles and Mechanisms of Obstructive Sleep Apnea-Hypopnea Syndrome and Chronic Intermittent Hypoxia in Atherosclerosis: Evidence and Prospective

    OpenAIRE

    Ma, Linqin; Zhang, Jingchun; Liu, Yue

    2016-01-01

    The morbidity and mortality of obstructive sleep apnea-hypopnea syndrome (OSAHS) are regarded as consequences of its adverse effects on the cardiovascular system. Chronic intermittent hypoxia (CIH) induced by OSAHS can result in vascular endothelial injury, thus promoting development of atherosclerosis (AS). Studies have shown that CIH is an independent risk factor for the occurrence and development of AS, but the underlying mechanism remains unclear. Here, we review clinical and fundamental ...

  10. Periodontal disease and carotid atherosclerosis: A meta-analysis of 17,330 participants.

    Science.gov (United States)

    Zeng, Xian-Tao; Leng, Wei-Dong; Lam, Yat-Yin; Yan, Bryan P; Wei, Xue-Mei; Weng, Hong; Kwong, Joey S W

    2016-01-15

    The association between periodontal disease and carotid atherosclerosis has been evaluated primarily in single-center studies, and whether periodontal disease is an independent risk factor of carotid atherosclerosis remains uncertain. This meta-analysis aimed to evaluate the association between periodontal disease and carotid atherosclerosis. We searched PubMed and Embase for relevant observational studies up to February 20, 2015. Two authors independently extracted data from included studies, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for overall and subgroup meta-analyses. Statistical heterogeneity was assessed by the chi-squared test (Pperiodontal disease was associated with carotid atherosclerosis (OR: 1.27, 95% CI: 1.14-1.41; Pperiodontal disease was associated with carotid atherosclerosis; however, further large-scale, well-conducted clinical studies are needed to explore the precise risk of developing carotid atherosclerosis in patients with periodontal disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Carbon monoxide, smoking, and atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Astrup, P

    1973-10-01

    Studies on the effects of carbon monoxide and smoking on atherosclerosis are reviewed. Nonsmokers do not run the risk of getting significantly elevated carboxyhemoglobin levels from automobile exhaust in the streets, however, they do run the risk of getting elevated carboxyhemoglobin levels from exposure to CO in closed areas such as garages and tunnels. Carboxyhemoglobin levels up to 20 percent may also be found in smokers. The central nervous system seems to be influenced by carboxyhemoglobin concentrations up to 20 percent. The myocardium may also be affected. Experimental work with rabbits exposed to carbon monoxide and cholesterol is described which proved that CO has a damaging effect on arterial walls, leading to increased permeability for various plasma components, to the formation of subendothelial edema, and to increased atheromatosis. The results indicate that the much higher risk of smokers of developing arterial disease in comparison to nonsmokers is mainly due to the inhaled CO in the tobacco smoke and not to nicotine. (Air Pollut. Abstr.)

  12. Noninvasive assessment of preclinical atherosclerosis

    Directory of Open Access Journals (Sweden)

    Helen A Lane

    2006-03-01

    Full Text Available Helen A Lane, Jamie C Smith, J Stephen DaviesDepartment of Endocrinology, University of Wales College of Medicine, Heath Park, Cardiff, Wales, UKAbstract: Initially considered as a semipermeable barrier separating lumen from vessel wall, the endothelium is now recognised as a complex endocrine organ responsible for a variety of physiological processes vital for vascular homeostasis. These include the regulation of vascular tone, luminal diameter, and blood flow; hemostasis and thrombolysis; platelet and leucocyte vessel-wall interactions; the regulation of vascular permeability; and tissue growth and remodelling. The endothelium modulates arterial stiffness, which precedes overt atherosclerosis and is an independent predictor of cardiovascular events. Unsurprisingly, dysfunction of the endothelium may be considered as an early and potentially reversible step in the process of atherogenesis and numerous methods have been developed to assess endothelial status and large artery stiffness. Methodology includes flow-mediated dilatation of the brachial artery, assessment of coronary flow reserve, carotid intimamedia thickness, pulse wave analysis, pulse wave velocity, and plethysmography. This review outlines the various modalities, indications, and limitations of available methods to assess arterial dysfunction and vascular risk.Keywords: endothelial function, vascular risk, vascular stiffness

  13. Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: A combined transcriptomics and metabolomics analysis

    NARCIS (Netherlands)

    Kleemann, R.; Verschuren, L.; Erk, M.J. van; Nikolsky, Y.; Cnubben, N.H.P.; Verheij, E.R.; Smilde, A.K.; Hendriks, H.F.J.; Zadelaar, A.S.M.; Smith, G.J.; Kaznacheev, V.; Nikolskaya, T.; Melnikov, A.; Hurt-Camejo, E.; Greef, J. van der; Ommen, B. van; Kooistra, T.

    2007-01-01

    Background: Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we

  14. Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE-/- Mice With Unilateral Renal Artery Stenosis.

    Science.gov (United States)

    Pathak, Alokkumar S; Huang, Jianhua; Rojas, Mauricio; Bazemore, Taylor C; Zhou, Ruihai; Stouffer, George A

    2016-04-03

    Chronic unilateral renal artery stenosis (RAS) causes accelerated atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown. Male ApoE(-/-) mice underwent sham surgery (n=16) or had partial ligation of the right renal artery (n=41) with the ligature being removed 4 days later (D4LR; n=6), 8 days later (D8LR; n=11), or left in place for 90 days (chronic RAS; n=24). Ligature removal at 4 or 8 days resulted in improved renal blood flow, decreased plasma angiotensin II levels, a return of systolic blood pressure to baseline, and increased plasma levels of neutrophil gelatinase associated lipocalin. Chronic RAS resulted in increased lipid staining in the aortic arch (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; Prenal blood flow at either 4 or 8 days after unilateral RAS had a beneficial effect on systolic blood pressure, aortic lipid deposition, and atheroma inflammation. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  15. Is atherosclerosis imaging the most sensitive way to assess patients' risk and the best way to conduct future drug trials? A pros-and-cons debate.

    Science.gov (United States)

    Nanchen, David; Raggi, Paolo

    2017-11-01

    Atherosclerosis imaging has been the focus of intense debate and research for several decades. Among its primary applications are risk stratification of asymptomatic individuals and follow-up of atherosclerosis progression under a variety of treatments designed to retard or regress the development of arterial disease. Although endorsed and supported by many, this approach has been fiercely opposed by several key opinion leaders over the years. Similarly, regulatory agencies have raised a number of objections to resist the approval of new drugs and devices based on surrogate imaging markers. However, there is a large body of evidence in the medical literature that shows that risk stratification is improved with implementation of atherosclerosis imaging. Additionally, numerous lipid-modifying agents have been tested as far as their ability to affect progression of atherosclerosis, and in many cases the information obtained with imaging was in line with the outcome of subsequent clinical trials. This pros-and-cons debate was staged to bring up in a fun and provoking way the main arguments in favour or against the application of atherosclerosis imaging in the main settings described above. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Analysis of the relationship between periodontal disease and atherosclerosis within a local clinical system: a cross-sectional observational pilot study.

    Science.gov (United States)

    Kudo, Chieko; Shin, Wee Soo; Minabe, Masato; Harai, Kazuo; Kato, Kai; Seino, Hiroaki; Goke, Eiji; Sasaki, Nobuhiro; Fujino, Takemasa; Kuribayashi, Nobuichi; Pearce, Youko Onuki; Taira, Masato; Maeda, Hiroshi; Takashiba, Shogo

    2015-09-01

    It has been revealed that atherosclerosis and periodontal disease may have a common mechanism of "chronic inflammation". Several reports have indicated that periodontal infection is related to atherosclerosis, but none have yet reported such an investigation through the cooperation of local clinics. This study was performed in local Japanese clinics to examine the relationship between periodontal disease and atherosclerosis under collaborative medical and dental care. A pilot multicenter cross-sectional study was conducted on 37 medical patients with lifestyle-related diseases under consultation in participating medical clinics, and 79 periodontal patients not undergoing medical treatment but who were seen by participating dental clinics. Systemic examination and periodontal examination were performed at baseline, and the relationships between periodontal and atherosclerosis-related clinical markers were analyzed. There was a positive correlation between LDL-C level and plasma IgG antibody titer to Porphyromonas gingivalis. According to the analysis under adjusted age, at a cut-off value of 5.04 for plasma IgG titer to Porphyromonas gingivalis, the IgG titer was significantly correlated with the level of low-density lipoprotein cholesterol (LDL-C). This study suggested that infection with periodontal bacteria (Porphyromonas gingivalis) is associated with the progression of atherosclerosis. Plasma IgG titer to Porphyromonas gingivalis may be useful as the clinical risk marker for atherosclerosis related to periodontal disease. Moreover, the application of the blood examination as a medical check may lead to the development of collaborative medical and dental care within the local medical clinical system for the purpose of preventing the lifestyle-related disease.

  17. Nuclear power for under-developed areas

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1959-07-15

    In evaluating the needs of the less developed countries for nuclear power and in determining how and to what extent these needs can be met, the fundamental questions to be decided are: (a) to what extent can the total power needs of these countries be met by conventional (thermal and hydro) means, (b) in which sectors would it be immediately possible - from both technical and economic points of view - to generate power from nuclear energy, and (c) in which areas would it be imperative to resort to nuclear power in the immediate future. The IAEA Second General Conference recommended a survey of the nuclear power needs of the less developed countries, a study on a continuing basis of the technology and economics of small and medium power reactors suited to these countries, dissemination of the information obtained and assistance in training personnel in the technology and economic utilization of such nuclear stations. And on the basis of this recommendation, the Agency has initiated an integrated two-year programme of work for examining the possibilities of utilizing nuclear power in under-developed countries. In carrying out this programme, the Agency is seeking potentially promising cases in which nuclear energy can yield necessarily limited but early benefits. That would help an assessment of the technical and economic possibilities of small and medium reactors in specific situations. It would also enable under-developed countries to compare and ascertain whether nuclear energy can provide an early solution to some of their pressing power problems. The first three phases of IAEA's work programme are: (i) studies on the technical suitability of reactors with a power level of up to 50 mw; (ii) economic studies in regard to reactor systems, including a systematic analysis of power costs; and (iii) selection of characteristic situations that appear to favour utilization of nuclear power. A survey of special interest in this connexion will be carried out by an Agency

  18. Nuclear power for under-developed areas

    International Nuclear Information System (INIS)

    1959-01-01

    In evaluating the needs of the less developed countries for nuclear power and in determining how and to what extent these needs can be met, the fundamental questions to be decided are: (a) to what extent can the total power needs of these countries be met by conventional (thermal and hydro) means, (b) in which sectors would it be immediately possible - from both technical and economic points of view - to generate power from nuclear energy, and (c) in which areas would it be imperative to resort to nuclear power in the immediate future. The IAEA Second General Conference recommended a survey of the nuclear power needs of the less developed countries, a study on a continuing basis of the technology and economics of small and medium power reactors suited to these countries, dissemination of the information obtained and assistance in training personnel in the technology and economic utilization of such nuclear stations. And on the basis of this recommendation, the Agency has initiated an integrated two-year programme of work for examining the possibilities of utilizing nuclear power in under-developed countries. In carrying out this programme, the Agency is seeking potentially promising cases in which nuclear energy can yield necessarily limited but early benefits. That would help an assessment of the technical and economic possibilities of small and medium reactors in specific situations. It would also enable under-developed countries to compare and ascertain whether nuclear energy can provide an early solution to some of their pressing power problems. The first three phases of IAEA's work programme are: (i) studies on the technical suitability of reactors with a power level of up to 50 mw; (ii) economic studies in regard to reactor systems, including a systematic analysis of power costs; and (iii) selection of characteristic situations that appear to favour utilization of nuclear power. A survey of special interest in this connexion will be carried out by an Agency

  19. Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-κB-mediated inflammation in macrophages.

    Science.gov (United States)

    Wang, Ying; Wang, Gary Z; Rabinovitch, Peter S; Tabas, Ira

    2014-01-31

    Mitochondrial oxidative stress (mitoOS) has been shown to correlate with the progression of human atherosclerosis. However, definitive cell type-specific causation studies in vivo are lacking, and the molecular mechanisms of potential proatherogenic effects remain to be determined. Our aims were to assess the importance of macrophage mitoOS in atherogenesis and to explore the underlying molecular mechanisms. We first validated Western diet-fed Ldlr(-/-) mice as a model of human mitoOS-atherosclerosis association by showing that non-nuclear oxidative DNA damage, a marker of mitoOS in lesional macrophages, correlates with aortic root lesion development. To investigate the importance of macrophage mitoOS, we used a genetic engineering strategy in which the OS suppressor catalase was ectopically expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages was successfully suppressed in these mice, and this led to a significant reduction in aortic root lesional area. The mCAT lesions had less monocyte-derived cells, less Ly6c(hi) monocyte infiltration into lesions, and lower levels of monocyte chemotactic protein-1. The decrease in lesional monocyte chemotactic protein-1 was associated with the suppression of other markers of inflammation and with decreased phosphorylation of RelA (NF-κB p65), indicating decreased activation of the proinflammatory NF-κB pathway. Using models of mitoOS in cultured macrophages, we showed that mCAT suppressed monocyte chemotactic protein-1 expression by decreasing the activation of the IκB-kinase β-RelA NF-κB pathway. MitoOS in lesional macrophages amplifies atherosclerotic lesion development by promoting NF-κB-mediated entry of monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis link in human atheromata, these findings reveal a potentially new therapeutic target to prevent the progression of atherosclerosis.

  20. Heme oxygenase-1, oxidation, inflammation and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jesus A Araujo

    2012-07-01

    Full Text Available Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1 is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of heme oxygenase, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This article reviews the evidence that supports the antiatherogenic role of HO-1, potential pathways and mechanisms mediating

  1. Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice : An immunohistochemical study

    NARCIS (Netherlands)

    Gijbels, M.J.J.; Cammen, M. van der; Laan, L.J.W. van der; Emeis, J.J.; Havekes, L.M.; Hofker, M.H.; Kraal, G.

    1999-01-01

    Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study

  2. Risk factors for atherosclerosis - can they be used to identify the ...

    African Journals Online (AJOL)

    Risk factors are often used in preventive care programmes to identify the patient at particular risk for developing atherosclerosis. Risk factors for atherosclerosis have also been shown to be linked to the presence of the disease at a given time, a fact that may be helpful when screening for additional atherosclerotic disease in ...

  3. Models and Analysis of Atherosclerosis, Restenosis, and Aneurysm Formation in the Mouse

    NARCIS (Netherlands)

    de Waard, Vivian; Gijbels, Marion J. J.; Lutgens, Esther; de Winther, Menno P. J.; de Vries, Carlie J. M.

    2012-01-01

    Atherosclerosis is considered a chronic inflammatory condition of the vessel wall and involves a high chronic concentration of low-density lipoprotein (LDL) in blood. In humans, restenosis develops after intravascular interventions such as angioplasty and stent placement to treat atherosclerosis,

  4. Immunoproteasome subunit ß5i/LMP7-deficiency in atherosclerosis.

    Science.gov (United States)

    Hewing, Bernd; Ludwig, Antje; Dan, Cristian; Pötzsch, Max; Hannemann, Carmen; Petry, Andreas; Lauer, Dilyara; Görlach, Agnes; Kaschina, Elena; Müller, Dominik N; Baumann, Gert; Stangl, Verena; Stangl, Karl; Wilck, Nicola

    2017-10-17

    Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit β5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of β5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR -/- LMP7 -/- and LDLR -/- mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively. Lesion burden was similar between genotypes in both stages. Macrophage content and abundance of polyubiquitin conjugates in aortic root plaques were unaltered by β5i/LMP7-deficiency. In vitro experiments using bone marrow-derived macrophages (BMDM) showed that β5i/LMP7-deficiency did not influence macrophage polarization or accumulation of polyubiquitinated proteins and cell survival upon hydrogen peroxide and interferon-γ treatment. Analyses of proteasome core particle composition by Western blot revealed incorporation of standard proteasome subunits in β5i/LMP7-deficient BMDM and spleen. Chymotrypsin-, trypsin- and caspase-like activities assessed by using short fluorogenic peptides in BMDM whole cell lysates were similar in both genotypes. Taken together, deficiency of IP subunit β5i/LMP7 does not disturb protein homeostasis and does not aggravate atherogenesis in LDLR -/- mice.

  5. Suppression of atherosclerosis by synthetic REV-ERB agonist

    Energy Technology Data Exchange (ETDEWEB)

    Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  6. [Evolution of pathogenesis of atherosclerosis in phylogenesis].

    Science.gov (United States)

    Titov, V N

    2014-01-01

    The first atherosclerosis pandemics developed in phylogenesis when animals went out of the ocean, the second coincided with mutations of proteins that transferred zero-cholesterol esters, the third (present-day pandemics) results from disturbed biological function of trophology, abnormally high content of saturated fatty acids and their trans-forms in food, and blockade of bioavailability of polyenic FA (PNFA) for cells. The blood pool of ligand-free lipoproteins, phylogenetically early macrophages are only partly utilized in intima giving rise to atheromatosis. When active absorption of w-3 and w-6 PNFA is blocked, the cells synthesize by way of compensation non-physiological w-9 eicosanoids which creates the basis of pathogenesis of atherosclerosis, pathology ofautocrine regulation, and paracrine humoral regulation of cell communities and the body. A rise in the frequency of non-infectious diseases above 5-7% is regarded as pathology of biological functions and reactions. Non-physiological environmental effects should be neutralized by normalization of tropholgy function, exotrophic biological reaction. Metabolic pandemics may have two outcomes. First: (a) effective reduction to a minimum of infavourable environmental effects, i.e. normalization of the nutritive function, (b) matching it with possibilities of lipoproteins, (c) reduction of morbidity and mortality from atherosclerosis. Second: man continues to develop as in phylogenesis and adapts himself to nonphysiological nutrition. Mortality from infarction and stroke will remain high during the next 40-50 thousand years. Increased content of w-3 PNFA in food without reduction of NAF with blockade of bioavailability will further facilitate atheromatosis. Man should rely on physiological nutrition, there is no reason to rely on hypolipidemic agents. Otherwise, the second outcome awaits the mankind. Tertium non datum.

  7. Intranasal delivery of E-selectin reduces atherosclerosis in ApoE-/- mice.

    Directory of Open Access Journals (Sweden)

    Xinhui Li

    Full Text Available Mucosal tolerance to E-selectin prevents stroke and protects against ischemic brain damage in experimental models of stroke studying healthy animals or spontaneously hypertensive stroke-prone rats. A reduction in inflammation and neural damage was associated with immunomodulatory or "tolerogenic" responses to E-selectin. The purpose of the current study on ApoE deficient mice is to assess the capacity of this stroke prevention innovation to influence atherosclerosis, a major underlying cause for ischemic strokes; human E-selectin is being translated as a potential clinical prevention strategy for secondary stroke. Female ApoE-/- mice received intranasal delivery of E-selectin prior to (pre-tolerization or simultaneously with initiation of a high-fat diet. After 7 weeks on the high-fat diet, lipid lesions in the aorta, serum triglycerides, and total cholesterol were assessed as markers of atherosclerosis development. We also assessed E-selectin-specific antibodies and cytokine responses, in addition to inflammatory responses that included macrophage infiltration of the aorta and altered gene expression profiles of aortic mRNA. Intranasal delivery of E-selectin prior to initiation of high-fat chow decreased atherosclerosis, serum total cholesterol, and expression of the leucocyte chemoattractant CCL21 that is typically upregulated in atherosclerotic lesions of ApoE-/- mice. This response was associated with the induction of E-selectin specific cells producing the immunomodulatory cytokine IL-10 and immunosuppressive antibody isotypes. Intranasal administration of E-selectin generates E-selectin specific immune responses that are immunosuppressive in nature and can ameliorate atherosclerosis, a major risk factor for ischemic stroke. These results provide additional preclinical support for the potential of induction of mucosal tolerance to E-selectin to prevent stroke.

  8. Redox balance and blood elemental levels in atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Napoleao, P. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal) and Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. no 10, 2685-953 Sacavem (Portugal)]. E-mail: pnapoleao@itn.pt; Lopes, P.A. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal); Santos, M. [Centro de Quimica e Bioquimica and Departamento de Quimica e Bioquimica, Faculdade de Ciencias de Lisboa, 1749-016 Lisbon (Portugal); Steghens, J.-P. [Federation de Biochimie, Hopital Edouard Herriot, 3 Place d' Arsonval, 69437 03 Lyon (France); Viegas-Crespo, A.M. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal); Pinheiro, T. [Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. no 10, 2685-953 Sacavem (Portugal); Centro de Fisica Nuclear, Universidade de Lisboa, Av. Prof. Egas Moniz, 1700 Lisbon (Portugal)

    2006-08-15

    Oxidation of lipids and proteins represents a causative event for atherogenesis, which can be opposed by antioxidant activity. Elements, such as, Fe, Cu, Zn and Se can be involved in both mechanisms. Thus, evaluation of blood elemental levels, easily detected by PIXE, and of redox parameters may be useful in assessing the risk of atherosclerosis. A group of stable patients suffering from atherosclerosis, was matched with a cohort of normo-tensive and -lipidemic volunteers. Although no major discrepancies were observed for trace elemental levels in blood, increased concentrations of K and Ca were found in atherosclerotic group. Patients presented enhance levels of antioxidant ({alpha}-tocopherol) and decreased of protein oxidation (protein carbonyls), while for the lipid oxidation marker (malondialdehyde) no variation was observed. This study contributes to a better understanding of atherosclerosis development and its relationship with blood elemental levels, and set basis for further clinical trials with pathological groups in acute phase.

  9. Atherosclerosis in familial lines of pigeons fed exogenous cholesterol.

    Science.gov (United States)

    Patton, N M; Brown, R V; Middleton, C C

    1975-01-01

    Exogenous cholesterol was fed to F1 pigeons of high and low serum cholesterol differentiated lines of White Carneau and Racing Homer pigeons that had previously been developed by selection and positive assortive mating. The serum cholesterol response of the various high and low lines was dependent upon the breed and the amount of cholesterol in the diet. Racing Homer pigeons were found to be more resistant to aortic atherosclerosis and more susceptible to coronary atherosclerosis than White Carneau pigeons. Data from necropsy examinations showed significant differences in both aortic and coronary atherosclerosis between lines within the White Carneau breed, but no differences between lines of the Racing Homer breed. Mean organ weights for the 4 lines of pigeons were reported.

  10. Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis

    Directory of Open Access Journals (Sweden)

    Yuri V. Bobryshev

    2016-01-01

    Full Text Available Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances.

  11. Nanomedicine for the prevention, treatment and imaging of atherosclerosis.

    Science.gov (United States)

    Psarros, Costas; Lee, Regent; Margaritis, Marios; Antoniades, Charalambos

    2012-09-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in developed countries, with an increasing prevalence due to an aging population. The pathology underpinning CVD is atherosclerosis, a chronic inflammatory state involving the arterial wall. Accumulation of low density lipoprotein (LDL) laden macrophages in the arterial wall and their subsequent transformation into foam cells lead to atherosclerotic plaque formation. Progression of atherosclerotic lesions may gradually lead to plaque related complications and clinically manifest as acute vascular syndromes including acute myocardial or cerebral ischemia. Nanotechnology offers emerging therapeutic strategies, which may have advantage overclassical treatments for atherosclerosis. In this review, we present the potential applications of nanotechnology toward prevention, identification and treatment of atherosclerosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.

    Science.gov (United States)

    Yuan, Xiying; Yang, Xiaorong; Cai, Danning; Mao, Dan; Wu, Jie; Zong, Li; Liu, Jingjing

    2008-07-04

    In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, pnanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, pintramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

  13. Probiotics and atherosclerosis – a new challenge?

    Directory of Open Access Journals (Sweden)

    Chan Yee Kwan

    2012-06-01

    Full Text Available Background Atherosclerosis is the major cause of cardiovascular disease and stroke, which are among the top 10 leading causes of death worldwide. Pathogen-associated molecular patterns (PAMPs can activate toll-like receptors (TLRs and activate nuclear factor kappa B (NFκB signaling, a central pathway in inflammation, which regulates genes that encode proinflammatory molecules essential in atherogenesis. Lipopolysaccharides (LPS, which is unique to gram negative bacteria, as well as peptidoglycan (PGN, which is found in gram positive bacteria are PAMPS and ligands of TLR4 and TLR2, respectively, both of which are essential in plaque progression in atherosclerosis. Gastrointestinal tract is suggested to be the major site for absorption and translocation of TLR2 and TLR4 stimulants. Inflammation can result in a ‘leaky gut’ that leads to higher bacterial translocation, eventually the accumulation of LPS and PGN would activate TLRs and trigger inflammation through NFκB and promote further systemic complication like atherosclerosis. Probiotics, can protect the intestinal barrier to reduce bacterial translocation and have potential systemic anti-inflammatory properties.To evaluate whether probiotics can help reduce atherosclerotic development using in vivo study.Apolipoprotein E knockout (ApoE−/ −  mice were fed on high fat diet alone, with telmisartan (Tel (1 or 5 mg/kg/day, positive controls or with probiotics (VSL#3/LGG with or without Tel (1 mg/kg/day for 12 weeks.Probiotics, Tel, or a combination of both reduced lesion size at the aortic root significantly; VSL#3 reduced serum inflammatory adhesion molecules soluble E- (sE-selectin, soluble intercellular adhesion molecule 1 (sICAM-1, soluble vascular cell adhesion molecule 1 (sVCAM-1, and plaque disrupting factor matrix metalloproteinase (MMP-9 significantly; probiotics and Tel at 5 mg/kg/day could induce changes in gut microbiota population; the efficiency of lesion reduction seemed

  14. Cardiovascular risk scores for coronary atherosclerosis.

    Science.gov (United States)

    Yalcin, Murat; Kardesoglu, Ejder; Aparci, Mustafa; Isilak, Zafer; Uz, Omer; Yiginer, Omer; Ozmen, Namik; Cingozbay, Bekir Yilmaz; Uzun, Mehmet; Cebeci, Bekir Sitki

    2012-10-01

    The objective of this study was to compare frequently used cardiovascular risk scores in predicting the presence of coronary artery disease (CAD) and 3-vessel disease. In 350 consecutive patients (218 men and 132 women) who underwent coronary angiography, the cardiovascular risk level was determined using the Framingham Risk Score (FRS), the Modified Framingham Risk Score (MFRS), the Prospective Cardiovascular Münster (PROCAM) score, and the Systematic Coronary Risk Evaluation (SCORE). The area under the curve for receiver operating characteristic curves showed that FRS had more predictive value than the other scores for CAD (area under curve, 0.76, P MFRS, PROCAM, and SCORE) may predict the presence and severity of coronary atherosclerosis.The FRS had better predictive value than the other scores.

  15. Periodontitis as a Risk Factor of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jirina Bartova

    2014-01-01

    Full Text Available Over the last two decades, the amount of evidence corroborating an association between dental plaque bacteria and coronary diseases that develop as a result of atherosclerosis has increased. These findings have brought a new aspect to the etiology of the disease. There are several mechanisms by which dental plaque bacteria may initiate or worsen atherosclerotic processes: activation of innate immunity, bacteremia related to dental treatment, and direct involvement of mediators activated by dental plaque and involvement of cytokines and heat shock proteins from dental plaque bacteria. There are common predisposing factors which influence both periodontitis and atherosclerosis. Both diseases can be initiated in early childhood, although the first symptoms may not appear until adulthood. The formation of lipid stripes has been reported in 10-year-old children and the increased prevalence of obesity in children and adolescents is a risk factor contributing to lipid stripes development. Endothelium damage caused by the formation of lipid stripes in early childhood may lead to bacteria penetrating into blood circulation after oral cavity procedures for children as well as for patients with aggressive and chronic periodontitis.

  16. Innate lymphoid cells in atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Lichtman, Andrew H

    2017-12-05

    The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

  17. Development of a Patient-Specific Multi-Scale Model to Understand Atherosclerosis and Calcification Locations: Comparison with In vivo Data in an Aortic Dissection

    Science.gov (United States)

    Alimohammadi, Mona; Pichardo-Almarza, Cesar; Agu, Obiekezie; Díaz-Zuccarini, Vanessa

    2016-01-01

    Vascular calcification results in stiffening of the aorta and is associated with hypertension and atherosclerosis. Atherogenesis is a complex, multifactorial, and systemic process; the result of a number of factors, each operating simultaneously at several spatial and temporal scales. The ability to predict sites of atherogenesis would be of great use to clinicians in order to improve diagnostic and treatment planning. In this paper, we present a mathematical model as a tool to understand why atherosclerotic plaque and calcifications occur in specific locations. This model is then used to analyze vascular calcification and atherosclerotic areas in an aortic dissection patient using a mechanistic, multi-scale modeling approach, coupling patient-specific, fluid-structure interaction simulations with a model of endothelial mechanotransduction. A number of hemodynamic factors based on state-of-the-art literature are used as inputs to the endothelial permeability model, in order to investigate plaque and calcification distributions, which are compared with clinical imaging data. A significantly improved correlation between elevated hydraulic conductivity or volume flux and the presence of calcification and plaques was achieved by using a shear index comprising both mean and oscillatory shear components (HOLMES) and a non-Newtonian viscosity model as inputs, as compared to widely used hemodynamic indicators. The proposed approach shows promise as a predictive tool. The improvements obtained using the combined biomechanical/biochemical modeling approach highlight the benefits of mechanistic modeling as a powerful tool to understand complex phenomena and provides insight into the relative importance of key hemodynamic parameters. PMID:27445834

  18. Epigenetic pathways in macrophages emerge as novel targets in atherosclerosis

    NARCIS (Netherlands)

    Neele, Annette E.; van den Bossche, Jan; Hoeksema, Marten A.; de Winther, Menno P. J.

    2015-01-01

    Atherosclerosis is a lipid-driven chronic inflammatory disorder. Monocytes and macrophages are key immune cells in the development of disease and clinical outcome. It is becoming increasingly clear that epigenetic pathways govern many aspects of monocyte and macrophage differentiation and

  19. Intra‑operative grading of coronary artery atherosclerosis associated ...

    African Journals Online (AJOL)

    Background: Atherosclerosis is one of the common causes of morbidity and mortality, in postmenopausal women. Homocysteine, a sulfur‑containing amino acid product of methionine metabolism, may play an important role in the development of cardiovascular diseases. This study was designed to evaluate the relationship ...

  20. Premature atherosclerosis after treatment for acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Elżbieta Sadurska

    2018-03-01

    Survivors of childhood ALL in the examined group demonstrated elevated concentrations of selected new biomarkers and increased IMT values, compared to controls, which may confirm the occurrence of endothelial injuries in blood vessels. This study indicates that subjects treated for childhood malignancy are at a higher risk of prematurely developing atherosclerosis.

  1. Transportation strategy development under economic uncertainty.

    Science.gov (United States)

    2013-05-01

    The interests of the researchers here were to understand various modes for developing long term : that is strategic plans with particular concern for the economic uncertainties one invariably : faces in such a planning environment. Often resou...

  2. Island development: Local governance under globalization

    Directory of Open Access Journals (Sweden)

    Huei-Min Tsai

    2014-12-01

    Full Text Available Issues surrounding island development have generated a growing volume of research. What does it mean to develop? How can island communities maintain control over development processes to the benefit of the local economy, rather than seeing economic flows enter and exit the island with little or a primarily negative impact? And how important is local knowledge for edifying local governance and enhancing potentials for innovation in island development? Island histories have repeatedly been forwarded as exemplars and ‘lessons’ for global learning on (unsustainability. To consider these issues, we have selected a number of papers from among the presentations given at the International Geographical Union’s Commission on Islands Conference, Island Development: Local Economy, Culture, Innovation and Sustainability, which took place in the Penghu Archipelago, Taiwan, 1–5 October 2013. These papers serve as examples of how the processes of globalization have penetrated the borders and changed the political and economic structures of islands. They also explore how island-based innovations in science, technology, culture, and formal or informal governance might contribute to sustainable island development.

  3. System development and asset management under restructuring

    International Nuclear Information System (INIS)

    2007-01-01

    In many developed countries the electricity infrastructure contains ageing assets. Because of the need of a continuing operation and higher load factors on the network, the opportunities for replacement or refurbishment are limited. These must be regarded as an opportunity to review the structure of the system and to consider the design and development required to meet the new requirements, taking advantage of new available technologies: HVDC, FACTS, cables, etc. The symposium examines assets management issues and assesses strategies for overhauling existing systems, taking into account the impact on market operation, on supply security and environment

  4. ALUminating the Path of Atherosclerosis Progression: Chaos Theory Suggests a Role for Alu Repeats in the Development of Atherosclerotic Vascular Disease.

    Science.gov (United States)

    Hueso, Miguel; Cruzado, Josep M; Torras, Joan; Navarro, Estanislao

    2018-06-12

    Atherosclerosis (ATH) and coronary artery disease (CAD) are chronic inflammatory diseases with an important genetic background; they derive from the cumulative effect of multiple common risk alleles, most of which are located in genomic noncoding regions. These complex diseases behave as nonlinear dynamical systems that show a high dependence on their initial conditions; thus, long-term predictions of disease progression are unreliable. One likely possibility is that the nonlinear nature of ATH could be dependent on nonlinear correlations in the structure of the human genome. In this review, we show how chaos theory analysis has highlighted genomic regions that have shared specific structural constraints, which could have a role in ATH progression. These regions were shown to be enriched with repetitive sequences of the Alu family, genomic parasites that have colonized the human genome, which show a particular secondary structure and are involved in the regulation of gene expression. Here, we show the impact of Alu elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms via which the Alu elements alter the inflammatory response. We devote special attention to their relationship with the long noncoding RNA (lncRNA); antisense noncoding RNA in the INK4 locus ( ANRIL ), a risk factor for ATH; their role as microRNA (miRNA) sponges; and their ability to interfere with the regulatory circuitry of the (nuclear factor kappa B) NF-κB response. We aim to characterize ATH as a nonlinear dynamic system, in which small initial alterations in the expression of a number of repetitive elements are somehow amplified to reach phenotypic significance.

  5. [Transdisciplinary Approach for Sarcopenia. Sarcopenia and atherosclerosis].

    Science.gov (United States)

    Kohara, Katsuhiko

    2014-10-01

    Risk factors for sarcopenia, including aging, inflammation, oxidative stress, and sedentary life style, are also known as risks for atherosclerosis. Sarcopenia and atherosclerosis relate each other. We found that sarcopenia, especially sarcopenic visceral obesity in male subjects, was associated with higher arterial stiffness and central blood pressure. We also observed that leptin resistance may underlie the link between sarcopenia, sarcopenic obesity and atherosclerosis. In epidemiological studies, it has been demonstrated sarcopenic indices were associated with cardiovascular death. These findings indicate that sarcopenia could be regarded as risk factor for atherosclerosis and cardiovascular events.

  6. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  7. Neural Development Under Conditions of Spaceflight

    Science.gov (United States)

    Kosik, Kenneth S.; Steward, Oswald; Temple, Meredith D.; Denslow, Maria J.

    2003-01-01

    One of the key tasks the developing brain must learn is how to navigate within the environment. This skill depends on the brain's ability to establish memories of places and things in the environment so that it can form cognitive maps. Earth's gravity defines the plane of orientation of the spatial environment in which animals navigate, and cognitive maps are based on this plane of orientation. Given that experience during early development plays a key role in the development of other aspects of brain function, experience in a gravitational environment is likely to be essential for the proper organization of brain regions mediating learning and memory of spatial information. Since the hippocampus is the brain region responsible for cognitive mapping abilities, this study evaluated the development of hippocampal structure and function in rats that spent part of their early development in microgravity. Litters of male and female Sprague-Dawley rats were launched into space aboard the Space Shuttle Columbia on either postnatal day eight (P8) or 14 (P14) and remained in space for 16 days. Upon return to Earth, the rats were tested for their ability to remember spatial information and navigate using a variety of tests (the Morris water maze, a modified radial arm maze, and an open field apparatus). These rats were then tested physiologically to determine whether they exhibited normal synaptic plasticity in the hippocampus. In a separate group of rats (flight and controls), the hippocampus was analyzed using anatomical, molecular biological, and biochemical techniques immediately postlanding. There were remarkably few differences between the flight groups and their Earth-bound controls in either the navigation and spatial memory tasks or activity-induced synaptic plasticity. Microscopic and immunocytochemical analyses of the brain also did not reveal differences between flight animals and ground-based controls. These data suggest that, within the developmental window

  8. Premature atherosclerosis: Sounds familial?

    NARCIS (Netherlands)

    Mulders, T.A.

    2013-01-01

    The prevention of cardiovascular disease is an important challenge in current medical practice. Despite higher event rates and cardiovascular burden in individuals at a more advanced age, it represents a greater challenge in individuals who develop cardiovascular disease at a very young age. In

  9. Remnant lipoproteins and atherosclerosis

    NARCIS (Netherlands)

    Twickler, Th. B.; Dallinga-Thie, G. M.; Chapman, M. J.; Cohn, J. S.

    2005-01-01

    A recently developed assay for quantification of remnant-like particle cholesterol has provided considerable evidence that reinforces the concept that elevated levels of plasma remnants are associated with increased cardiovascular disease in different populations and distinct patient groups. In this

  10. Nutraceuticals as therapeutic agents for atherosclerosis.

    Science.gov (United States)

    Moss, Joe W E; Williams, Jessica O; Ramji, Dipak P

    2018-05-01

    Atherosclerosis, a chronic inflammatory disorder of medium and large arteries and an underlying cause of cardiovascular disease (CVD), is responsible for a third of all global deaths. Current treatments for CVD, such as optimized statin therapy, are associated with considerable residual risk and several side effects in some patients. The outcome of research on the identification of alternative pharmaceutical agents for the treatment of CVD has been relatively disappointing with many promising leads failing at the clinical level. Nutraceuticals, products from food sources with health benefits beyond their nutritional value, represent promising agents in the prevention of CVD or as an add-on therapy with current treatments. This review will highlight the potential of several nutraceuticals, including polyunsaturated fatty acids, flavonoids and other polyphenols, as anti-CVD therapies based on clinical and pre-clinical mechanism-based studies. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  11. A review of plant-based compounds and medicinal plants effective on atherosclerosis

    Directory of Open Access Journals (Sweden)

    Mehrnoosh Sedighi

    2017-01-01

    Full Text Available Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications.

  12. Oxyradical Stress, Endocannabinoids, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Anberitha T. Matthews

    2015-12-01

    Full Text Available Atherosclerosis is responsible for most cardiovascular disease (CVD and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress. In addition to inflammation and ROS, the endocannabinoid system (eCB is also important in atherogenesis. Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis. For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects. The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG. Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress. This review will highlight the role of reactive oxygen species (ROS in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis. In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis. We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology.

  13. Proinflammatory Status, Genetics and Atherosclerosis

    Czech Academy of Sciences Publication Activity Database

    Poledne, R.; Lorenzová, A.; Stávek, P.; Valenta, Zdeněk; Hubáček, J.; Suchánek, R.; Piťha, J.

    2009-01-01

    Roč. 58, Suppl. 2 (2009), S111-S118 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M06014 Grant - others:GA MŠk(CZ) 1M0510 Program:1M Institutional research plan: CEZ:AV0Z10300504 Keywords : atherosclerosis * inflammation * C-reactive protein * genetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.430, year: 2009 http://www.biomed.cas.cz/physiolres/pdf/58%20Suppl%202/58_S111.pdf

  14. Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis

    Directory of Open Access Journals (Sweden)

    Aoki Toshinari

    2012-01-01

    Full Text Available Abstract Background We analyzed the causal relationship between LDL susceptibility to oxidation and the development of new carotid artery atherosclerosis over a period of 5 years. We previously described the determinants related to a risk of cardiovascular changes determined in a Japanese population participating in the Niigata Study, which is an ongoing epidemiological investigation of the prevention of cardiovascular diseases. Methods We selected 394 individuals (169 males and 225 females who underwent a second carotid artery ultrasonographic examination in 2001 - 2002 for the present study. The susceptibility of LDL to oxidation was determined as the photometric absorbance and electrophoretic mobility of samples that had been collected in 1996 - 1997. The measurements were compared with ultrasonographic findings obtained in 2001 - 2002. Results The multivariate-adjusted model showed that age (odds ratio (OR, 1.034; 95% confidence interval (95%CI, 1.010 - 1.059, HbA1c (OR, 1.477; 95%CI, 0.980 - 2.225, and photometric O/N (OR, 2.012; 95%CI, 1.000 - 4.051 were significant variables that could independently predict the risk of new carotid artery atherosclerosis. Conclusion The susceptibility of LDL to oxidation was a significant parameter that could predict new carotid artery atherosclerosis over a 5-year period, and higher susceptibility was associated with a higher incidence of new carotid artery atherosclerosis.

  15. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, K.B.; Smit, J.W.A.; Heijer, M. den; Middeldorp, S.; Rippe, R.C.; Cessie, S. le; Koning, E.J. de; Jukema, J.W.; Rabelink, T.J.; Roos, A. de; Rosendaal, F.R.; Mutsert, R. de; Assendelft, P.; et al.,

    2013-01-01

    OBJECTIVE: The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  16. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, Karin B.; Smit, Johannes W. A.; den Heijer, Martin; Middeldorp, Saskia; Rippe, Ralph C. A.; le Cessie, Saskia; de Koning, Eelco J. P.; Jukema, J. W.; Rabelink, Ton J.; de Roos, Albert; Rosendaal, Frits R.; de Mutsert, Renée; Rosendaal, F. R.; de Mutsert, R.; Rabelink, T. J.; Smit, J. W. A.; Romijn, J. A.; Rabe, K. F.; de Roos, A.; le Cessie, S.; Hiemstra, P. S.; Kloppenburg, M.; Huizinga, T. W. J.; Pijl, H.; Tamsma, J. T.; de Koning, E. J. P.; Assendelft, W. J. J.; Reitsma, P. H.; van Dijk, K. Willems; de Vries, A. P. J.; Lamb, H. J.; Jazet, I. M.; Dekkers, O. M.; Biermasz, N. R.; Cobbaert, C. M.; Heijer, M. den; Dekker, J. M.; Penninx, B. W.

    2013-01-01

    The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  17. Cell cycle and apoptosis genes in atherosclerosis

    NARCIS (Netherlands)

    Boesten, Lianne Simone Mirjam

    2006-01-01

    The work described in this thesis was aimed at identifying the role of cell cycle and apoptosis genes in atherosclerosis. Atherosclerosis is the primary cause of cardiovascular disease, a disorder occurring in the large and medium-sized arteries of the body. Although in the beginning 90s promising

  18. Regulation of T cell responses in atherosclerosis

    NARCIS (Netherlands)

    Puijvelde, Gijsbrecht Henricus Maria van

    2007-01-01

    One of the most important characteristics of atherosclerosis is the chronic inflammatory response in which T cells and NKT cells are very important. In this thesis several methods to modulate the activity of these T and NKT cells in atherosclerosis are described. The induction of regulatory T cells

  19. In-Vivo Assessment of Coronary Atherosclerosis

    NARCIS (Netherlands)

    G.A. Rodriguez-Granillo

    2006-01-01

    textabstractIntravascular ultrasound (IVUS) has emerged as a highly accurate tool for the serial assessment of the natural history of coronary atherosclerosis and to evaluate the effect of different conventional and emerging drug therapies on the progression of atherosclerosis. The

  20. Role of diabetes, hypertension, and cigarette smoking on atherosclerosis

    OpenAIRE

    Mathur, Ram K.

    2010-01-01

    Hyperosmolar food causes atherosclerosis. Hyperosmolal food hypothesis encompasses all the factors involved under one heading and, that is, the generation of heat in the body. The involvement of cigarette smoking is obvious. High glycemic index food and diabetes result in high levels of blood glucose, which raises the core body temperature. The ingestion of hyperosmolal salt, glucose, and amino acids singularly or synergistically raise the core body temperature, forcing abdominal aorta to for...

  1. Nanotechnology, a new paradigm in atherosclerosis treatment.

    Science.gov (United States)

    Martín Giménez, Virna M; Ruiz-Roso, María Belén; Camargo, Alejandra Beatriz; Kassuha, Diego; Manucha, Walter

    Atherosclerosis, a known and prevalent disease, causes progressive deterioration of affected vessels, inducing a blood flow reduction with different complications, and its symptoms usually manifest in advanced stages of the disease. Therefore, the classic therapeutic alternatives are insufficient because the damages are many times irreversible. For this reason, there is a need to implement intelligent forms of drug administration and develop new therapeutic targets that reduce the progression of atherosclerotic lesion. The implementation of new tools for prevention, diagnosis and treatment of this cardiovascular disease is of special interest, focusing our attention on achieving a more effective control of the immune system. Finally, this review highlights the latest knowledge about nanotechnology as a powerful, modern, and promising therapeutic alternative applied to atherosclerotic disease, as well as warning of the potential complications with their use. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Atherosclerosis

    Science.gov (United States)

    ... usually doesn't cause symptoms until it severely narrows or totally blocks an artery. Many people don't know they have it until they have a medical emergency. A physical exam, imaging, and other diagnostic tests can tell ...

  3. Vascular wall proteoglycan synthesis and structure as a target for the prevention of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Peter J Little

    2007-03-01

    Full Text Available Peter J Little1, 2, 3, Mandy L. Ballinger1, Narin Osman1,31Cell Biology of Diabetes Laboratory, Baker Heart Research Institute, Melbourne, Australia; Monash University, Departments of 2Medicine and 3Immunology, Central and Eastern Clinical School, Alfred Hospital, Melbourne, AustraliaAbstract: Atherosclerosis is the underlying pathology of most cardiovascular disease and it represents the major cause of premature death in modern societies. Current therapies target risk factors being hypertension, hypercholesterolemia, hypertriglyceridemia and hyperglycemia when diabetes is present however the maximum efficacy of these strategies is often 30% or less. Areas of vascular biology that may lead to the development of a complementary vascular wall directed therapy are: inflammation, oxidation, endothelial dysfunction, diabetes-specific factors —hyperglycemia and advanced glycation endproducts and lipid retention by vascular matrix specifically proteoglycans. The major structural features of proteoglycans that determine low-density lipoprotein (LDL binding are the length and sulfation pattern on the glycosaminoglycan (GAG chains. Emerging data discussed in this review indicates that these structural properties are subject to considerable regulation by vasoactive substances possibly using novel signaling pathways. For example, GAG elongation stimulated by platelet-derived growth factor is not blocked by the receptor tyrosine kinase antagonist, genistein suggesting that there may be a previously unknown signaling pathway involved in this response. Thus, modifying proteoglycan synthesis and structure may represent a prime target to prevent LDL binding and entrapment in the vessel wall and thus prevent the development and progression of atherosclerosis.Keywords: proteoglycans, signaling, lipoproteins, atherosclerosis

  4. Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

    Science.gov (United States)

    Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

    2008-10-14

    This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

  5. Natural killer T cells in lipoprotein metabolism and atherosclerosis

    OpenAIRE

    Getz, Godfrey S; VanderLaan, Paul A; Reardon, Catherine A

    2011-01-01

    Cells of both the innate and adaptive immune system participate in the development of atherosclerosis, a chronic inflammatory disorder of medium and large arteries. Natural killer T (NKT) cells express surface markers characteristic of natural killer cells and conventional T cells and bridge the innate and adaptive immune systems. The development and activation of NKT cells is dependent upon CD1d, a MHC-class I-type molecule that presents lipids, especially glycolipids to the TCR on NKT cells...

  6. Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice

    NARCIS (Netherlands)

    Westerterp, M.; Hoogt, C.C. van der; Haan, W. de; Offerman, E.H.; Dallinga-Thie, G.M.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

    2006-01-01

    OBJECTIVE - The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS -

  7. Epigenetic impact of endocrine disrupting chemicals on lipid homeostasis and atherosclerosis: a pregnane X receptor-centric view.

    Science.gov (United States)

    Helsley, Robert N; Zhou, Changcheng

    2017-10-01

    Despite the major advances in developing diagnostic techniques and effective treatments, atherosclerotic cardiovascular disease (CVD) is still the leading cause of mortality and morbidity worldwide. While considerable progress has been achieved to identify gene variations and environmental factors that contribute to CVD, much less is known about the role of "gene-environment interactions" in predisposing individuals to CVD. Our chemical environment has significantly changed in the last few decades, and there are more than 100,000 synthetic chemicals in the market. Recent large-scale human population studies have associated exposure to certain chemicals including many endocrine disrupting chemicals (EDCs) with increased CVD risk, and animal studies have also confirmed that some EDCs can cause aberrant lipid homeostasis and increase atherosclerosis. However, the underlying mechanisms of how exposure to those EDCs influences CVD risk remain elusive. Numerous EDCs can activate the nuclear receptor pregnane X receptor (PXR) that functions as a xenobiotic sensor to regulate host xenobiotic metabolism. Recent studies have demonstrated the novel functions of PXR in lipid homeostasis and atherosclerosis. In addition to directly regulating transcription, PXR has been implicated in the epigenetic regulation of gene transcription. Exposure to many EDCs can also induce epigenetic modifications, but little is known about how the changes relate to the onset or progression of CVD. In this review, we will discuss recent research on PXR and EDCs in the context of CVD and propose that PXR may play a previously unrealized role in EDC-mediated epigenetic modifications that affect lipid homeostasis and atherosclerosis.

  8. Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis

    DEFF Research Database (Denmark)

    Sorensen, Grith L; Bladbjerg, Else Marie; Steffensen, Rudi

    2016-01-01

    OBJECTIVE: Surfactant protein D (SP-D) is a defense collectin with inflammation-modulating properties. SP-D deficiency inhibits atherosclerosis in vivo, and the circulatory SP-D levels have been previously associated with cardiovascular disease mortality. We hypothesized that plasma SP-D (p......SP-D) and SP-D gene (SFTPD) single nucleotide polymorphisms (SNPs) are risk factors for atherosclerosis. METHODS: We evaluated individuals who were all 60 years old and participated in The Glostrup Population Study. Subclinical atherosclerosis was diagnosed based on the ultrasonographic measurement of intima......: The results do not support that pSP-D levels influence the development of subclinical atherosclerosis. However, the SFTPD SNP data support previous observations from animal studies that SP-D plays a role in the etiology of atherosclerotic disease development. The nominal significant effects are likely...

  9. The Progression and Early detection of Subclinical Atherosclerosis (PESA) study

    DEFF Research Database (Denmark)

    Fernández-Ortiz, Antonio; Jiménez-Borreguero, L Jesús; Peñalvo, José L

    2013-01-01

    The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined.......The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined....

  10. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    International Nuclear Information System (INIS)

    Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

    2011-01-01

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 μg/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 μg/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 μg/l). - Highlights: →Arsenic metabolic genes might be associated with carotid atherosclerosis. → A case

  11. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  12. Insights From Pre-Clinical and Clinical Studies on the Role of Innate Inflammation in Atherosclerosis Regression

    Directory of Open Access Journals (Sweden)

    Karishma Rahman

    2018-05-01

    Full Text Available Atherosclerosis, the underlying cause of coronary artery (CAD and other cardiovascular diseases, is initiated by macrophage-mediated immune responses to lipoprotein and cholesterol accumulation in artery walls, which result in the formation of plaques. Unlike at other sites of inflammation, the immune response becomes maladaptive and inflammation fails to resolve. The most common treatment for reducing the risk from atherosclerosis is low density lipoprotein cholesterol (LDL-C lowering. Studies have shown, however, that while significant lowering of LDL-C reduces the risk of heart attacks to some degree, there is still residual risk for the majority of the population. We and others have observed “residual inflammatory risk” of atherosclerosis after plasma cholesterol lowering in pre-clinical studies, and that this phenomenon is clinically relevant has been dramatically reinforced by the recent Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS trial. This review will summarize the role of the innate immune system, specifically macrophages, in atherosclerosis progression and regression, as well as the pre-clinical and clinical models that have provided significant insights into molecular pathways involved in the resolution of plaque inflammation and plaque regression. Partnered with clinical studies that can be envisioned in the post-CANTOS period, including progress in developing targeted plaque therapies, we expect that pre-clinical studies advancing on the path summarized in this review, already revealing key mechanisms, will continue to be essential contributors to achieve the goals of dampening plaque inflammation and inducing its resolution in order to maximize the therapeutic benefits of conventional risk factor modifications, such as LDL-C lowering.

  13. The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice.

    Science.gov (United States)

    Hoving, Lisa R; de Vries, Margreet R; de Jong, Rob C M; Katiraei, Saeed; Pronk, Amanda; Quax, Paul H A; van Harmelen, Vanessa; Willems van Dijk, Ko

    2018-02-03

    The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden ( E3L ) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

  14. The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

    Directory of Open Access Journals (Sweden)

    Lisa R. Hoving

    2018-02-01

    Full Text Available The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L mice. Male E3L mice were fed a high-cholesterol (1% diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

  15. The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

    OpenAIRE

    Lisa R. Hoving; Margreet R. de Vries; Rob C. M. de Jong; Saeed Katiraei; Amanda Pronk; Paul H. A. Quax; Vanessa van Harmelen; Ko Willems van Dijk

    2018-01-01

    The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce...

  16. Role of parnaparin in atherosclerosis.

    Science.gov (United States)

    Bonomini, Francesca; Taurone, Samanta; Parnigotto, Pierpaolo; Zamai, Loris; Rodella, Luigi F; Artico, Marco; Rezzani, Rita

    2016-12-01

    Atherosclerosis is characterized by a proliferation of vascular smooth muscle cells (VSMCs) and their migration to the intima, which induces thickening of the intima itself, but the mechanism remains poorly understood. Low molecular weight heparin (LMWH) inhibits the proliferation of VSMCs. Previous studies have shown that a LMWH, parnaparin (PNP), acts on the processes of atherogenesis and atheroprogression in experimental animal models. The aim of this study was to investigate the involvement of oxidative stress, inflammation and VSMCs in the regulation of vascular wall homeostasis. We also considered the possibility of restoring vascular pathological changes using PNP treatment. In order to evaluate vascular remodelling in this study we have analysed the morphological changes in aortas of an animal model of atherosclerosis, apolipoprotein E-deficient mice (ApoE-/-) fed with a normal or a western diet without treatment or treated with PNP. We also analysed, by immunohistochemistry, the expression of proteins linked to atherogenesis and atheroprogression - an enzyme involved in oxidative stress, iNOS, examples of inflammatory mediators, such as tumour necrosis factor alpha (TNF-α), interleukins 1 and 6 (IL-1 and IL-6), and markers of VSMC changes, in particular plasminogen activator inhibitor-1 and thrombospondin-1 (PAI-1 and TSP-1). Our results could suggest that PNP downregulates VSMC proliferation and migration, mediated by PAI-1 and TSP-1, and reduces inflammation and oxidative stress in vessels. These data suggested that LMWH, in particular PNP, could be a theoretically practical tool in the prevention of atherosclerotic vascular modification. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

  17. Sphingosine 1-Phosphate and Atherosclerosis

    Science.gov (United States)

    Yatomi, Yutaka

    2018-01-01

    Sphingosine 1-phosphate (S1P) is a potent lipid mediator that works on five kinds of S1P receptors located on the cell membrane. In the circulation, S1P is distributed to HDL, followed by albumin. Since S1P and HDL share several bioactivities, S1P is believed to be responsible for the pleiotropic effects of HDL. Plasma S1P levels are reportedly lower in subjects with coronary artery disease, suggesting that S1P might be deeply involved in the pathogenesis of atherosclerosis. In basic experiments, however, S1P appears to possess both pro-atherosclerotic and anti-atherosclerotic properties; for example, S1P possesses anti-apoptosis, anti-inflammation, and vaso-relaxation properties and maintains the barrier function of endothelial cells, while S1P also promotes the egress and activation of lymphocytes and exhibits pro-thrombotic properties. Recently, the mechanism for the biased distribution of S1P on HDL has been elucidated; apolipoprotein M (apoM) carries S1P on HDL. ApoM is also a modulator of S1P, and the metabolism of apoM-containing lipoproteins largely affects the plasma S1P level. Moreover, apoM modulates the biological properties of S1P. S1P bound to albumin exerts both beneficial and harmful effects in the pathogenesis of atherosclerosis, while S1P bound to apoM strengthens anti-atherosclerotic properties and might weaken the pro-atherosclerotic properties of S1P. Although the detailed mechanisms remain to be elucidated, apoM and S1P might be novel targets for the alleviation of atherosclerotic diseases in the future. PMID:28724841

  18. Stent-assisted angioplasty for intracranial atherosclerosis

    International Nuclear Information System (INIS)

    Nakahara, Toshinori; Sakamoto, Shigeyuki; Hamasaki, Osamu; Sakoda, Katsuaki

    2002-01-01

    We report on two patients with intracranial atherosclerosis of the carotid artery or vertebral artery treated with stent-assisted angioplasty. Both patients have severe intracranial atherosclerosis (>70%) with refractory symptoms despite optimal medical treatment. In both patients, a coronary balloon-expandable stent was successfully placed using a protective balloon technique without procedural complications. The patients were asymptomatic and neurologically intact at a mean clinical follow-up of 13 months. Follow-up angiograms did not show restenosis 3 or 4 months after procedure, respectively. Stent-assisted angioplasty for intracranial atherosclerosis in the elective patient has proven effective, with an acceptable low rate of morbidity and mortality. (orig.)

  19. Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice

    NARCIS (Netherlands)

    Meissner, Maxi; Lombardo, Elisa; Havinga, Rick; Tietge, Uwe J. F.; Kuipers, Folkert; Groen, Albert K.

    2011-01-01

    Objective: Regular physical activity decreases the risk for atherosclerosis but underlying mechanisms are not fully understood. We questioned whether voluntary wheel running provokes specific modulations in cholesterol turnover that translate into a decreased atherosclerotic burden in

  20. Building Integrated Design Practice under the Concept of Sustainable Development

    Science.gov (United States)

    Liu, Xuexin

    2018-03-01

    With the continuous development of social economy, people are more demanding for architecture. Some advanced design concepts are gradually applied to the design of buildings. Under the concept of sustainable development, building integration design has also been widely used to promote the rapid development of architectural design. Integrated design concepts and sustainable development concepts play an important role to meet people’s requirements. This article will explore the concept of sustainable development under the concept of integrated architectural design and practice analysis, propose appropriate measures.

  1. Urban landscape architecture design under the view of sustainable development

    Science.gov (United States)

    Chen, WeiLin

    2017-08-01

    The concept of sustainable development in modern city landscape design advocates landscape architecture, which is the main development direction in the field of landscape design. They are also effective measures to promote the sustainable development of city garden. Based on this, combined with the connotation of sustainable development and sustainable design, this paper analyzes and discusses the design of urban landscape under the concept of sustainable development.

  2. A review of Chlamydia pneumoniae and atherosclerosis

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Fasting, H; Henneberg, E W

    1999-01-01

    Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that causes acute upper and lower respiratory infections. Its distribution is worldwide. Seroepidemiological studies have shown an association between C. pneumoniae and atherosclerosis, and the risk of acute myocardial...

  3. Gender-Related Differences in Atherosclerosis

    Czech Academy of Sciences Publication Activity Database

    Mathur, P.; Ošťádal, Bohuslav; Romeo, F.; Mehta, J. L.

    2015-01-01

    Roč. 29, č. 4 (2015), s. 319-327 ISSN 0920-3206 Institutional support: RVO:67985823 Keywords : atherosclerosis * gender Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.189, year: 2015

  4. Increased Cardiovascular Events and Subclinical Atherosclerosis in Rheumatoid Arthritis Patients: 1 Year Prospective Single Centre Study.

    Directory of Open Access Journals (Sweden)

    Piero Ruscitti

    Full Text Available Several studies showed the close relationship between Rheumatoid Arthritis (RA and cerebro-cardiovascular events (CVEs and subclinical atherosclerosis. In this study, we investigated the occurrence of CVEs and subclinical atherosclerosis during the course of RA and we evaluated the possible role of both traditional cardiovascular (CV and disease related risk factors to predict the occurrence of new CVEs and the onset of subclinical atherosclerosis.We designed a single centre, bias-adjusted, prospective, observational study to investigate, in a homogeneous subset of RA patients, the occurrence of new onset of CVEs and subclinical atherosclerosis. Statistical analyses were performed to evaluate the role of traditional CV and disease-related risk factors to predict the occurrence of new CVEs and subclinical atherosclerosis.We enrolled 347 RA patients prospectively followed for 12 months. An increased percentage of patients experienced CVEs, developed subclinical atherosclerosis and was affected by systemic arterial hypertension (SAH, type 2 diabetes mellitus and metabolic syndrome (MS, at the end of follow up. Our analysis showed that the insurgence of both SAH and MS, during the follow up, the older age, the CVE familiarity and the lack of clinical response, were associated with a significantly increased risk to experience CVEs and to develop subclinical atherosclerosis.Our study quantifies the increased expected risk for CVEs in a cohort of RA patients prospectively followed for 1 year. The occurrence of both new CVEs and subclinical atherosclerosis in RA patients may be explained by inflammatory burden as well as traditional CV risk factors.

  5. Atherosclerosis-Associated Endothelial Cell Apoptosis by MiR-429-Mediated Down Regulation of Bcl-2

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2015-10-01

    Full Text Available Background/Aims: Endothelial cell injury and subsequent apoptosis play a key role in the development and pathogenesis of atherosclerosis, which is hallmarked by dysregulated lipid homeostasis, aberrant immunity and inflammation, and plaque-instability-associated coronary occlusion. Nevertheless, our understanding of the mechanisms underlying endothelial cell apoptosis is still limited. MicroRNA-429 (miR-29 is a known cancer suppressor that promotes cancer cell apoptosis. However, it is unknown whether miR-429 may be involved in the development of atherosclerosis through similar mechanisms. We addressed these questions in the current study. Methods: We examined the levels of endothelial cell apoptosis in ApoE (-/- mice suppled with high-fat diet (HFD, a mouse model for atherosclerosis (simplified as HFD mice. We analyzed the levels of anti-apoptotic protein Bcl-2 and the levels of miR-429 in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-429 and 3'-UTR of Bcl-2 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-429 were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL-treated human aortic endothelial cells (HAECs. Results: HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/- mice that had received normal diet (simplified as NOR mice did not. HFD mice had significantly lower percentage of endothelial cells and significantly higher percentage of mesenchymal cells in the aorta than NOR mice. Significantly higher levels of endothelial cell apoptosis were detected in HFD mice, resulting from decreases in Bcl-2 protein, but not mRNA. The decreases in Bcl-2 in endothelial cells were due to increased levels of miR-429, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Conclusion: Atherosclerosis

  6. [Chronic mild inflammation links obesity, metabolic syndrome, atherosclerosis and diabetes].

    Science.gov (United States)

    Andel, M; Polák, J; Kraml, P; Dlouhý, P; Stich, V

    2009-01-01

    Chronic low grade inflammation is relatively new concept in metabolic medicine. This concept describes the relations between the inflammation and adipose tissue, insulin resistence, atherosclerosis and type 2 diabetes mellitus. Macrophages and lymphocytes deposed in adipose tissue produce proinflammatory cytokines which directly or through the CRP liver secretion are targeting endothelial cells, hepatocytes and beta cells of Langerhans islets of pancreas. The dysfunction of these cells follows often further disturbances and in case of beta cells - the cell death. The connection between the adipose tissue insulin resistence, atherosclerosis and type 2 diabetes was earlier described with endocrine and metabolic descriptors. The concept of chronic low grade inflammation creates also another description of multilateral connections in metabolic syndome. The salicylates and the drugs related to them seem to have some glucose lowering properties. The recent development in the field ofchronic low grade inflammation represents also certain therapeutic hope for antiinflammatory intervention in type 2 diabetes.

  7. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    International Nuclear Information System (INIS)

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-01-01

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

  8. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-10

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

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

    Science.gov (United States)

    Thompson, D; Morrice, N; Grant, L; Le Sommer, S; Ziegler, K; Whitfield, P; Mody, N; Wilson, H M; Delibegović, M

    2017-08-01

    Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with Type 1 or Type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance due to impaired insulin receptor (IR) signaling. Moreover, inflammatory cells, in particular macrophages, play a key role in pathogenesis of atherosclerosis and insulin resistance in humans. We hypothesized that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR, specifically in macrophages, would have beneficial anti-inflammatory effects and lead to protection against atherosclerosis and CVD. We generated novel macrophage-specific PTP1B knockout mice on atherogenic background (ApoE -/- /LysM-PTP1B). Mice were fed standard or pro-atherogenic diet, and body weight, adiposity (echoMRI), glucose homeostasis, atherosclerotic plaque development, and molecular, biochemical and targeted lipidomic eicosanoid analyses were performed. Myeloid-PTP1B knockout mice on atherogenic background (ApoE -/- /LysM-PTP1B) exhibited a striking improvement in glucose homeostasis, decreased circulating lipids and decreased atherosclerotic plaque lesions, in the absence of body weight/adiposity differences. This was associated with enhanced phosphorylation of aortic Akt, AMPKα and increased secretion of circulating anti-inflammatory cytokine interleukin-10 (IL-10) and prostaglandin E2 (PGE 2 ), without measurable alterations in IR phosphorylation, suggesting a direct beneficial effect of myeloid-PTP1B targeting. Here we demonstrate that inhibiting the activity of PTP1B specifically in myeloid lineage cells protects against atherosclerotic plaque formation, under atherogenic conditions, in an ApoE -/- mouse model of atherosclerosis. Our findings suggest for the first time that macrophage PTP1B targeting could be a therapeutic target for atherosclerosis treatment and reduction of CVD risk.

  10. Aterosclerose experimental em coelhos Experimental atherosclerosis in rabbits

    Directory of Open Access Journals (Sweden)

    Waleska C. Dornas

    2010-08-01

    Full Text Available Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes quantidades no plasma, a utilização destes animais como modelo experimental para avaliar o desenvolvimento de aterosclerose é de grande relevância, trazendo informação sobre fatores que contribuem para progressão e regressão aplicadas a situações humanas. Sendo assim, nessa revisão a função aterogênica do colesterol é mostrada em trabalhos que incluem o coelho como modelo experimental, uma vez que este animal tornou-se o mais popular modelo experimental de aterosclerose.Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.

  11. FY 1995 basic research to develop instruments for diagnosis of atherosclerosis on the basis of autofluorescence analysis of blood and vascular walls; 1995 nendo ketsueki oyobi kekkanheki no jiko keiko bunseki ni yoru domyaku koka shindan kiki kaiahtsu no tame no kisoteki kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    To obtain the basic data to develop instruments for diagnosis of atherosclerosis and to elucidate the mechanisms of atherogenesis by focusing on the autofluorescence of blood and vascular walls of atherosclerotic animal models and human patients. We have performed experiments to examine the relationships between autofluorescence of blood and vascular walls of guinea pig atherosclerotic model and human patients and obtained the following results. 1. The autofluorescence from human atherosclerotic aorta included the components with longer wave length than normal aorta, suggesting that diagnosis of atherosclerotic aortic walls will be possible using spectroscopic analysis through glass fiber catheter into vascular system. Further studies should be needed to the quantitative diagnosis. 2. The autofluorescence from blood plasma of human atherosclerotic patients has showed that the peak wave length was shorter than that of normal plasma. This phenomenon was mainly caused by the oxidization of plasma, especially lipoproteins, LDL and HDL. 3. Atherosclerotic model of the guinea pigs was quite similar to human atherosclerosis at the points of cholesterol levels and localization of lipid deposit to arterial walls, and showed to be useful for the studies of atherosclerosis. (NEDO)

  12. Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects.

    Science.gov (United States)

    Zheng, Bin; Yang, Liu; Wen, Caixia; Huang, Xiuwang; Xu, Chenxia; Lee, Kuan-Han; Xu, Jianhua

    2016-03-15

    L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Protective role for properdin in progression of experimental murine atherosclerosis.

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    Tanja Steiner

    Full Text Available Genetic, dietary and immune factors contribute to the pathogenesis of atherosclerosis in humans and mice. Complement activation is an integral part of the innate immune defence but also shapes cellular responses and influences directly triglyceride synthesis. Deficiency of Factor B of the alternative pathway (AP of complement is beneficial in LDLR(-/- mice fed a high fat diet. The serum glycoprotein properdin is a key positive regulator of the AP but has not been studied in experimental atherosclerosis. Atherosclerosis was assessed after feeding low fat (LFD or high fat (HFD Western type diets to newly generated LDLR(-/- Properdin(KO (LDLR(-/-P(KO and LDLR-/-PWT mice. Lipids, lymphocytes and monocytes were similar among genotypes, genders and diets. Complement C3, but not C3adesarg, levels were enhanced in LDLR(-/-P(KO mice regardless of diet type or gender. Non-esterified fatty acids (NEFA were decreased in male LDLR(-/-P(KO fed a HFD compared with controls. All mice showed significant atherosclerotic burden in aortae and at aortic roots but male LDLR(-/- mice fed a LFD were affected to the greatest extent by the absence of properdin. The protective effect of properdin expression was overwhelmed in both genders of LDLR(-/-mice when fed a HFD. We conclude that properdin plays an unexpectedly beneficial role in the development and progression of early atherosclerotic lesions.

  14. Food and nutrition in the prevention of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Izabela Kamila Wojarska

    2018-05-01

    Full Text Available Cardiovascular disease is the most frequent cause of hospitalization (15% and death (46% in Poland, as well as worldwide (31%, by reason of strenuous activity in the field of preventative healthcare in all age groups has to be taken. Preventative nutrition of atherosclerosis predicts mostly intake restriction of food containing: fatty acids, cholesterol, salt, monosaccharides and animal protein, while increasing intake of vitamins, minerals, fiber and antioxidant substances. Eating habits and nutritional status of women who are planning pregnancy have a crucial impact on its course, development of the fetus and children’s health in later years of their life. For all of cardiac patients well balanced diet is advised. In preventative care of Cardiovascular Disease it is advised to apply the diet given by a certified dietician and adjusted to fit patient’s needs. It is to remember, that besides a good diet, an important therapeutic factor of the patients with atherosclerosis is physical activity. Cardiovascular disease is a serious concern in Poland, as well as worldwide. Eating habits are playing a big role in pathogenesis and prevention of atherosclerosis.

  15. Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

    Science.gov (United States)

    Das, S; Ray, R; Snehlata; Das, N; Srivastava, L M

    2006-04-01

    The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

  16. Follicular B Cells Promote Atherosclerosis via T Cell-Mediated Differentiation Into Plasma Cells and Secreting Pathogenic Immunoglobulin G.

    Science.gov (United States)

    Tay, Christopher; Liu, Yu-Han; Kanellakis, Peter; Kallies, Axel; Li, Yi; Cao, Anh; Hosseini, Hamid; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

    2018-05-01

    B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster of differentiation 40), and Blimp-1 (B-lymphocyte-induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. Using mixed chimeric Ldlr -/- mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells. During development of atherosclerosis, these deficiencies affected T-B cell interactions, germinal center B cells, plasma cells, and IgG. As FO B cells differentiating into plasma cells require Blimp-1, we also assessed its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly attenuated atherosclerosis and immunoglobulin-including IgG production, preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic core. To determine the importance of IgG for atherosclerosis, we purified IgG from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic mice into Ldlr -/- mice whose B cells are Blimp-1-deficient increased atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and necrotic core size. The mechanism by which FO B cells promote atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp-1. FO B cell differentiation into IgG-producing plasma cells also is critical for their proatherogenic actions. Targeting B-T cell interactions and pathogenic IgG may provide novel therapeutic strategies to prevent atherosclerosis and its adverse cardiovascular complications. © 2018 American Heart Association, Inc.

  17. Research on the Food Green Packaging Under the Sustainable Development

    OpenAIRE

    Wang Qiang; Zhou Min

    2015-01-01

    With the rapid growth in economy and the constant development in people living standard, packaging has become an indispensable part to human activities. However, the ways and materials popular used for packaging currently have been making a great deal of recourse waste and serious pollution to the environments. From the existing problems in food packaging, the study has put forward the necessity of green packaging under the idea of sustainable development and discussed the approach of green f...

  18. Carotid Atherosclerosis and Cognitive Impairment in Nonstroke Patients

    Directory of Open Access Journals (Sweden)

    Wei-Hong Chen

    2017-01-01

    Conclusions: Carotid atherosclerosis can be used to predict the risk of cognitive impairment. Furthermore, diagnosing and treating carotid atherosclerosis at early stage might help clinicians prevent and treat vascular cognitive impairment in nonstroke patients.

  19. Poverty and Under-Development in Nigeria | Aghayere | Lwati: A ...

    African Journals Online (AJOL)

    This paper looks at poverty and under-development in the Olusegun Obasanjo first democratic years in Nigeria. It sees poverty as a condition where an individual or organization experiences a situation of lack, a situation with little or no resource to acquire the basic necessities of life. It goes further to look at the concept of ...

  20. Relationship between Chlamydia pneumonia and helicobacter pylori with atherosclerosis

    Directory of Open Access Journals (Sweden)

    ali Pooria

    2009-01-01

    Full Text Available Pooria A1, Maasoomi M2, Rafiee E3, Rezaee M4, Sabzi F5, Hossain Zadegan H6, Salehi M7, Mozaffari P8 1. Assistant Professor, Department of Surgery, Faculty of Medicine, Lorestan University of Medical Sciences 2. Professor, Department of Surgery, Faculty of Medicine, Kermanshah University of Medical Sciences, 3. Assistant Professor, Faculty of Medicine, Lorestan University of Medical Sciences, Department of Pathology 4. Associate Professor, Department of Surgery, Faculty of Medicine, Kermanshah University of Medical Sciences 5. Assistant Professor, Department of Statistics, Faculty of Health, Kermanshah University of Medical Sciences 6. Assistant Professor, Department of Microbiology, Faculty of Medicine, Lorestan University of Medical Sciences 7. Bsc in Nursing, Kermanshah University of Medical Sciences 8. Instructor, Department of Nursing, Faculty of Nursing and midwifery, Kermanshah University of Medical Sciences Abstract Background: Atherosclerosis is the most common cause of deaths in the developed countries and causes one million mortalities per year in the USA. Smoking, hypertension, diabetes, obesity, hyperlipidemia, stress, and low activity are known to be the causes of atherosclerosis. The objective of this study is to confirm the relationship between chlamydia pneumonia (Cpn, as well as helicobacter pylori (Hp and atherosclerosis. Materials and methods: In this analytical case-control study two groups of patients were studied. The first group including 30 patients over 30 years old with coronary artery disease were operated using coronary artery bypass graft. The control group included 30 persons assessed with angiography and having normal coronary arteries. The data were collected and analyzed using statistical methods. Results: The two groups were similar in terms of IgA and IgG anti-Cpn, and IgG anti- Hp but they were statistically different concerning IgA anti-Hp which had more positive cases in the case group in comparison with the

  1. Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

    Science.gov (United States)

    Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

    2014-01-01

    The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

  2. Risk of carotid atherosclerosis associated with genetic polymorphisms of apolipoprotein E and inflammatory genes among arsenic exposed residents in Taiwan

    International Nuclear Information System (INIS)

    Hsieh, Y.-C.; Hsieh, F.-I; Lien, L.-M.; Chou, Y.-L.; Chiou, H.-Y.; Chen, C.-J.

    2008-01-01

    Arsenic had been reported to be associated with carotid atherosclerosis. However, there were few studies to evaluate the association between the susceptible gene of lipid metabolism and inflammation and carotid atherosclerosis among arsenic exposure residents. The aim of the study was to investigate the associations between the genetic polymorphisms of APOE and MCP-1 and the risk of carotid atherosclerosis among residents of Lanyang Basin in Taiwan which was a newly confirmed arsenic-endemic area. In total, 479 residents who had been genotyped of these two genes and examined the severity of carotid atherosclerosis were included in this study. The study subjects with carotid intima media thickness (IMT) ≥ 1.0 mm or with the observable plaque in the extracranial carotid artery were diagnosed as carotid atherosclerosis. A significantly age- and gender-adjusted odds ratio of 2.0 for the development of carotid atherosclerosis was observed in study subjects with ε4 allele of APOE than those without ε4 allele. Compared with study subjects who carried wild genotypes of APOE and MCP-1, those with both risk genotypes of APOE and MCP-1 had 2.5-fold risk of carotid atherosclerosis after adjustment for age and gender, revealing a significant dose-response relationship between number of risk genotypes of these genes and risk of carotid atherosclerosis. Additionally, study subjects with two risk genotypes of APOE and MCP-1 and either had ingested well water contained arsenic level > 10 μg/L or had arsenic exposure > 0.22 mg/L-year would have strikingly highest risk of 10.3-fold and 15.7-fold, respectively, for the development carotid atherosclerosis, showing significant joint effect of arsenic exposure and risk genotypes of APOE and MCP-1

  3. The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA: rationale and design

    Directory of Open Access Journals (Sweden)

    Pera Guillem

    2011-02-01

    Full Text Available Abstract Background Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA study are (1 to determine the prevalence of ASIA in a moderate-high vascular risk population, (2 to study its prognostic impact on the risk of suffering future major ischemic events, and (3 to identify predictors of the development, progression and clinical expression of this condition. Methods/Design Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5% and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA. Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. Discussion The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better

  4. The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA): rationale and design.

    Science.gov (United States)

    López-Cancio, Elena; Dorado, Laura; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Massuet, Anna; Mataró, María; Galán, Amparo; Alzamora, Maite; Pera, Guillem; Torán, Pere; Dávalos, Antoni; Arenillas, Juan F

    2011-02-17

    Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from

  5. Factors associated with accelerated subclinical atherosclerosis in patients with spondyloarthritis without overt cardiovascular disease.

    Science.gov (United States)

    Giollo, Alessandro; Dalbeni, Andrea; Cioffi, Giovanni; Ognibeni, Federica; Gatti, Davide; Idolazzi, Luca; Orsolini, Giovanni; Minuz, Pietro; Rossini, Maurizio; Fava, Cristiano; Viapiana, Ombretta

    2017-11-01

    Data on the progression of atherosclerosis in spondyloarthritis (SpA) are scarce, despite a high burden of cardiovascular diseases (CVD). The aim of this study was to identify the predictors of an accelerated subclinical atherosclerosis in patients with SpA. Study participants were 66 patients free of CVD classified according to ASAS criteria. The patients were evaluated at baseline and after 13.5 ± 3.6 months. Ultrasound measurements of carotid intima-media thickness (cIMT) and distensibility coefficient (cDC) were used to assess the extent of subclinical atherosclerosis. cIMT progression rate was calculated dividing the cIMT change by the time between the scans. Accelerated atherosclerosis was defined as the top cIMT progression rate quartile. At baseline, the mean Framingham Risk Score was 14 ± 11%. At follow-up, cIMT increased in 39 patients (59%; mean difference 0.01 ± 0.10; p = 0.334). Mean cIMT progression rate was 0.01 mm/year (95% CI - 0.02 to 0.03). cDC was unchanged at follow-up. Patients with accelerated atherosclerosis (n = 16) had significantly higher serum creatinine and lower glomerular filtration rate (eGFR) at baseline. In multiple logistic regression, only eGFR and the presence of syndesmophytes were associated with an accelerated atherosclerosis, independent of traditional cardiovascular risk factors. In patients with SpA without overt CV disease, a decrease in renal function and radiographic damage are conditions associated with the development of subclinical accelerated atherosclerosis. Longitudinal assessment of cIMT could be useful to better evaluate the individual CV risk of these patients improving their prognostic stratification.

  6. Open Source Power Plant Simulator Development Under Matlab Environment

    International Nuclear Information System (INIS)

    Ratemi, W.M.; Fadilah, S.M.; Abonoor, N

    2008-01-01

    In this paper an open source programming approach is targeted for the development of power plant simulator under Matlab environment. With this approach many individuals can contribute to the development of the simulator by developing different orders of complexities of the power plant components. Such modules can be modeled based on physical principles, or using neural networks or other methods. All of these modules are categorized in Matlab library, of which the user can select and build up his simulator. Many international companies developed its own authoring tool for the development of its simulators, and hence it became its own property available for high costs. Matlab is a general software developed by mathworks that can be used with its toolkits as the authoring tool for the development of components by different individuals, and through the appropriate coordination, different plant simulators, nuclear, traditional , or even research reactors can be computerly assembled. In this paper, power plant components such as a pressurizer, a reactor, a steam generator, a turbine, a condenser, a feedwater heater, a valve, a pump are modeled based on physical principles. Also a prototype modeling of a reactor ( a scram case) based on neural networks is developed. These modules are inserted in two different Matlab libraries one called physical and the other is called neural. Furthermore, during the simulation one can pause and shuffle the modules selected from the two libraries and then proceed the simulation. Also, under the Matlab environment a PID controller is developed for multi-loop plant which can be integrated for the control of the appropriate developed simulator. This paper is an attempt to base the open source approach for the development of power plant simulators or even research reactor simulators. It then requires the coordination among interested individuals or institutions to set it to professionalism. (author)

  7. Transcriptional profiling uncovers a network of cholesterol-responsive atherosclerosis target genes.

    Directory of Open Access Journals (Sweden)

    Josefin Skogsberg

    2008-03-01

    Full Text Available Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr(-/-Apo(100/100Mttp(flox/flox Mx1-Cre. Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies.

  8. [Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

    Science.gov (United States)

    Machalińska, Anna

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

  9. Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids.

    Science.gov (United States)

    Trenteseaux, Charlotte; Gaston, Anh-Thu; Aguesse, Audrey; Poupeau, Guillaume; de Coppet, Pierre; Andriantsitohaina, Ramaroson; Laschet, Jamila; Amarger, Valérie; Krempf, Michel; Nobecourt-Dupuy, Estelle; Ouguerram, Khadija

    2017-11-01

    Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and

  10. Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

    Directory of Open Access Journals (Sweden)

    Héctor Rincón-Arévalo

    2016-06-01

    Full Text Available Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/− mice fed or not with high-fat diet (HFD, by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410 [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia.

  11. Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

    Science.gov (United States)

    Rincón-Arévalo, Héctor; Castaño, Diana; Villa-Pulgarín, Janny; Rojas, Mauricio; Vásquez, Gloria; Correa, Luis A.; Ramírez-Pineda, José R.; Yassin, Lina M.

    2016-01-01

    Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/−) mice fed or not with high-fat diet (HFD), by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410) [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia. PMID:27081674

  12. Developments in Undernutrition in Indian Children Under Five

    DEFF Research Database (Denmark)

    Nie, Peng; Rammohan, Anu; Gwozdz, Wencke

    This study uses two waves (2004-2005 and 2011-2012) of the nationally representative Indian Human Development Survey to conduct a systematic decompositional analysis of the demographic and socio-economic factors contributing to undernutrition among children under five in India. The analytic method...... improvements on some measures, undernutrition among India's young children remains widespread. The improvements we do identify are partly attributable to changes in household wealth and maternal characteristics like body mass index and education....

  13. Inherited disorders of HDL metabolism and atherosclerosis

    NARCIS (Netherlands)

    Hovingh, G Kees; de Groot, E.P.; van der Steeg, Wim; Boekholdt, S Matthijs; Hutten, Barbara A; Kuivenhoven, J.A.; Kastelein, John J P

    PURPOSE OF REVIEW: Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

  14. Inherited disorders of HDL metabolism and atherosclerosis

    NARCIS (Netherlands)

    Hovingh, G. Kees; de Groot, Eric; van der Steeg, Wim; Boekholdt, S. Matthijs; Hutten, Barbara A.; Kuivenhoven, Jan Albert; Kastelein, John J. P.

    2005-01-01

    Purpose of review Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

  15. Metabonomics-based omics study and atherosclerosis

    OpenAIRE

    Wu, Duo-jiao; Zhu, Bi-jun; Wang, Xiang-dong

    2011-01-01

    Atherosclerosis results from dyslipidemia and systemic inflammation, associated with the strong metabolism and interaction between diet and disease. Strategies based on the global profiling of metabolism would be important to define the mechanisms involved in pathological alterations. Metabonomics is the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. Metabonomics has been used in combination w...

  16. Neutrophils in atherosclerosis. A brief overview

    NARCIS (Netherlands)

    Hartwig, H.; Silvestre Roig, C.; Daemen, M.; Lutgens, E.; Soehnlein, O.

    2015-01-01

    Atherosclerosis is a chronic inflammation of the arterial wall and the continuous infiltration of leukocytes into the plaque enhances the progression of the lesion. Because of the scarce detection of neutrophils in atherosclerotic plaques compared to other immune cells, their contribution was

  17. Effects of apolipoprotein M in uremic atherosclerosis

    DEFF Research Database (Denmark)

    Bosteen, Markus Høybye; Madsen Svarrer, Eva Martha; Bisgaard, Line Stattau

    2017-01-01

    BACKGROUND AND AIMS: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute...

  18. Cyanotic congenital heart disease and atherosclerosis

    DEFF Research Database (Denmark)

    Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas

    2017-01-01

    Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether...

  19. Overview of Atherosclerosis and Chemical Stressors

    Science.gov (United States)

    Dr. Cascio’s presentation at the workshop titled, “titled “Understanding the Combined Effects of Environmental Chemical and Non-Chemical Stressors: Atherosclerosis as a Model” will highlight atherosclerosis’s rapidly growing role as a cause of increa...

  20. Anti-inflammatory and anti-thrombotic intervention strategies using atorvastatin, clopidogrel and knock-down of CD40L do not modify radiation-induced atherosclerosis in ApoE null mice

    Energy Technology Data Exchange (ETDEWEB)

    Hoving, Saske [Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Heeneman, Sylvia [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Gijbels, Marion J.J. [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (Netherlands); Poele, Johannes A.M. te [Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Pol, Jeffrey F.C.; Gabriels, Karen [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Russell, Nicola S [Division of Radiotherapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Daemen, Mat J.A.P. [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Department of Pathology, AMC, Amsterdam (Netherlands); Stewart, Fiona A., E-mail: f.stewart@nki.nl [Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands)

    2011-10-15

    Background and purpose: We previously showed that irradiating the carotid arteries of ApoE{sup -/-} mice accelerated the development of macrophage-rich, inflammatory and thrombotic atherosclerotic lesions. In this study we investigated the potential of anti-inflammatory (atorvastatin, CD40L knockout) and anti-thrombotic (clopidogrel) intervention strategies to inhibit radiation-induced atherosclerosis. Material and methods: ApoE{sup -/-} mice were given 0 or 14 Gy to the neck and the carotid arteries were harvested at 4 or 28 weeks after irradiation. Atorvastatin (15 mg/kg/day) or clopidogrel (20 mg/kg/day) was given in the chow; control groups received regular chow. Clopidogrel inhibited platelet aggregation by 50%. CD40L{sup -/-}/ApoE{sup -/-} and ApoE{sup -/-} littermates were also given 0 or 14 Gy to the neck and the carotid arteries were harvested after 30 weeks. Results: Clopidogrel decreased MCP-1 expression in the carotid artery at 4 weeks after irradiation. Expression of VCAM-1, ICAM-1, thrombomodulin, tissue factor and eNOS was unchanged in atorvastatin and clopidogrel-treated mice. Neither drug inhibited either age-related or radiation-induced atherosclerosis. Furthermore, loss of the inflammatory mediator CD40L did not influence the development of age-related and radiation-induced atherosclerosis. Conclusions: The effects of radiation-induced atherosclerosis could not be circumvented by these specific anti-inflammatory and anti-coagulant therapies. This suggests that more effective drug combinations may be required to overcome the radiation stimulus, or that other underlying mechanistic pathways are involved compared to age-related atherosclerosis.

  1. Anti-inflammatory and anti-thrombotic intervention strategies using atorvastatin, clopidogrel and knock-down of CD40L do not modify radiation-induced atherosclerosis in ApoE null mice

    International Nuclear Information System (INIS)

    Hoving, Saske; Heeneman, Sylvia; Gijbels, Marion J.J.; Poele, Johannes A.M. te; Pol, Jeffrey F.C.; Gabriels, Karen; Russell, Nicola S.; Daemen, Mat J.A.P.; Stewart, Fiona A.

    2011-01-01

    Background and purpose: We previously showed that irradiating the carotid arteries of ApoE −/− mice accelerated the development of macrophage-rich, inflammatory and thrombotic atherosclerotic lesions. In this study we investigated the potential of anti-inflammatory (atorvastatin, CD40L knockout) and anti-thrombotic (clopidogrel) intervention strategies to inhibit radiation-induced atherosclerosis. Material and methods: ApoE −/− mice were given 0 or 14 Gy to the neck and the carotid arteries were harvested at 4 or 28 weeks after irradiation. Atorvastatin (15 mg/kg/day) or clopidogrel (20 mg/kg/day) was given in the chow; control groups received regular chow. Clopidogrel inhibited platelet aggregation by 50%. CD40L −/− /ApoE −/− and ApoE −/− littermates were also given 0 or 14 Gy to the neck and the carotid arteries were harvested after 30 weeks. Results: Clopidogrel decreased MCP-1 expression in the carotid artery at 4 weeks after irradiation. Expression of VCAM-1, ICAM-1, thrombomodulin, tissue factor and eNOS was unchanged in atorvastatin and clopidogrel-treated mice. Neither drug inhibited either age-related or radiation-induced atherosclerosis. Furthermore, loss of the inflammatory mediator CD40L did not influence the development of age-related and radiation-induced atherosclerosis. Conclusions: The effects of radiation-induced atherosclerosis could not be circumvented by these specific anti-inflammatory and anti-coagulant therapies. This suggests that more effective drug combinations may be required to overcome the radiation stimulus, or that other underlying mechanistic pathways are involved compared to age-related atherosclerosis.

  2. Supply chain management under fuzziness recent developments and techniques

    CERN Document Server

    Öztayşi, Başar

    2014-01-01

    Supply Chain Management Under Fuzziness presents recently developed fuzzy models and techniques for supply chain management. These include: fuzzy PROMETHEE, fuzzy AHP, fuzzy ANP, fuzzy VIKOR, fuzzy DEMATEL, fuzzy clustering, fuzzy linear programming, and fuzzy inference systems. The book covers both practical applications and new developments concerning these methods. This book offers an excellent resource for researchers and practitioners in supply chain management and logistics, and will provide them with new suggestions and directions for future research. Moreover, it will support graduate students in their university courses, such as specialized courses on supply chains and logistics, as well as related courses in the fields of industrial engineering, engineering management and business administration.

  3. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  4. Gender-Specific Association of Desacylated Ghrelin with Subclinical Atherosclerosis in the Metabolic Syndrome.

    Science.gov (United States)

    Zanetti, Michela; Gortan Cappellari, Gianluca; Semolic, Annamaria; Burekovic, Ismet; Fonda, Maurizio; Cattin, Luigi; Barazzoni, Rocco

    2017-07-01

    Ghrelin, a gastric hormone with pleiotropic effects modulates vascular function and may influence atherosclerosis. Plasma ghrelin is reduced in the metabolic syndrome (MS), which is also characterized by early atherosclerosis. Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative impact and that of gender on subclinical atherosclerosis in MS is unknown. To investigate potential associations of total, AG and DAG with carotid atherosclerosis and with gender in the MS. Plasma total ghrelin, AG, DAG and carotid artery IMT (cIMT) were measured in 46 MS patients (NCEP-ATP III criteria, 22M/24F). Compared with males, females had higher (p ghrelin nor AG and DAG were associated with cIMT in all MS patients nor in the male subgroup. In females, a negative (p ghrelin and AG. In multivariate modeling, DAG remained negatively (p <0.05) associated with cIMT after adjusting for plasma glucose and cardiovascular risk factors. These data indicate a negative independent association between DAG and cIMT in middle-aged women with the MS and suggest a gender-specific modulatory function of DAG in the development of atherosclerosis. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  5. [The impact of electronic cigarettes usage on the endothelial function and the progression of atherosclerosis].

    Science.gov (United States)

    Knura, Miłosz; Dragon, Jonasz; Łabuzek, Krzysztof; Okopień, Bogusław

    2018-01-23

    The exponetial growth in popularity of electronic cigarettes in the world markets intensifies the debate about their health effects. The smoking of traditional tabacoo products is a factor associated with the endothelium damage and progression of atherosclerosis. The elimination of the combustion process in electronic cigarettes allows to conclude that they are less harmful to a vascular endothelium than traditional tobacco products. E-cigarette aerosol contains many compounds that have an influence on initiation and progression of atherosclerosis. Nicotine protherogenic action is not fully explained. On one hand, nicotine modifies metabolic pathways leading to atherosclerosis, whereas epidemiological studies do not show an increased risk of cardiovascular disease in the population using nicotine replacement therapy or snuff. Acrolein, formaldehyde and the ultrafine particles generated during e-liquid heating have an impact on initiation and progression of atherosclerosis, but their level is lower than that of tobacco smoke. In order to assess accurately the longterm effects of e-cigarettes, it is necessary to conduct epidemiological studies measuring the effects of using e-cigarettes. It is claimed that the use of electronic cigarettes has a potential impact on the development of atherosclerosis, but is significantly lower than that of traditional cigarettes.

  6. Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

    Science.gov (United States)

    Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

    2013-01-01

    The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

  7. The Multifaceted Uses and Therapeutic Advantages of Nanoparticles for Atherosclerosis Research.

    Science.gov (United States)

    DiStasio, Nicholas; Lehoux, Stephanie; Khademhosseini, Ali; Tabrizian, Maryam

    2018-05-08

    Nanoparticles are uniquely suited for the study and development of potential therapies against atherosclerosis by virtue of their size, fine-tunable properties, and ability to incorporate therapies and/or imaging modalities. Furthermore, nanoparticles can be specifically targeted to the atherosclerotic plaque, evading off-target effects and/or associated cytotoxicity. There has been a wealth of knowledge available concerning the use of nanotechnologies in cardiovascular disease and atherosclerosis, in particular in animal models, but with a major focus on imaging agents. In fact, roughly 60% of articles from an initial search for this review included examples of imaging applications of nanoparticles. Thus, this review focuses on experimental therapy interventions applied to and observed in animal models. Particular emphasis is placed on how nanoparticle materials and properties allow researchers to learn a great deal about atherosclerosis. The objective of this review was to provide an update for nanoparticle use in imaging and drug delivery studies and to illustrate how nanoparticles can be used for sensing and modelling, for studying fundamental biological mechanisms, and for the delivery of biotherapeutics such as proteins, peptides, nucleic acids, and even cells all with the goal of attenuating atherosclerosis. Furthermore, the various atherosclerosis processes targeted mainly for imaging studies have been summarized in the hopes of inspiring new and exciting targeted therapeutic and/or imaging strategies.

  8. Effect of tocotrienol on aortic atherosclerosis in diabetic mice

    International Nuclear Information System (INIS)

    Kiani, M.R.B.; Butt, S.A.; Ahmed, T.

    2015-01-01

    Effect of tocotrienol on aortic atherosclerosis in diabetic mice To study the histomorphological effect of tocotrienol on aortic atherosclerosis in diabetic mice having high fat diet. Study Design: Lab based randomized controlled trial. Place and Duration of Study: Army Medical College, Rawalpindi and National Institute of Health, Islamabad from November 2009 to June 2010. Material and Methods: Forty five female BALB/c mice were randomly divided into three groups. The diabetic mice model was established by intraperitoneal injection of streptozotocin (STZ) 40 mg/kg body weight. Group A was given normal laboratory diet, group B high fat diet and group C was given tocotrienol along with high fat diet for 32 weeks. At the end of experiment the mice were sacrificed. The hearts of animals were dissected out and ascending aortae were taken out. The specimen was fixed in 10% formol calcium and processed for paraffin embedding. Five micrometer thick sections were made for haematoxylin and eosin, and Verhoeff's staining. After staining, histomorphologic changes in slides were noted. Results: In contrast to group A, atheroscelrosis developed in groups B and C. Statistically significant atherosclerotic changes were found in the aortae of diabetic mice in group B when compared to group A. On comparison of group A to C, atherosclerotic changes were statistically insignificant. However when group B was compared with group C, the aortic atherosclerotic changes decreased significantly in group C. Conclusion: In diabetics with high fat diet intake, there is an increase in development of atherosclerosis in aorta which can be reduced by tocotrienol. (author)

  9. Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties

    OpenAIRE

    Sendobry, Sandra M; Cornicelli, Joseph A; Welch, Kathryn; Bocan, Thomas; Tait, Bradley; Trivedi, Bharat K; Colbry, Norman; Dyer, Richard D; Feinmark, Steven J; Daugherty, Alan

    1997-01-01

    15-Lipoxygenase (15-LO) has been implicated in the pathogenesis of atherosclerosis because of its localization in lesions and the many biological activities exhibited by its products. To provide further evidence for a role of 15-LO, the effects of PD 146176 on the development of atherosclerosis in cholesterol-fed rabbits were assessed. This novel drug is a specific inhibitor of the enzyme in vitro and lacks significant non specific antioxidant properties.PD 146176 inhibited rabbit reticulocyt...

  10. Roles and Mechanisms of Obstructive Sleep Apnea-Hypopnea Syndrome and Chronic Intermittent Hypoxia in Atherosclerosis: Evidence and Prospective.

    Science.gov (United States)

    Ma, Linqin; Zhang, Jingchun; Liu, Yue

    2016-01-01

    The morbidity and mortality of obstructive sleep apnea-hypopnea syndrome (OSAHS) are regarded as consequences of its adverse effects on the cardiovascular system. Chronic intermittent hypoxia (CIH) induced by OSAHS can result in vascular endothelial injury, thus promoting development of atherosclerosis (AS). Studies have shown that CIH is an independent risk factor for the occurrence and development of AS, but the underlying mechanism remains unclear. Here, we review clinical and fundamental studies reported during the last 10 years on the occurrence and development of AS mediated by CIH, focusing on inflammation, oxidative stress, insulin resistance, cell apoptosis, vascular endothelial injury, platelet activation, and neuroendocrine disorders. This review will offer current evidence and perspective to researchers for the development of effective intervention strategies for OSAHS-related cardiocerebrovascular diseases.

  11. Roles and Mechanisms of Obstructive Sleep Apnea-Hypopnea Syndrome and Chronic Intermittent Hypoxia in Atherosclerosis: Evidence and Prospective

    Directory of Open Access Journals (Sweden)

    Linqin Ma

    2016-01-01

    Full Text Available The morbidity and mortality of obstructive sleep apnea-hypopnea syndrome (OSAHS are regarded as consequences of its adverse effects on the cardiovascular system. Chronic intermittent hypoxia (CIH induced by OSAHS can result in vascular endothelial injury, thus promoting development of atherosclerosis (AS. Studies have shown that CIH is an independent risk factor for the occurrence and development of AS, but the underlying mechanism remains unclear. Here, we review clinical and fundamental studies reported during the last 10 years on the occurrence and development of AS mediated by CIH, focusing on inflammation, oxidative stress, insulin resistance, cell apoptosis, vascular endothelial injury, platelet activation, and neuroendocrine disorders. This review will offer current evidence and perspective to researchers for the development of effective intervention strategies for OSAHS-related cardiocerebrovascular diseases.

  12. Understanding the Effect of Statins and Patient Adherence in Atherosclerosis via a Quantitative Systems Pharmacology Model Using a Novel, Hybrid, and Multi-Scale Approach

    Directory of Open Access Journals (Sweden)

    Cesar Pichardo-Almarza

    2017-09-01

    Full Text Available Background and Objective: Statins are one of the most prescribed drugs to treat atherosclerosis. They inhibit the hepatic HMG-CoA reductase, causing a reduction of circulating cholesterol and LDL levels. Statins have had undeniable success; however, the benefits of statin therapy crystallize only if patients adhere to the prescribed treatment, which is far away from reality since adherence decreases with time with around half of patients discontinue statin therapy within the first year. The objective of this work is to; firstly, demonstrate a formal in-silico methodology based on a hybrid, multiscale mathematical model used to study the effect of statin treatment on atherosclerosis under different patient scenarios, including cases where the influence of medication adherence is examined and secondly, to propose a flexible simulation framework that allows extensions or simplifications, allowing the possibility to design other complex simulation strategies, both interesting features for software development.Methods: Different mathematical modeling paradigms are used to present the relevant dynamic behavior observed in biological/physiological data and clinical trials. A combination of continuous and discrete event models are coupled to simulate the pharmacokinetics (PK of statins, their pharmacodynamic (PD effect on lipoproteins levels (e.g., LDL and relevant inflammatory pathways whilst simultaneously studying the dynamic effect of flow-related variables on atherosclerosis progression.Results: Different scenarios were tested showing the impact of: (1 patient variability: a virtual population shows differences in plaque growth for different individuals could be as high as 100%; (2 statin effect on atherosclerosis: it is shown how a patient with a 1-year statin treatment will reduce his plaque growth by 2–3% in a 2-year period; (3 medical adherence: we show that a patient missing 10% of the total number of doses could increase the plaque growth

  13. Creative Industries: Development Processes Under Contemporary Conditions of Globalization

    Directory of Open Access Journals (Sweden)

    Valerija Kontrimienė

    2017-06-01

    Full Text Available The article deals with the processes of developing creative industries under conditions of a growth in the worldwide economy and globalization, discloses the role of the sector of creative industries and shows its place in the system of the modern global economy. The paper presents a comparative analysis of theories and theoretical approaches intended for the sector of creative industries and its development as well as defines regularities and specificities characteristic of the development of creative industries. Particular attention is shifted on the growth and development of creative industries considering the current challenges of globalization and on the most important specificities of the developing sector in the context of the challenges of economic globalization. The paper examines the trends reflecting the place of the sector of creative industries in the economy of the modern world, including the tendencies indicating changes in the export of the products created in this sector. The article considers the issues of developing creative industries and reveals priorities of future research.

  14. Enabling optimal energy options under the Clean Development Mechanism

    International Nuclear Information System (INIS)

    Gilau, Asmerom M.; Van Buskirk, Robert; Small, Mitchell J.

    2007-01-01

    This paper addresses the cost effectiveness of renewable energy technologies in achieving low abatement costs and promoting sustainable developments under the Clean Development Mechanism (CDM). According to the results of our optimal energy option's analysis, at project scale, compared with a diesel-only energy option, photovoltaic (PV)-diesel (PVDB), wind-diesel (WDB) and PV-wind-diesel (PVWDB) hybrids are very cost-effective energy options. Moreover, energy options with high levels of renewable energy, including 100% renewables, have the lowest net present cost and they are already cost effective without CDM. On the other hand, while the removal of about 87% carbon dioxide emissions could be achieved at negative cost, initial investment could increase by a factor of 40, which is one of the primary barriers hindering wider renewable energy applications in developing countries, among others. Thus, in order to increase developing countries' participation in the carbon market, CDM policy should shift from a purely market-oriented approach to investigating how to facilitate renewable energy projects through barrier removal. Thus, we recommend that further research should focus on how to efficiently remove renewable energy implementation barriers as a means to improve developing countries' participation in meaningful emission reduction while at the same time meeting the needs of sustainable economic development

  15. Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study.

    Science.gov (United States)

    López-Cancio, Elena; Galán, Amparo; Dorado, Laura; Jiménez, Marta; Hernández, María; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Barallat, Jaume; Massuet, Anna; Alzamora, Maria Teresa; Dávalos, Antonio; Arenillas, Juan Francisco

    2012-10-01

    Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease. Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular

  16. Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Hajime Otani

    2013-01-01

    Full Text Available Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span.

  17. Development of experimental systems for material sciences under microgravity

    Science.gov (United States)

    Tanii, Jun; Obi, Shinzo; Kamimiyata, Yotsuo; Ajimine, Akio

    1988-01-01

    As part of the Space Experiment Program of the Society of Japanese Aerospace Companies, three experimental systems (G452, G453, G454) have been developed for materials science studies under microgravity by the NEC Corporation. These systems are to be flown as Get Away Special payloads for studying the feasibility of producing new materials. Together with the experimental modules carrying the hardware specific to the experiment, the three systems all comprise standard subsystems consisting of a power supply, sequence controller, temperature controller, data recorder, and video recorder.

  18. A CD1d-dependent lipid antagonist to NKT cells ameliorates atherosclerosis in ApoE-/- mice by reducing lesion necrosis and inflammation.

    Science.gov (United States)

    Li, Yi; Kanellakis, Peter; Hosseini, Hamid; Cao, Anh; Deswaerte, Virginie; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

    2016-02-01

    Atherosclerosis-related deaths from heart attacks and strokes remain leading causes of global mortality, despite the use of lipid-lowering statins. Thus, there is an urgent need to develop additional therapies. Reports that NKT cells promote atherosclerosis and an NKT cell CD1d-dependent lipid antagonist (DPPE-PEG350, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-350]) reduces allergen-induced inflammation led us to investigate its therapeutic potential in preventing the development and progression of experimental atherosclerosis. DPPE-PEG350 was administered to hyperlipidaemic ApoE(-/-) mice with/without established atherosclerosis. Atherosclerosis and immune cells were assessed in the aortic sinus lesions. Lesion expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) responsible for inflammatory immune cell recruitment as well as mRNA expression of IFNγ and its plasma levels were investigated. Necrotic cores and lesion smooth muscle and collagen contents important in plaque stability were determined as were plasma lipid levels. DPPE-PEG350 reduced atherosclerosis development and delayed progression of established atherosclerosis without affecting plasma lipids. CD4 and CD8 T cells and B cells in atherosclerotic lesions were decreased in DPPE-PEG350-treated mice. Lesion MCP-1 and VCAM-1 protein expression and necrotic core size were reduced without affecting lesion smooth muscle and collagen content. IFNγ and lymphocytes were unaffected by the treatment. The attenuation of progression of established atherosclerosis together with reduced development of atherosclerosis in hyperlipidaemic mice by the NKT antagonist, without affecting NKT cell or other lymphocyte numbers, suggests that targeting lesion inflammation via CD1d-dependent activation of NKT cells using DPPE-PEG350 has a therapeutic potential in treating atherosclerosis. Published on behalf of the European Society of

  19. Mixed Transportation Network Design under a Sustainable Development Perspective

    Directory of Open Access Journals (Sweden)

    Jin Qin

    2013-01-01

    Full Text Available A mixed transportation network design problem considering sustainable development was studied in this paper. Based on the discretization of continuous link-grade decision variables, a bilevel programming model was proposed to describe the problem, in which sustainability factors, including vehicle exhaust emissions, land-use scale, link load, and financial budget, are considered. The objective of the model is to minimize the total amount of resources exploited under the premise of meeting all the construction goals. A heuristic algorithm, which combined the simulated annealing and path-based gradient projection algorithm, was developed to solve the model. The numerical example shows that the transportation network optimized with the method above not only significantly alleviates the congestion on the link, but also reduces vehicle exhaust emissions within the network by up to 41.56%.

  20. Mixed Transportation Network Design under a Sustainable Development Perspective

    Science.gov (United States)

    Qin, Jin; Ni, Ling-lin; Shi, Feng

    2013-01-01

    A mixed transportation network design problem considering sustainable development was studied in this paper. Based on the discretization of continuous link-grade decision variables, a bilevel programming model was proposed to describe the problem, in which sustainability factors, including vehicle exhaust emissions, land-use scale, link load, and financial budget, are considered. The objective of the model is to minimize the total amount of resources exploited under the premise of meeting all the construction goals. A heuristic algorithm, which combined the simulated annealing and path-based gradient projection algorithm, was developed to solve the model. The numerical example shows that the transportation network optimized with the method above not only significantly alleviates the congestion on the link, but also reduces vehicle exhaust emissions within the network by up to 41.56%. PMID:23476142

  1. Subclinical thyroid dysfunction and risk of carotid atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Hosu Kim

    Full Text Available The effect of subclinical thyroid dysfunction on vascular atherosclerosis remains uncertain. The objective of this study was to elucidate the association between sustained subclinical thyroid dysfunction and carotid plaques, which are an early surrogate marker of systemic atherosclerosis.The study included 21,342 adults with consistent thyroid hormonal status on serial thyroid function tests (TFTs and carotid artery duplex ultrasonography at a health screening center between 2007 and 2014. The effect of subclinical thyroid dysfunction on baseline carotid plaques and newly developed carotid plaques during 5-year follow-up was determined by logistic regression analyses and GEE (Generalized Estimating Equations, respectively.Carotid plaques were more common in the subclinical hypothyroidism (55.6% than the euthyroidism (47.8% at baseline. However, in multivariable analysis, thyroid status was not a significant risk for the carotid plaques at baseline. Instead, traditional cardiovascular risk factors, such as age (P <0.001, systolic blood pressure (P = 0.023, fasting blood glucose (P = 0.030, and creatinine (P = 0.012 were associated with baseline carotid plaques in subclinical hypothyroidism. In longitudinal analyses of subjects who were followed up for more than 5 years, there was no significant difference in the cumulative incidence of new carotid plaques according to time between subjects with subclinical hypothyroidism and those with euthyroidism (P = 0.392.Sustained subclinical thyroid dysfunction did not affect the baseline or development of carotid plaques in healthy individuals.

  2. Coronary atherosclerosis: Significance of autophagic armour.

    Science.gov (United States)

    Arora, Mansi; Kaul, Deepak

    2012-09-26

    Autophagy is a lysosomal degradation pathway of cellular components such as organelles and long-lived proteins. Though a protective role for autophagy has been established in various patho-physiologic conditions such as cancer, neurodegeneration, aging and heart failure, a growing body of evidence now reveals a protective role for autophagy in atherosclerosis, mainly by removing oxidatively damaged organelles and proteins and also by promoting cholesterol egress from the lipid-laden cells. Recent studies by Razani et al and Liao et al unravel novel pathways that might be involved in autophagic protection and in this commentary we highlight the importance of autophagy in atherosclerosis in the light of these two recent papers.

  3. Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

    Science.gov (United States)

    Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

    2016-02-01

    Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

  4. Atherosclerosis and atherosensitivity in two southwest Algerian desert rodents, Psammomys obesus and Gerbillus gerbillus, and in Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    El-Aoufi S

    2012-09-01

    Full Text Available Salima El-Aoufi,1 Mohamed-Amine Lazourgui,1 Lakhdar Griene,2 Boubekeur Maouche31Laboratoire de Biologie et de Physiologie des Organismes/MMDED, Faculté des Sciences Biologiques, USTHB, El-Alia, Dar El Beida, Algeria; 2Laboratoire d'Hormonologie, Centre Pierre et Marie Curie, C.H.U Mustapha, Algeria; 3Laboratoire de Physicochimie Théorique et Chimie Informatique, Faculté de Chimie, USTHB, El-Alia, Dar El Beida, AlgeriaAbstract: Cardiovascular disease, including atherosclerosis, is the leading cause of death in patients with diabetes worldwide; thus, it is a major medical concern. The endothelium contributes to the control of many vascular functions, and clinical observations show that it is a primary target for diabetic syndrome. To get better insight into the mechanisms underlying atherosclerosis, we studied the interspecific differences in the arterial metabolisms of two, Psammomys obesus and Gerbillus gerbillus, as well as Rattus norvegicus (Wistar rat, well known for its atheroresistance. Twenty-two enzymatic activities and six macromolecular substances were histochemically compared in the two desert species and in Wistar aortas (abdominal and thoracic and arteries (femoral and caudal embedded in a common block. In the healthy adult rodents, enzyme activities were very intense. They demonstrated that aortic myocytes are capable of various synthesis and catabolism processes. However, considering the frequency of atherosclerosis and its phenotypes, significant differences appeared between the species studied. Our comparative study shows that aortic atherosensitive animals have several common metabolic characteristics, which are found in Psammomys rich in metachromatic glycosaminoglycans (involved in the inhibition of lipolysis and in calcification of the organic matrix, reduced activity in enzymes related to the Krebs cycle (weakening energetic power, and low lipolytic enzyme, adenosine triphosphatase, and adenosine diphosphatase activities

  5. RENAL INVOLVEMENT IN SUBJECTS WITH PERIPHERAL ATHEROSCLEROSIS

    International Nuclear Information System (INIS)

    FAWZY, A.; IBRAHIM, S.

    2008-01-01

    Ischemic nephropathy is an important cause of renal failure.Sub-clinical renal function abnormalities may exist in patients with extra renal atherosclerosis and may precede the onset of overt ischemic nephropathy. To assess the impact of extrarenal atherosclerosis on the kidney, the study evaluated renal function in 50 subjects with differing degrees of peripheral atherosclerosis without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension.All laboratory testing including total LDL and HDL-cholesterol, triglycerides, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance) were determined as well as smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). The results showed no change in plasma creatinine while DTPA clearance was increased from 91.58±26.53 to 93.47±24.82 ml/min/1.73 m. MAG3 clearance was progressively declined with the severity of vascular damage from 244.86 ± 60.60 to 173.59±58.74 ml/min/1.73 m.Stepwise, multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized B coefficient -0.40; P< 0.001), smoking habit (-0.34;P=0.004) and serum LDL-cholesterol (-0.24; P<0.035).It could be concluded that the renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors

  6. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming

    DEFF Research Database (Denmark)

    Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S

    2016-01-01

    -containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound...... of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis....

  7. An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA).

    Science.gov (United States)

    Liang, C Jason; Budoff, Matthew J; Kaufman, Joel D; Kronmal, Richard A; Brown, Elizabeth R

    2012-07-02

    Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA). Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

  8. An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA

    Directory of Open Access Journals (Sweden)

    Liang C

    2012-07-01

    Full Text Available Abstract Background Extent of atherosclerosis measured by amount of coronary artery calcium (CAC in computed tomography (CT has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS. These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA. Methods Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA. The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Results Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26 and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179. Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224. The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. Conclusions The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

  9. Incretin hormones as immunomodulators of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Nuria eAlonso

    2012-09-01

    Full Text Available Atherosclerosis results from endothelial cell dysfunction and inflammatory processes affecting both macro-and microvasculature which are involved in vascular diabetic complications. Glucagon-like peptide 1 (GLP-1 is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally as opposed to intravenously and it retains its insulinotropic activity in patients with type 2 diabetes mellitus (T2D. GLP-1 based therapies, such as GLP-1 receptor (R agonists and inhibitors of dipeptidyl peptidase 4 (DPP-4, an enzyme that degrades endogenous GLP-1 are routinely used to treat patients with T2D. Recent experimental model studies have established that GLP-1R mRNA is widely expressed in several immune cells. Moreover, its activation contributes to the regulation of both thymocyte and peripheral T cells proliferation and is involved in the maintenance of peripheral regulatory T cells. GLP-1 R is also expressed in endothelial and smooth muscle cells. The effect of incretin hormones on atherosclerogenesis have recently been studied in animal models of apolipoprotein E-deficient mice (apo E-/-. These studies have demonstrated that treatment with incretin hormones or related compounds suppresses the progression of atherosclerosis and macrophage infiltration in the arterial wall as well as a marked anti-oxidative and anti-inflammatory effect on endothelial cells. This effect may have a major impact on the attenuation of atherosclerosis and may help in the design of new therapies for cardiovascular disease in patients with type 2 diabetes.

  10. Atherosclerosis in epilepsy: its causes and implications.

    Science.gov (United States)

    Hamed, Sherifa A

    2014-12-01

    Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

    International Nuclear Information System (INIS)

    Wu, M.-M.; Chiou, H.-Y.; Hsueh, Y.-M.; Hong, C.-T.; Su, C.-L.; Chang, S.-F.; Huang, W.-L.; Wang, H.-T.; Wang, Y.-H.; Hsieh, Y.-C.; Chen, C.-J.

    2006-01-01

    Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA V ) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA V (MMA%) was calculated by dividing with total arsenic species in urine, including arsenite, arsenate, MMA V , and dimethylarsinic acid (DMA V ). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% (≥16.5%) and high homocysteine levels (≥12.7 μmol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 μmol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine

  12. Abnormalities of blood platelets in rabbits with dietary hypercholesterolemia and atherosclerosis

    International Nuclear Information System (INIS)

    Mazoyer, E.; Dalal, K.; Carpenter, D.; Brennan, K.; Yee, T.; Mazoyer, B.; Leven, R.; Ebbe, S.

    1986-01-01

    Preliminary results are reported from observations of rabbits that were fed a high cholesterol diet to induce atherosclerosis. The purpose of the project was to develop an animal model that would be appropriate to use in the imaging of vascular lesions by positron emission tomography or other techniques

  13. Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults

    NARCIS (Netherlands)

    Keustermans, G C; Kofink, Daniel; Eikendal, A.L.; de Jager, W.; Meerding, J.; Nuboer, R.; Waltenberger, J.; Kraaijeveld, A.O.; Jukema, J Wouter; Sels, J.W.; Garssen, J; Prakken, Berent J.; Asselbergs, Folkert W; Kalkhoven, E.; Hoefer, Imo E.; Pasterkamp, G.; Schipper, Henk S

    2017-01-01

    Childhood obesity coincides with increased numbers of circulating classical CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes

  14. A case of primary hypothyroidism causing central nervous system atherosclerosis in a dog.

    Science.gov (United States)

    Blois, Shauna L; Poma, Roberto; Stalker, Margaret J; Allen, Dana G

    2008-08-01

    A 2-year-old, castrated male, Australian shepherd was presented with a history of chronic mild ataxia, obesity, and lethargy. The dog was treated with levothyroxine, but the ataxia worsened. Cranial nerve abnormalities developed and the dog was euthanized. Postmortem examination revealed marked thyroid gland atrophy and widespread, severe central nervous system atherosclerosis.

  15. Hemoglobin and atherosclerosis in patients with manifest arterial disease. The SMART-study

    NARCIS (Netherlands)

    Dijk, J. M.; Wangge, G.; Graaf, Y. van der; Bots, M. L.; Grobbee, D. E.; Algra, A.

    2006-01-01

    Decreased hemoglobin levels are known to be associated with an increased risk of coronary mortality and morbidity. This is largely thought to result from the development of left ventricular hypertrophy. Similar remodeling mechanisms of the vessel wall that may result in atherosclerosis are likely to

  16. Peculiarities of Corporate Culture Development under Conditions of Remote Working

    Directory of Open Access Journals (Sweden)

    Shchetinina Ludmila V

    2015-03-01

    Full Text Available The paper analyzes the significance and peculiarities of corporate culture formation for remote employees. Particular attention is paid to instruments that allow creating a team in the absence of the usual office environment. There have been defined the signs of trust manifestation that distinguish the corporate culture in a team with experience of teamwork and without such experience — a level of weakness manifestation and recognition of mistakes, presence of critics from colleagues, asking for recourse, interest in colleagues’ experience and skills. According to the signs the necessary management practices for the development and creation of the corporate culture has been offered. It is noted that the team with the experience of teamwork at the early stages acts quite consistently adhering to the declared standards, rules and basic values. However, even under these conditions, the corporate culture is growing weaker in time. And here it would be helpful to use the management practices that do not replace personal contact but are maximally close to it. All management practices are classified in accordance with the directions of the corporate culture development, namely, creation of effective social intranet, establishment of quality communication, transparent motivation and clear description of the control sequences, description and establishment of clear guidelines, development of personal effectiveness of employees, simplification of the project communication process, creation of “virtual coolers”, the philosophy of “getting into the body” of a remote employee, monitoring professional burnout, etc.

  17. Integrated Bali Cattle Development Model Under Oil Palm Plantation

    Directory of Open Access Journals (Sweden)

    Rasali Hakim Matondang

    2015-09-01

    Full Text Available Bali cattle have several advantages such as high fertility and carcass percentage, easy adaptation to the new environment as well. Bali cattle productivity has not been optimal yet. This is due to one of the limitation of feed resources, decreasing of grazing and agricultural land. The aim of this paper is to describe Bali cattle development integrated with oil palm plantations, which is expected to improve productivity and increase Bali cattle population. This integration model is carried out by raising Bali cattle under oil palm plantation through nucleus estate scheme model or individual farmers estates business. Some of Bali cattle raising systems have been applied in the integration of palm plantation-Bali cattle. One of the intensive systems can increase daily weight gain of 0.8 kg/head, calfcrop of 35% per year and has the potency for industrial development of feed and organic fertilizer. In the semi-intensive system, it can improve the production of oil palm fruit bunches (PFB more than 10%, increase harvested-crop area to 15 ha/farmer and reduce the amount of inorganic fertilizer. The extensive system can produce calfcrop ³70%, improve ³30% of PFB, increase business scale ³13 cows/farmer and reduce weeding costs ³16%. Integrated Bali cattle development may provide positive added value for both, palm oil business and cattle business.

  18. Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.

    Science.gov (United States)

    Wang, Chuan; Nishijima, Kazutoshi; Kitajima, Shuji; Niimi, Manabu; Yan, Haizhao; Chen, Yajie; Ning, Bo; Matsuhisa, Fumikazu; Liu, Enqi; Zhang, Jifeng; Chen, Y Eugene; Fan, Jianglin

    2017-07-01

    Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates. On a chow diet, hepatic expression of human EL in Tg rabbits led to remarkable reductions in plasma levels of total cholesterol, phospholipids, and high-density lipoprotein-cholesterol compared with non-Tg controls. On a cholesterol-rich diet for 16 weeks, Tg rabbits exhibited significantly lower hypercholesterolemia and less atherosclerosis than non-Tg littermates. In Tg rabbits, gross lesion area of aortic atherosclerosis was reduced by 52%, and the lesions were characterized by fewer macrophages and smooth muscle cells compared with non-Tg littermates. Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis. © 2017 American Heart Association, Inc.

  19. PPARα activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH.

    Science.gov (United States)

    Baron, Morgane; Leroyer, Aurélie S; Majd, Zouher; Lalloyer, Fanny; Vallez, Emmanuelle; Bantubungi, Kadiombo; Chinetti-Gbaguidi, Giulia; Delerive, Philippe; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne

    2011-09-01

    Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are complex pathologies characterized by lipid accumulation, chronic inflammation and extensive tissue remodelling. Microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, might not only be biomarkers, but also functional actors in these pathologies. The apoE2-KI mouse is a model of atherosclerosis and NAFLD. Activation of the nuclear receptor PPARα decreases atherosclerosis and components of non-alcoholic steatohepatitis (NASH) in the apoE2-KI mouse. (1) To determine whether MPs are present in atherosclerotic lesions, liver and plasma during atherosclerosis and NASH progression in apoE2-KI mice, and (2) to study whether PPARα activation modulates MP concentrations. ApoE2-KI mice were fed a Western diet to induce atherosclerosis and NASH. MPs were isolated from atherosclerotic lesions, liver and blood and quantified by flow cytometry. An increase of MPs was observed in the atherosclerotic lesions and in the liver of apoE2-KI mice upon Western diet feeding. PPARα activation with fenofibrate decreased MP levels in the atherosclerotic lesions in a PPARα-dependent manner, but did not influence MP concentrations in the liver. Here we report that MPs are present in atherosclerotic lesions and in the liver of apoE2-KI mice. Their concentration increased during atherosclerosis and NASH development. PPARα activation differentially modulates MP levels in a tissue-specific manner. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Development of Shale Gas Supply Chain Network under Market Uncertainties

    Directory of Open Access Journals (Sweden)

    Jorge Chebeir

    2017-02-01

    Full Text Available The increasing demand of energy has turned the shale gas and shale oil into one of the most promising sources of energy in the United States. In this article, a model is proposed to address the long-term planning problem of the shale gas supply chain under uncertain conditions. A two-stage stochastic programming model is proposed to describe and optimize the shale gas supply chain network. Inherent uncertainty in final products’ prices, such as natural gas and natural gas liquids (NGL, is treated through the utilization of a scenario-based method. A binomial option pricing model is utilized to approximate the stochastic process through the generation of scenario trees. The aim of the proposed model is to generate an appropriate and realistic supply chain network configuration as well as scheduling of different operations throughout the planning horizon of a shale gas development project.

  1. A clinically applicable adjuvant for an atherosclerosis vaccine in mice.

    Science.gov (United States)

    Kobiyama, Kouji; Vassallo, Melanie; Mitzi, Jessica; Winkels, Holger; Pei, Hong; Kimura, Takayuki; Miller, Jacqueline; Wolf, Dennis; Ley, Klaus

    2018-06-22

    Vaccination with MHC-II-restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen-specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe-deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene oil similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL-10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene-based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

    Science.gov (United States)

    Siasos, Gerasimos; Tsigkou, Vasiliki; Kokkou, Eleni; Oikonomou, Evangelos; Vavuranakis, Manolis; Vlachopoulos, Charalambos; Verveniotis, Alexis; Limperi, Maria; Genimata, Vasiliki; Papavassiliou, Athanasios G; Stefanadis, Christodoulos; Tousoulis, Dimitris

    2014-01-01

    It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health.

  3. Wine, alcohol and atherosclerosis: clinical evidences and mechanisms

    Directory of Open Access Journals (Sweden)

    P.L. da Luz

    2004-09-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease which may cause obstructions of the coronary, cerebral and peripheral arteries. It is typically multifactorial, most often dependent on risk factors such as hypercholesterolemia, diabetes, smoking, hypertension, sedentarism, and obesity. It is the single main cause of death in most developed countries due to myocardial infarction, angina, sudden death, and heart failure. Several epidemiological studies suggest that moderate alcohol intake, especially red wine, decrease cardiac mortality due to atherosclerosis. The alcohol effect is described by a J curve, suggesting that moderate drinkers may benefit while abstainers and heavy drinkers are at higher risk. Experimental studies indicate that most beneficial effects of drinking are attributable to flavonoids that are present in red wine, purple grape juice and several fruits and vegetables. The mechanisms include antiplatelet actions, increases in high-density lipoprotein, antioxidation, reduced endothelin-1 production, and increased endothelial nitric oxide synthase expression which causes augmented nitric oxide production by endothelial cells. These findings lead to the concept that moderate red wine drinking, in the absence of contraindications, may be beneficial to patients who are at risk of atherosclerotic cardiovascular events. Moreover, a diet based on fruits and vegetables containing flavonoids may be even more beneficial.

  4. Power generation capacity planning under budget constraint in developing countries

    International Nuclear Information System (INIS)

    Afful-Dadzie, Anthony; Afful-Dadzie, Eric; Awudu, Iddrisu; Banuro, Joseph Kwaku

    2017-01-01

    Highlights: • A long term stochastic GEP model with budget constraint is developed. • Model suitable for analyzing GEP problems in developing countries. • Model determines optimal mix, size and timing of future generation capacity needs. • A real case study of the Ghana GEP problem was employed. • Insufficient budget leads to costly generation capacity expansion plans. - Abstract: This paper presents a novel multi-period stochastic optimization model for studying long-term power generation capacity planning in developing countries. A stylized model is developed to achieve three objectives: (1) to serve as a tool for determining optimal mix, size and timing of power generation types in the face of budget constraint, (2) to help decision makers appreciate the consequences of capacity expansion decisions on level of unserved electricity demand and its attendant impact on the national economy, and (3) to encourage the habit of periodic savings towards new generation capacity financing. The problem is modeled using a stochastic mixed-integer linear programming (MILP) technique under demand uncertainty. The effectiveness of the model, together with valuable insights derived from considering different levels of budget constraints are demonstrated using Ghana as a case study. The results indicate that at an annual savings equivalent to 0.75% of GDP, Ghana could finance the needed generation capacity to meet approximately 95% of its annual electricity demand between 2016 and 2035. Additionally, it is observed that as financial constraint becomes tighter, decisions on the mix of new generation capacities tend to be more costly compared to when sufficient funds are available.

  5. Function of CD147 in atherosclerosis and atherothrombosis

    Science.gov (United States)

    Wang, Cuiping; Jin, Rong; Zhu, Xiaolei; Yan, Jinchuan; Guohong, Li

    2015-01-01

    CD147, a member of the immunoglobulin super family, is a well-known potent inducer of extracellular matrix metalloproteinases. Studies show that CD147 is upregulated in inflammatory diseases. Atherosclerosis is a chronic inflammatory disease of the artery wall. Further understanding of the functions of CD147 in atherosclerosis and atherothrombosis may provide a new strategy for preventing and treating cardiovascular disease. In this review, we discuss how CD147 contributes to atherosclerosis and atherothrombosis. PMID:25604960

  6. Development switch in neural circuitry underlying odor-malaise learning.

    Science.gov (United States)

    Shionoya, Kiseko; Moriceau, Stephanie; Lunday, Lauren; Miner, Cathrine; Roth, Tania L; Sullivan, Regina M

    2006-01-01

    Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.

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

    Directory of Open Access Journals (Sweden)

    D. Thompson

    2017-08-01

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

  8. New product development projects evaluation under time uncertainty

    Directory of Open Access Journals (Sweden)

    Thiago Augusto de Oliveira Silva

    2009-12-01

    Full Text Available The development time is one of the key factors that contribute to the new product development success. In spite of that, the impact of the time uncertainty on the development has been not fully exploited, as far as decision supporting models to evaluate this kind of projects is concerned. In this context, the objective of the present paper is to evaluate the development process of new technologies under time uncertainty. We introduce a model which captures this source of uncertainty and develop an algorithm to evaluate projects that incorporates Monte Carlo Simulation and Dynamic Programming. The novelty in our approach is to thoroughly blend the stochastic time with a formal approach to the problem, which preserves the Markov property. We base our model on the distinction between the decision epoch and the stochastic time. We discuss and illustrate the applicability of our model through an empirical example.O tempo de desenvolvimento é um dos fatores-chave que contribuem para o sucesso do desenvolvimento de novos produtos. Apesar disso, o impacto da incerteza de tempo no desenvolvimento tem sido pouco considerado em modelos de avaliação e valoração deste tipo de projetos. Neste contexto, este trabalho tem como objetivo avaliar projetos de desenvolvimento de novas tecnologias mediante o tempo incerto. Introduzimos um modelo capaz de captar esta fonte de incerteza e desenvolvemos um algoritmo para a valoração do projeto que integra Simulação de Monte Carlo e Programação Dinâmica. A novidade neste trabalho é conseguir integrar meticulosamente o tempo estocástico a uma estrutura formal para tomada de decisão que preserva a propriedade de Markov. O principal ponto para viabilizar este fato é distinção entre o momento de revisão e o tempo estocástico. Ilustramos e discutimos a aplicabilidade deste modelo por meio de um exemplo empírico.

  9. Nanoparticles containing a liver X receptor agonist inhibit inflammation and atherosclerosis.

    Science.gov (United States)

    Zhang, Xue-Qing; Even-Or, Orli; Xu, Xiaoyang; van Rosmalen, Mariska; Lim, Lucas; Gadde, Suresh; Farokhzad, Omid C; Fisher, Edward A

    2015-01-28

    Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR is significantly more effective than free GW3965 at inducing LXR-target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr (-/-) mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP-LXR over 2 weeks markedly reduce the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine.

    Science.gov (United States)

    Fan, Jianglin; Kitajima, Shuji; Watanabe, Teruo; Xu, Jie; Zhang, Jifeng; Liu, Enqi; Chen, Y Eugene

    2015-02-01

    Laboratory animal models play an important role in the study of human diseases. Using appropriate animals is critical not only for basic research but also for the development of therapeutics and diagnostic tools. Rabbits are widely used for the study of human atherosclerosis. Because rabbits have a unique feature of lipoprotein metabolism (like humans but unlike rodents) and are sensitive to a cholesterol diet, rabbit models have not only provided many insights into the pathogenesis and development of human atherosclerosis but also made a great contribution to translational research. In fact, rabbit was the first animal model used for studying human atherosclerosis, more than a century ago. Currently, three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (1) cholesterol-fed rabbits, (2) Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, and (3) genetically modified (transgenic and knock-out) rabbits. Despite their importance, compared with the mouse, the most widely used laboratory animal model nowadays, the use of rabbit models is still limited. In this review, we focus on the features of rabbit lipoprotein metabolism and pathology of atherosclerotic lesions that make it the optimal model for human atherosclerotic disease, especially for the translational medicine. For the sake of clarity, the review is not an attempt to be completely inclusive, but instead attempts to summarize substantial information concisely and provide a guideline for experiments using rabbits. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Developing State Level Approaches under the State Level Concept

    International Nuclear Information System (INIS)

    Budlong Sylvester, K.; Murphy, C.L.; Boyer, B.; Pilat, J.F.

    2015-01-01

    With the pursuit of the State-Level Concept (SLC), the IAEA has sought to further evolve the international safeguards system in a manner which maintains (or improves) the effectiveness of the system in an environment of expanding demands and limited resources. The IAEA must not remain static and should continuously examine its practices to ensure it can capture opportunities for cost reductions while adapting to, and staying ahead of, emerging proliferation challenges. Contemporary safeguards have been focused on assessing the nuclear programme of the State as a whole, rather than on the basis of individual facilities. Since the IAEA's integrated safeguards program, State-level Approaches (SLAs) have been developed that seek to optimally combine the measures provided for by the Additional Protocol with those of traditional safeguards. This process resulted in facility specific approaches that, while making use of a State's broader conclusion, were nonetheless prescriptive. Designing SLAs on a State-by-State basis would avoid the shortcomings of a one-size-fits-all system. It would also enable the effective use of the Agency's information analysis and State evaluation efforts by linking this analysis to safeguards planning efforts. Acquisition Path Analysis (APA), along with the State Evaluation process, can be used to prioritize paths in a State in terms of their attractiveness for proliferation. While taking advantage of all safeguards relevant information, and tailoring safeguards to individual characteristics of the State, paths of the highest priority in all States will necessarily meet the same standard of coverage. Similarly, lower priority paths will have lower performance targets, thereby promoting nondiscrimination. Such an approach would improve understanding of safeguards implementation under the SLC and the rational for safeguards resource allocation. The potential roles for APA and performance targets in SLA development will be reviewed

  12. Is zinc deficiency a risk factor for atherosclerosis?

    Science.gov (United States)

    Beattie, John H; Kwun, In-Sook

    2004-02-01

    The development of atherosclerosis is influenced by genetic, lifestyle and nutritional risk factors. Zn and metallothionein deficiency can enhance oxidative-stress-related signalling processes in endothelial cells, and since changes in available plasma Zn may affect the Zn status of the endothelium, Zn deficiency could be a risk factor for IHD. Although the association of Zn with many proteins is essential for their function, three key signalling processes are highlighted as being principal targets for the effect of Zn deficiency: the activation of NF-kappaB, the activation of caspase enzymes and the signalling of NO. The need to develop a reliable indicator of Zn status is critical to any epidemiological approach for studying the relationship between Zn status and disease incidence. Studies using appropriate animal models and investigating how the plasma Zn pool influences endothelial intracellular labile Zn would be helpful in appreciating the importance of Zn deficiency in atherogenesis.

  13. Current and Under Development Treatment Modalities of Psoriasis: A Review.

    Science.gov (United States)

    Albaghdadi, Abdullah

    2017-01-01

    Psoriasis is a chronic and complex autoimmune inflammatory skin disease that affects over 125 million people worldwide. It can exhibit at any age, in spite of the fact that children are less normally influenced than adults. It is characterized by distinct erythematous plaques shielded with conspicuous silvery scales that shows up in different areas of the skin. Knowledge of pathophysiology, especially the pathogenesis of psoriasis, has significantly progressed in the recent decade. Advancement in molecular knowledge leads to better understanding of the disease, thus influencing the development of efficient treatment modalities. However, even with the availability of various options of treatment most of the efficient treatment modalities are costly. Expenses of health care bring about major financial weight to the patients as well as to health care systems. Thus, it was important to review the available current treatment options and those which are under development, in terms of efficacy, safety and cost to assist in selecting the most appropriate treatment for psoriasis patients. Literatures were searched by using key words psoriasis, topical treatment, systemic treatment, biologics and phototherapies, on Embase, Medline, Jstor, Cochrane and Merck Index databases. Life-style choices such as smoking, alcohol consumption, obesity and stress are recognised as risk factors and triggers associated with psoriasis. Psoriasis poses psycho-social and economic burden on affected patients that sometimes leads to depression, reduced social interaction and suicidal tendencies in patients. Depending on the type, severity and extent of the disease, comorbidities, patient preference, efficacy and safety profile, numerous treatment modalities and therapeutic agents are available such as topical, systemic, biologic and phototherapeutic treatments. However, it was found that among all the current available treatments for psoriasis, biologic agents and phototherapeutic modalities are

  14. Impact of Prediabetic Status on Coronary Atherosclerosis

    Science.gov (United States)

    Kurihara, Osamu; Takano, Masamichi; Yamamoto, Masanori; Shirakabe, Akihiro; Kimata, Nakahisa; Inami, Toru; Kobayashi, Nobuaki; Munakata, Ryo; Murakami, Daisuke; Inami, Shigenobu; Okamatsu, Kentaro; Ohba, Takayoshi; Ibuki, Chikao; Hata, Noritake; Seino, Yoshihiko; Mizuno, Kyoichi

    2013-01-01

    OBJECTIVE To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09–55.6], P = 0.005; and OR 4.13 [95% CI 1.01–17.0], P = 0.049, respectively). CONCLUSIONS Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself. PMID:23223344

  15. Nutrigenetics and nutrigenomics of atherosclerosis.

    Science.gov (United States)

    Merched, Aksam J; Chan, Lawrence

    2013-06-01

    The latest genome-wide association studies (GWAS) have re-energized our effort to understand the genetic basis of atherosclerotic cardiovascular disease. Although the knowledge generated by GWAS has confirmed that mediators of inflammation and perturbed lipid metabolism are major players in cardiovascular disease (CVD) development, much of individual disease heritability remains unexplained by the variants identified through GWAS. Moreover, results from interventions that aim at the pharmaceutical modification of lipid parameters fall short of expectation. These elusive treatment goals based on heritability studies highlight a key supportive, and perhaps even primary, role of nutritional therapy to achieve better health outcomes. Nonetheless, effective and specific interventions for CVD prevention using principles of "personalized" nutrition require a better knowledge of gene-diet interactions, an area that remains poorly explored. Dietary fatty acids such as omega-3 polyunsaturated fatty acids (PUFAs) are an excellent example of a widely studied "environment" that interacts with the genetic makeup in relation to CVD. A thorough exploration of the nutrigenomics and nutrigenetics of omega-3 PUFAs is key to understanding the etiology, and developing effective preventive measures. In this review, we will summarize the current state of knowledge of genetic interactions with omega-3 PUFAs in modulating lipid metabolism and inflammation, and defining health outcomes. Nutrigenetics and nutrigenomics are still in their infancy with respect to CVD prediction and therapy. Integration of the progress in the omics, including metabolomics, lipidomics, transcriptomics, and proteomics, coupled with advances in nutrigenomic and nutrigenetic research will move us towards personalized medicine as the ultimate paradigm of responsible clinical practice.

  16. Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings.

    Science.gov (United States)

    Madan, Monika; Amar, Salomon

    2008-09-12

    Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/-) mice. To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/-)-TLR2(+/+), ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 microl live Porphyromonas gingivalis (P.g) (10(7) CFU) or vehicle (normal saline). Animals were euthanized 24 weeks after the first inoculation. ApoE(+/-)-TLR2(+/+) mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE(+/-)-TLR2(+/+) mice were significantly higher than from ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE(+/-)-TLR2(+/+) mice compared to ApoE(+/-)-TLR2(+/-) and TLR2(-/-) mice, irrespective of diet or bacterial challenge. ApoE(+/-)-TLR2(+/+) mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist) also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE(+/-)-TLR2(-/-) mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS) of aortic samples analyzed by 2-dimensional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE(+/-)-TLR2(+/+) mice

  17. Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings.

    Directory of Open Access Journals (Sweden)

    Monika Madan

    2008-09-01

    Full Text Available Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/- mice.To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/--TLR2(+/+, ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 microl live Porphyromonas gingivalis (P.g (10(7 CFU or vehicle (normal saline. Animals were euthanized 24 weeks after the first inoculation. ApoE(+/--TLR2(+/+ mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE(+/--TLR2(+/+ mice were significantly higher than from ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE(+/--TLR2(+/+ mice compared to ApoE(+/--TLR2(+/- and TLR2(-/- mice, irrespective of diet or bacterial challenge. ApoE(+/--TLR2(+/+ mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE(+/--TLR2(-/- mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS of aortic samples analyzed by 2-dimensional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE(+/--TLR2(+/+ mice fed the high fat

  18. [Psychosocial factors as predictors of atherosclerosis and cardiovascular events: contribution from animal models].

    Science.gov (United States)

    Alboni, Paolo; Alboni, Marco

    2006-11-01

    investigated. As regards the biological mechanisms of chronic stress, the hypothalamic-pituitary-adrenal axis and the sympathetic system have been investigated. The studies have mainly been carried out on primates, and, to a less extent, on other mammals such as rabbit and wolf and on some species of birds. In the animals under social isolation, subordination or hostility/anger, a significantly more severe atherosclerosis was present, besides an increased activity of the hypothalamic-pituitary-adrenal axis and sympathetic system. In conclusion, the results offered by animal models seem to satisfy the first of Kuller's criteria, as for the three above-mentioned psychosocial factors.

  19. Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9.

    Science.gov (United States)

    Lupia, Enrico; Zheng, Feng; Grosjean, Fabrizio; Tack, Ivan; Doublier, Sophie; Elliot, Sharon J; Vlassara, Helen; Striker, Gary E

    2012-02-01

    Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis.

  20. Agent Based Modeling of Atherosclerosis: A Concrete Help in Personalized Treatments

    Science.gov (United States)

    Pappalardo, Francesco; Cincotti, Alessandro; Motta, Alfredo; Pennisi, Marzio

    Atherosclerosis, a pathology affecting arterial blood vessels, is one of most common diseases of the developed countries. We present studies on the increased atherosclerosis risk using an agent based model of atherogenesis that has been previously validated using clinical data. It is well known that the major risk in atherosclerosis is the persistent high level of low density lipoprotein (LDL) concentration. However, it is not known if short period of high LDL concentration can cause irreversible damage and if reduction of the LDL concentration (either by life style or drug) can drastically or partially reduce the already acquired risk. We simulated four different clinical situations in a large set of virtual patients (200 per clinical scenario). In the first one the patients lifestyle maintains the concentration of LDL in a no risk range. This is the control case simulation. The second case is represented by patients having high level of LDL with a delay to apply appropriate treatments; The third scenario is characterized by patients with high LDL levels treated with specific drugs like statins. Finally we simulated patients that are characterized by several oxidative events (smoke, sedentary life style, assumption of alcoholic drinks and so on so forth) that effective increase the risk of LDL oxidation. Those preliminary results obviously need to be clinically investigated. It is clear, however, that SimAthero has the power to concretely help medical doctors and clinicians in choosing personalized treatments for the prevention of the atherosclerosis damages.

  1. Polyphenols and Oxidative Stress in Atherosclerosis-Related Ischemic Heart Disease and Stroke

    Directory of Open Access Journals (Sweden)

    Yu-Chen Cheng

    2017-01-01

    Full Text Available Good nutrition could maintain health and life. Polyphenols are common nutrient mainly derived from fruits, vegetables, tea, coffee, cocoa, mushrooms, beverages, and traditional medicinal herbs. They are potential substances against oxidative-related diseases, for example, cardiovascular disease, specifically, atherosclerosis-related ischemic heart disease and stroke, which are health and economic problems recognized worldwide. In this study, we reviewed the risk factors for atherosclerosis, including hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette smoking as well as the antioxidative activity of polyphenols, which could prevent the pathology of atherosclerosis, including endothelial dysfunction, low-density lipoprotein oxidation, vascular smooth muscle cell proliferation, inflammatory process by monocytes, macrophages or T lymphocytes, and platelet aggregation. The strong radical-scavenging properties of polyphenols would exhibit antioxidative and anti-inflammation effects. Polyphenols reduce ROS production by inhibiting oxidases, reducing the production of superoxide, inhibiting OxLDL formation, suppressing VSMC proliferation and migration, reducing platelet aggregation, and improving mitochondrial oxidative stress. Polyphenol consumption also inhibits the development of hypertension, diabetes mellitus, hyperlipidemia, and obesity. Despite the numerous in vivo and in vitro studies, more advanced clinical trials are necessary to confirm the efficacy of polyphenols in the treatment of atherosclerosis-related vascular diseases.

  2. Evaluation of carotid intima-media thickness in children with migraine: a marker of subclinical atherosclerosis.

    Science.gov (United States)

    Poyrazoglu, Hatice Gamze; Vurdem, Umit Erkan; Arslan, Alev; Uytun, Salih

    2016-10-01

    Migraine is a commonly seen neurovascular disorder during childhood. Inflammation induced by the activation of cytokines and neuropeptides is implied in its pathophysiology. There is an association between inflammation and atherosclerosis in patients with migraine. In addition, there is a strong correlation between early atherosclerotic wall lesions and carotid intima-media thickness (CIMT). The study population consisted of 57 migraine patients aged 5-17 years, as well as 47 healthy children who served as the control group. Those migraine patients who were not receiving any medications at the interictal period were compared to healthy controls in terms of their measured lipid levels, thyroid function, vitamin B12 levels, serum iron levels, iron binding capacity, complete blood count, C-reactive protein (CRP) levels, and carotid intima-media thickness (CIMT) scores, which may comprise risk factors for atherosclerosis. When children in the migraine and control groups were compared in terms of those risk factors that are known to be related to vascular changes, no significant differences were found. However, a significant difference was detected in CIMT values (P < 0.05). Atherosclerosis commences in childhood, and there is a long period of time before the onset of ischemic symptoms occurs. In children with migraine, an evaluation of CIMT can be used as a non-invasive imaging modality to detect atherosclerosis, which develops in the context of chronic inflammation. In this way, measures to reduce morbidity and mortality, which may result from cardiovascular diseases, can be implemented.

  3. Citrullus lanatus `Sentinel' (Watermelon) Extract Reduces Atherosclerosis in LDL Receptor Deficient Mice

    Science.gov (United States)

    Poduri, Aruna; Rateri, Debra L.; Saha, Shubin K.; Saha, Sibu; Daugherty, Alan

    2012-01-01

    Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar `sentinel', on hypercholesterolemia-induced atherosclerosis in mice. Male LDL receptor deficient mice at 8 weeks old were given either C. lanatus `sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water, while fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus `sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus `sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake, and urine output between the two groups. C. lanatus `sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate/low density lipoprotein cholesterol. Plasma concentrations of MCP-1 and IFN-γ were decreased and IL-10 increased in mice consuming C. lanatus `sentinel' extract. Intake of C. lanatus `sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus `sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. PMID:22902326

  4. Development of soil water regime under spruce stands

    Directory of Open Access Journals (Sweden)

    Tužinský Ladislav

    2017-06-01

    Full Text Available The aim of this paper is to analyse the water regime of soils under spruce ecosystems in relation to long-lasting humid and drought periods in the growing seasons 1991-2013. The dominant interval humidity in observing growing seasons is semiuvidic interval with soil moisture between hydro-limits maximal capillary capacity (MCC and point of diminished availability (PDA. Gravitationally seepage concentrated from accumulated winter season, water from melting snow and existing atmospheric precipitation occurs in the soil only at the beginning of the growing season. The supplies of soil water are significantly decreasing in the warm climate and precipitant deficient days. The greatest danger from drought threatens Norway spruce during the summer months and it depends on the duration of dry days, water supply at the beginning of the dry days, air temperature and the intensity of evapotranspiration. In the surface layers of the soil, with the maximum occurrence of active roots, the water in semiarid interval area between hydro-limits PDA and wilting point (WP decreases during the summer months. In the culminating phase occurs the drying to moisture state with capillary stationary and the insufficient supply of available water for the plants. Physiological weakening of Norway spruce caused by set of outlay components of the water balance is partially reduced by delivering of water by capillary action from deeper horizons. In extremely dry periods, soil moisture is decreasing also throughout the soil profile (0-100 cm into the bottom third of the variation margin hydro-limits MCC-PDA in the category of capillary less moving and for plants of low supply of usable water (60-90 mm. The issue of deteriorated health state of spruce ecosystems is considered to be actual. Changes and developments of hydropedological conditions which interfere the mountain forests represent the increasing danger of the drought for the spruce.

  5. Institutional paradoxes of vat under developing economy of transition period

    Directory of Open Access Journals (Sweden)

    Dmitriy G. Bachurin

    2016-01-01

    Full Text Available Objective to determine the characteristics of the destructive impact of VAT taxation on the socioeconomic situation of the Russian Federation. Methods the research is based on the complex economic and legal methodology including the institutional approach with the account of the national socioeconomic and legal realities determining the conditions of functioning of branches and particular enterprises in the Russian economy. Results the conditions and characteristics of the introduction of VAT in the Russian Federation are viewed the reasons are revealed for the formation and development of the problemcausing VAT in the domestic tax system the socioeconomic implications of VAT are analyzed the viability of replacing VAT for a turnover tax is demonstrated. Scientific novelty for the first time the conceptual position is articulated that under the realities of the reformed Russian economy the normativelegal outline of the VAT complements the accumulated destructive potential blocking the way to the industrial growth in the national economy enhances the asymmetry of conditions of different forms of ownership while the actual conditions of the transition period in Russia do not correspond to the main idea and purpose of VAT as an institution aimed at the efficient relocation of a significant part of the newly created value added to the social sectors and at the modernizing effect on the productive forces for technological improvement in industry. Practical significance the provisions and conclusions of the article can be used when discussing issues on the need for the VAT reform in the Russian Federation including switching to the turnover tax. nbsp

  6. A Genome-wide Trans-ethnic Interaction Study Links the PIGR-FCAMR Locus to Coronary Atherosclerosis Via Interactions Between Genetic Variants and Residential Exposure to Traffic

    Science.gov (United States)

    Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic air pollution is a ubiquitous source of air pollution in developed nations, and is associated with multiple cardiovascular outcomes such as: coronary atherosclerosis, peripheral ar...

  7. Mechanism underlying the development of unilateral spatial neglect

    International Nuclear Information System (INIS)

    Nishikiori, Etsuko

    1992-01-01

    To test the hypothesis that functional disturbance of the neural network involving the inferior parietal lobule (IPL), anterior cingulate gyrus (ACG), dorsolateral frontal lobe (DLF), and thalamus (TH) as components of the right hemisphere underlies the development of unilateral spatial neglect (USN), cerebral perfusion was measured by 123 I-IMP SPECT in 32 patients with cerebrovascular right brain damage, 20 of whom had USN and 12 of whom did not. In analyzing the SPECT data, RI uptake in the four component regions and cerebellum (serving as a control) were estimated by symmetrically placing 'regions of interest' from both hemispheres on SPECT slices, most suitable for each region. The 'regional to cerebellar ratio' (R/CE ratio) for each component region was calculated and the values were compared. In the USN group, R/CE ratio values for each component region in the right hemisphere were significantly lower than those in the left, whereas in the non-USN group there was no right-left difference. When R/CE ratio values for each component region in the right hemisphere were compared between the USN and non-USN group, those for the IPL, ACG and TH were significantly lower in the USN group; the value for the DLF was also lower in the USN group, although the difference was not significant. Significantly lower values of R/CE for each component region in the right hemisphere were noticed when the regions showed apparent involvement on X-ray CT/MRI. Furthermore, in seven of the USN patients where lesions revealed by CT/MRI did not involve network components, the R/CE ratio values for the components in the right hemisphere were lower than those in the left; the difference was significant for the IPL, ACG and TH, but not for the DLF. It is suggested that functional disturbance of the neural network involving the IPL, ACG, DLF and TH in the right hemisphere might underlie the development of USN. (author)

  8. Apolipoprotein E and carotid artery atherosclerosis - The Rotterdam study

    NARCIS (Netherlands)

    Slooter, AJC; Bots, ML; Havekes, LM; del Sol, AI; Cruts, M; Grobbee, DE; Hofman, A; Van Broeckhoven, C; Witteman, JCM; van Duijn, CM

    Background and Purpose-Carotid artery atherosclerosis is a strong predictor for future stroke. It is yet unclear whether the apolipoprotein E polymorphism (APOE) is related to atherosclerosis in the carotid arteries. The aim of the present study was to investigate the role of APOE in carotid artery

  9. Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis

    DEFF Research Database (Denmark)

    Ye, Yu-Xiang; Calcagno, Claudia; Binderup, Tina

    2015-01-01

    tomography-computed tomography imaging of cell proliferation in atherosclerosis. METHODS AND RESULTS: (18)F-FLT positron emission tomography-computed tomography was performed in mice, rabbits, and humans with atherosclerosis. In apolipoprotein E knock out mice, increased (18)F-FLT signal was observed...

  10. Is there an association between coronary atherosclerosis and ...

    African Journals Online (AJOL)

    Background: Atherosclerotic disease is the most common cause of death in the United States and prostate cancer has the highest incidence among males in the United States. Reports have indicated that atherosclerosis and cancers my share common pathoetiologic and pathogenetic cascades. If atherosclerosis and ...

  11. [Optimization of organizational approaches to management of patients with atherosclerosis].

    Science.gov (United States)

    Barbarash, L S; Barbarash, O L; Artamonova, G V; Sumin, A N

    2014-01-01

    Despite undoubted achievements of modern cardiology in prevention and treatment of atherosclerosis, cardiologists, neurologists, and vascular surgeons are still facing severe stenotic atherosclerotic lesions in different vascular regions, both symptomatic and asymptomatic. As a rule hemodynamically significant stenoses of different locations are found after development of acute vascular events. In this regard, active detection of arterial stenoses localized in different areas just at primary contact of patients presenting with symptoms of ischemia of various locations with care providers appears to be crucial. Further monitoring of these stenoses is also important. The article is dedicated to innovative organizational approaches to provision of healthcare to patients suffering from circulatory system diseases that have contributed to improvement of demographic situation in Kuzbass.

  12. Atherosclerosis of the carotid artery: evaluation by magnetic resonance angiography.

    Science.gov (United States)

    Wildy, K S; Yuan, C; Tsuruda, J S; Ferguson, M S; Wen, N; Subramaniam, D S; Strandness, D E

    1996-01-01

    Carotid artery atherosclerotic plaques (APs) can lead to brain ischemia, an event shown to correlate with both the degree of stenosis and the composition of the AP. Currently, accurate estimates of stenosis can be obtained by either x-ray angiography or three-dimensional time-of-flight (TOF) magnetic resonance angiography (MRA). Our purpose was to determine whether three-dimensional TOF MRA images could also provide information on plaque location, morphology, and composition. Seven pre-endarterectomy patients underwent three-dimensional TOF MRA. After endarterectomy, plaque histology was evaluated. Three-dimensional TOF MRA images contained sufficient soft tissue contrast to differentiate the plaques from the surrounding tissues in all cases. Estimation of plaque morphology had 80% correlation with histology. Finally, intraplaque hemorrhage and calcification were deplicted as regions of moderately high and very low intensity, respectively. These preliminary results suggest that three-dimensional TOF MRA may be useful in studying the development and progression of carotid atherosclerosis.

  13. Mechanisms of foam cell formation in atherosclerosis.

    Science.gov (United States)

    Chistiakov, Dimitry A; Melnichenko, Alexandra A; Myasoedova, Veronika A; Grechko, Andrey V; Orekhov, Alexander N

    2017-11-01

    Low-density lipoprotein (LDL) and cholesterol homeostasis in the peripheral blood is maintained by specialized cells, such as macrophages. Macrophages express a variety of scavenger receptors (SR) that interact with lipoproteins, including SR-A1, CD36, and lectin-like oxLDL receptor-1 (LOX-1). These cells also have several cholesterol transporters, including ATP-binding cassette transporter ABCA1, ABCG1, and SR-BI, that are involved in reverse cholesterol transport. Lipids internalized by phagocytosis are transported to late endosomes/lysosomes, where lysosomal acid lipase (LAL) digests cholesteryl esters releasing free cholesterol. Free cholesterol in turn is processed by acetyl-CoA acetyltransferase (ACAT1), an enzyme that transforms cholesterol to cholesteryl esters. The endoplasmic reticulum serves as a depot for maintaining newly synthesized cholesteryl esters that can be processed by neutral cholesterol ester hydrolase (NCEH), which generates free cholesterol that can exit via cholesterol transporters. In atherosclerosis, pro-inflammatory stimuli upregulate expression of scavenger receptors, especially LOX-1, and downregulate expression of cholesterol transporters. ACAT1 is also increased, while NCEH expression is reduced. This results in deposition of free and esterified cholesterol in macrophages and generation of foam cells. Moreover, other cell types, such as endothelial (ECs) and vascular smooth muscle cells (VSMCs), can also become foam cells. In this review, we discuss known pathways of foam cell formation in atherosclerosis.

  14. Atherosclerosis risk factors in pigeon squabs

    International Nuclear Information System (INIS)

    Klumpp, S.A.; Clarkson, T.B.

    1986-01-01

    The basis for atherosclerosis susceptibility of White Carneau (WC) and resistance of Show Racer (SR) pigeons is not known. Body weight (BW), total serum cholesterol (TSC), growth of the aorta and replication of endothelial cells of the distal thoracic aorta (lesion prone site) of 1, 2 and 4 week old squabs were studied. Aortic measurements were determined morphometrically, and endothelial cell replication was quantitated by 24-hour 3 H-thymidine labeling and whole-mount SEM autoradiography. From hatching to 4 weeks, BW increased more in WC than SR (22 to 473 gm in WC vs 19 to 416 gm in SR, p 2 ) in WC and 44% (101, 140 and 146 mm 2 ) in SR. Aortic surface area was significantly larger (0 = 0.002) in the 4 week WC than 4 week SR. 3 H-thymidine labeled endothelial cells at 1, 2 and 4 weeks were 783, 387 and 53 in WC and 674, 283 and 27 cells/mm 2 in SR. Endothelial replication in the 4 week WC was twice that of the SR and significantly different between breeds at 2 and 4 weeks (p = 0.04; p = 0.02, respectively). Higher TSC, endothelial cell replication and larger aortic surface area in the WC may be contributing factors to increased atherosclerosis susceptibility

  15. Effects of intra-abdominal sepsis on atherosclerosis in mice.

    Science.gov (United States)

    Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C

    2014-09-03

    and vascular cell adhesion molecule 1) and the adhesion assay, a functional measure of endothelial activation, were elevated at 72 hours and 120 hours in mice that underwent CLP versus sham-operations (all at P <0.05). Using a combination of existing murine models for atherosclerosis and sepsis, we found that CLP, a model of intra-abdominal sepsis, accelerates atheroma development. Accelerated atheroma burden was associated with prolonged systemic, endothelial and intimal inflammation and was not explained by ongoing infection. These findings support observations in humans and demonstrate the feasibility of a long-term follow-up murine model of sepsis.

  16. [Correction of lipid peroxidation and antioxidant system disorders by bioflavonoids during modeling of cholesterol atherosclerosis in rabbits].

    Science.gov (United States)

    Shysh, A M; Pashevin, D O; Dosenko, V Ie; Moĭbenko, O O

    2011-01-01

    We have studied the influence of bioflavonoids (quercetin, corvitin) on lipid peroxidation and antioxidant enzymes in the modeling of cholesterol atherosclerosis in rabbits. It has been shown that simultaneous administration of the quercetin derivative corvitin suppressed lipid peroxidation. We showed that under hypercholesterolemia, the concentration of malone dialdehyde in myocardial tissue in rabbits is significantly increased, while administration of bioflavonoids decreased the concentration of malone dialdehyde by 38.3%. Furthermore, corvitin caused activating effects on antioxidant enzymes superoxide dismutase and catalase in cardiac tissue. Our data suggest that bioflavonoids are able to suppress lipid peroxidation and prevent the decrease ofantioxidant enzymes activity in rabbits with cholesterol-rich diet induced atherosclerosis.

  17. [EVALUATION OF ARTERIAL STIFFNESS AND POSSIBILITY TO PREDICT CAROTID ATHEROSCLEROSIS IN PATIENTS WITH ESSENTIAL HYPERTENSION BASED ON AN OUTPATIENT FACILITY].

    Science.gov (United States)

    Polipanov, A G; Mamasaidov, Zh A; Geleskhanova, Yu N; Cheskidova, N B; Romanova, T A; Dzhumagulova, A S

    2016-01-01

    To estimate the possibility of predicting the presence and severity of coronary atherosclerosis from arterial stiffness characteristics and augmentation index (AIx) in patients with essential hypertension (EH) obtained under outpatient conditions. The general clinical examination of 15 patients aged 30-70 yr with EH was supplemented by measuring blood glucose and creatinine levels, the lipid status (LWLP, HDLP, TG), duplex scanning of carotid arteries, and evaluation of arterial stiffness by pulsed wave contour analysis. AIx and age were independent risk factors of coronary atherosclerosis in patients with EH and severity of its manifestations. AIx values over 25% were with high specificity (over 85%) associated with atherosclerotic lesions.

  18. Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis

    Directory of Open Access Journals (Sweden)

    Erdi Sozen

    2014-01-01

    Full Text Available Atherosclerosis and its complications are major causes of death all over the world. One of the major risks of atherosclerosis is hypercholesterolemia. During atherosclerosis, oxidized low density lipoprotein (oxLDL regulates CD36-mediated activation of c-jun amino terminal kinase-1 (JNK1 and modulates matrix metalloproteinase (MMP induction which stimulates inflammation with an invasion of monocytes. Additionally, inhibition of proteasome leads to an accumulation of c-jun and phosphorylated c-jun and activation of activator protein-1 (AP-1 related increase of MMP expression. We have previously reported a significant increase in cluster of differentiation 36 (CD36 mRNA levels in hypercholesterolemic rabbits and shown that vitamin E treatment prevented the cholesterol induced increase in CD36 mRNA expression. In the present study, our aim is to identify the signaling molecules/transcription factors involved in the progression of atherosclerosis following CD36 activation in an in vivo model of hypercholesterolemic (induced by 2% cholesterol containing diet rabbits. In this direction, proteasomal activities by fluorometry and c-jun, phospo c-jun, JNK1, MMP-9 expressions by quantitative RT-PCR and immunoblotting were tested in aortic tissues. The effects of vitamin E on these changes were also investigated in this model. As a result, c-jun was phosphorylated following decreased proteasomal degradation in hypercholesterolemic group. MMP-9 expression was also increased in cholesterol group rabbits contributing to the development of atherosclerosis. In addition, vitamin E showed its effect by decreasing MMP-9 levels and phosphorylation of c-jun.

  19. Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis.

    Science.gov (United States)

    Wang, Pei; Xu, Tian-Ying; Guan, Yun-Feng; Zhao, Yan; Li, Zhi-Yong; Lan, Xiao-Hong; Wang, Xia; Yang, Peng-Yuan; Kang, Zhi-Min; Vanhoutte, Paul M; Miao, Chao-Yu

    2014-06-01

    Endothelial dysfunction is an initial and vascular smooth muscle cell (VSMC) apoptosis, a later step of atherosclerosis. Hypothyroidism accelerates atherosclerosis. However, the early events responsible for this pro-atherosclerotic effect are unclear. Rats were resistant to induction of atherosclerosis by high cholesterol diet alone, but became susceptible in hypothyroid state achieved by administration of propylthiouracil (PTU) for 6 weeks. VSMC dysfunction and apoptosis were obvious within 1 week after PTU treatment, without signs of endothelial dysfunction. This early VSMC damage was caused by hypothyroidism but not the high cholesterol diet. In ApoE knockout mice, PTU-induced hypothyroidism triggered early VSMC apoptosis, increased oxidative stress, and accelerated atherosclerosis development. Thyroid hormone supplementation (T4, 10, or 50 μg/kg) prevented atherogenic phenotypes in hypothyroid rats and mice. In rats, thyroidectomy caused severe hypothyroidism 5 days after operation, which also led to rapid VSMC dysfunction and apoptosis. In vitro studies did not show a direct toxic effect of PTU on VSMCs. In contrast, thyroid hormone (T3, 0.75 μg/L plus T4, 50 nmol/L) exerted a direct protection against VSMC apoptosis, which was reduced by knockdown of TRα1, rather than TRβ1 and TRβ2 receptors. TRα1-mediated inhibition of apoptotic signalling of JNKs and caspase-3 contributed to the anti-apoptotic action of thyroid hormone. These findings provide an in vivo example for VSMC apoptosis as an early trigger of hypothyroidism-associated atherosclerosis, and reveal activation of TRα1 receptors to prevent VSMC apoptosis as a therapeutic strategy in this disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  20. A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Lianxiang Bi

    2017-12-01

    Full Text Available Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate—yet significant—pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

  1. A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis.

    Science.gov (United States)

    Bi, Lianxiang; Wacker, Bradley K; Bueren, Emma; Ham, Ervin; Dronadula, Nagadhara; Dichek, David A

    2017-12-15

    Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate-yet significant-pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

  2. Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center.

    Science.gov (United States)

    Santilli, S; Kast, D R; Grozdev, I; Cao, L; Feig, R L; Golden, J B; Debanne, S M; Gilkeson, R C; Orringer, C E; McCormick, T S; Ward, N L; Cooper, K D; Korman, N J

    2016-07-22

    Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation. We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP. 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders. A tertiary care cohort of psoriasis patients have a high prevalence of early

  3. Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Antoneta Granic

    Full Text Available Elevated low-density lipoprotein (LDL-cholesterol is a risk factor for both Alzheimer's disease (AD and Atherosclerosis (CVD, suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy-in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1 high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis' first prediction, 2 Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3 oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL, induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4 LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5 cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6 ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol's aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol

  4. Atherosclerosis in Watanabe heritable hyperlipidaemic rabbits. Evaluation by macroscopic, microscopic and biochemical methods and comparison of atherosclerosis variables

    DEFF Research Database (Denmark)

    Hansen, B F; Mortensen, A; Hansen, J F

    1994-01-01

    estimation of aortic atherosclerosis extent and by biochemical analysis of aortic cholesterol content. No noteworthy atherosclerosis was demonstrated within 19 months in heterozygous rabbits. In homozygous rabbits, atherosclerotic lesions were seen from the age of 4 months and progressed with age. All 19......-month-old rabbits had severe atherosclerotic disease. As much as 64% of the variation in atherosclerosis extent/severity could be explained by serum cholesterol and age. A highly significant correlation between the various methods for quantitation of atherosclerosis extent and/or severity...... was demonstrated, suggesting that quantitative microscopy, macroscopic morphometry and determination of aortic cholesterol content may be equally valid as a measure of atherosclerosis in WHHL rabbits and are therefore interchangeable....

  5. Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men

    OpenAIRE

    Hisamatsu, Takashi; Miura, Katsuyuki; Arima, Hisatomi; Kadota, Aya; Kadowaki, Sayaka; Torii, Sayuki; Suzuki, Sentaro; Miyagawa, Naoko; Sato, Atsushi; Yamazoe, Masahiro; Fujiyoshi, Akira; Ohkubo, Takayoshi; Yamamoto, Takashi; Murata, Kiyoshi; Abbott, Robert D.

    2016-01-01

    Background Smoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia. Methods and Results In a population?based sample of 1019 Japanese men aged 40 to 79?years, without CVD, we examined cross?sectional associations of smoking status, cumulative pack?years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular ...

  6. Shared Genetic Architecture in the Relationship between Adult Stature and Subclinical Coronary Artery Atherosclerosis

    Science.gov (United States)

    Cassidy-Bushrow, Andrea E.; Bielak, Lawrence F.; Sheedy, Patrick F.; Turner, Stephen T.; Chu, Julia S.; Peyser, Patricia A.

    2011-01-01

    Background Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. Methods 877 asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Results Adult height was significantly and inversely associated with CAC score (P=0.01). After adjusting for age, sex, and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P=0.001) and -1 (P<0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P=0.024). Conclusions Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. PMID:21937044

  7. Developing Library Services for the Nomadic Population under the ...

    African Journals Online (AJOL)

    Basic education in Nigeria under the Universal Basic Education (UBE) Programme provides expanded opportunities to meet the basic learning needs of children, youths and adults in school and out of school. Every library meets the educational and informational needs of an identified community of users by providing ...

  8. Horticultural Exports of Developing Countries: Issues under WTO Regime

    Directory of Open Access Journals (Sweden)

    Deepak Shah

    2008-03-01

    Full Text Available This paper seeks to evaluate the present and future prospects of developing and developed countries in agricultural exports in general and in horticultural exports in particular. The study also evaluates the behaviour of international export prices for agricultural commodities, both for developing and developed nations. In general, this study provides an insight into the direction in which various developed and developing countries are heading for insofar as their agricultural and horticultural exports are concerned in the changed market conditions. The study has made a few major observations. First, the study shows decline in market share of developing countries’ in world agricultural exports in the face of marginal increase in their market share in world fruits and vegetable (F&V exports during the period between 1981 and 1997. Second, although the study shows lower market share of developing countries’ in world F&V exports during the period between 1981 and 1997, the growth in F&V exports as proportion of total agricultural exports is noticed to be much faster for developing countries’ as against the developed countries’ during the same period. Third, though agricultural exports of Least Developed Countries (LDC have grown only marginally between 1981 and 1997, the growth in their F&V exports is seen to have been tremendous, especially after the late eighties period. Similarly, Socialist Countries of Asia (SCA and developing countries of Oceania have also shown sharp increases in their F&V exports after the late eighties period. Fourth, while except America, other Africa and Oceania, all the developing countries have shown decline in their market share in total F&V exports of Developing Market Economies (DME, Asia shows rise in its market share not only in agriculture but also in F&V exports of DME. Another major observation of this study is in terms of instabilities in export prices. The instabilities in export prices of agricultural

  9. Disparities in Under-Five Child Injury Mortality between Developing and Developed Countries: 1990–2013

    Directory of Open Access Journals (Sweden)

    Yun Huang

    2016-07-01

    Full Text Available Objective: Using estimates from the 2013 Global Burden of Disease (GBD study, we update evidence on disparities in under-five child injury mortality between developing and developed countries from 1990 to 2013. Methods: Mortality rates were accessed through the online visualization tool by the GBD study 2013 group. We calculated percent change in child injury mortality rates between 1990 and 2013. Data analysis was conducted separately for <1 year and 1–4 years to specify age differences in rate changes. Results: Between 1990 and 2013, over 3-fold mortality gaps were observed between developing countries and developed countries for both age groups in the study time period. Similar decreases in injury rates were observed for developed and developing countries (<1 year: −50% vs. −50% respectively; 1–4 years: −56% vs. −58%. Differences in injury mortality changes during 1990–2013 between developing and developed nations varied with injury cause. There were greater reductions in mortality from transport injury, falls, poisoning, adverse effects of medical treatment, exposure to forces of nature, and collective violence and legal intervention in developed countries, whereas there were larger decreases in mortality from drowning, exposure to mechanical forces, and animal contact in developing countries. Country-specific analysis showed large variations across countries for both injury mortality and changes in injury mortality between 1990 and 2013. Conclusions: Sustained higher child injury mortality during 1990–2013 for developing countries merits the attention of the global injury prevention community. Countries that have high injury mortality can benefit from the success of other countries.

  10. Methods for the development of large computer codes under LTSS

    International Nuclear Information System (INIS)

    Sicilian, J.M.

    1977-06-01

    TRAC is a large computer code being developed by Group Q-6 for the analysis of the transient thermal hydraulic behavior of light-water nuclear reactors. A system designed to assist the development of TRAC is described. The system consists of a central HYDRA dataset, R6LIB, containing files used in the development of TRAC, and a file maintenance program, HORSE, which facilitates the use of this dataset

  11. Rationale and protocol of a trial for prevention of diabetic atherosclerosis by using antiplatelet drugs: study of Diabetic Atherosclerosis Prevention by Cilostazol (DAPC study

    Directory of Open Access Journals (Sweden)

    Kawamori Ryuzo

    2006-08-01

    Full Text Available Abstract Background Secondary treatment of arteriosclerosis may be applicable for the primary prevention of atherosclerosis in diabetic patients. This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects. Methods Patients with type 2 diabetes and arteriosclerosis obliterans from the Eastern Asian countries were registered online and randomly assigned either to the aspirin group (81–100 mg/day or the cilostazol group (100–200 mg/day in this international, 2-year, prospective follow-up interventional study. Results The primary study endpoint was changes in right and left maximum intima-media thickness of the common carotid artery. Secondary endpoints include changes in right and left maximum intima-media thickness of the internal carotid artery; semiquantitative evaluation of cerebral infarction by magnetic resonance imaging; cardiovascular events including sudden death, stroke, transient cerebral ischemic attacks, acute myocardial infarction, angina, and progression of arteriosclerosis obliterans; overall death; withdrawal; and change in ankle-brachial pressure index. Conclusion This is the first study to use an online system that was developed in Asian countries for pooling data from an international clinical trial. These findings are expected to help in the prevention of diabetic atherosclerosis and subsequent cardiovascular and cerebrovascular disease.

  12. A Diet Pattern with More Dairy and Nuts, but Less Meat Is Related to Lower Risk of Developing Hypertension in Middle-Aged Adults: The Atherosclerosis Risk in Communities (ARIC Study

    Directory of Open Access Journals (Sweden)

    Aaron R. Folsom

    2013-05-01

    Full Text Available Dietary intake among other lifestyle factors influence blood pressure. We examined the associations of an ―a priori‖ diet score with incident high normal blood pressure (HNBP; systolic blood pressure (SBP 120–139 mmHg, or diastolic blood pressure (DBP 80–89 mmHg and no antihypertensive medications and hypertension (SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or taking antihypertensive medication. We used proportional hazards regression to evaluate this score in quintiles (Q and each food group making up the score relative to incident HNBP or hypertension over nine years in the Atherosclerosis Risk of Communities (ARIC study of 9913 African-American and Caucasian adults aged 45–64 years and free of HNBP or hypertension at baseline. Incidence of HNBP varied from 42.5% in white women to 44.1% in black women; and incident hypertension from 26.1% in white women to 40.8% in black women. Adjusting for demographics and CVD risk factors, the ―a priori‖ food score was inversely associated with incident hypertension; but not HNBP. Compared to Q1, the relative hazards of hypertension for the food score Q2–Q5 were 0.97 (0.87–1.09, 0.91 (0.81–1.02, 0.91 (0.80–1.03, and 0.86 (0.75–0.98; ptrend = 0.01. This inverse relation was largely attributable to greater intake of dairy products and nuts, and less meat. These findings support the 2010 Dietary Guidelines to consume more dairy products and nuts, but suggest a reduction in meat intake.

  13. Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications

    Directory of Open Access Journals (Sweden)

    Ambrish Kumar

    2013-06-01

    Full Text Available Ethanol is the main constituent of alcoholic beverages that exerts toxicity to neuronal development. Ethanol affects synaptogenesis and prevents proper brain development. In humans, synaptogenesis takes place during the third trimester of pregnancy, and in rodents this period corresponds to the initial few weeks of postnatal development. In this period neuronal maturation and differentiation begin and neuronal cells start migrating to their ultimate destinations. Although the neuronal development of all areas of the brain is affected, the cerebellum and cerebellar neurons are more susceptible to the damaging effects of ethanol. Ethanol’s harmful effects include neuronal cell death, impaired differentiation, reduction of neuronal numbers, and weakening of neuronal plasticity. Neuronal development requires many hormones and growth factors such as retinoic acid, nerve growth factors, and cytokines. These factors regulate development and differentiation of neurons by acting through various receptors and their signaling pathways. Ethanol exposure during development impairs neuronal signaling mechanisms mediated by the N-methyl-d-aspartate (NMDA receptors, the retinoic acid receptors, and by growth factors such as brain-derived neurotrophic factor (BDNF, insulin-like growth factor 1 (IGF-I, and basic fibroblast growth factor (bFGF. In combination, these ethanol effects disrupt cellular homeostasis, reduce the survival and migration of neurons, and lead to various developmental defects in the brain. Here we review the signaling mechanisms that are required for proper neuronal development, and how these processes are impaired by ethanol resulting in harmful consequences to brain development.

  14. Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients

    Directory of Open Access Journals (Sweden)

    Luciano Alves Matias da Silveira

    Full Text Available Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals with liver cirrhosis, observing macroscopic and microscopic changes in lipid and collagen deposits and in the liver. We also aimed to verify the association of lipid and collagen fiber deposits with gender, age and body mass index, and to relate alcoholism, liver cirrhosis and atherosclerosis. Method: We performed a study based on autopsy reports of patients with alcoholic liver cirrhosis, with analysis of aorta and liver fragments to verify the occurrence and degree of atherosclerosis, as well as collagen contents. Results: Microscopic atherosclerosis was higher in young subjects (early injury and in patients with alcoholic liver cirrhosis. The macroscopic analysis of atherosclerosis in aortas showed that patients in more advanced age groups presented more severe classifications. Atherosclerosis, both micro and macroscopically, and the percentage of fibrosis in the liver and aorta were more expressive in females. Conclusion: Cirrhotic patients presented a higher percentage of fibrosis and lipidosis, and may represent a group susceptible to the accelerated progression of cardiovascular diseases. Investigative studies contribute to targeting health-promoting interventions, reducing the mortality and costs of treating cardiovascular disease.

  15. Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Gabriel G. Dorighello

    2016-01-01

    Full Text Available Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent.

  16. Recent advances in lipoprotein and atherosclerosis: A nutrigenomic approach

    Directory of Open Access Journals (Sweden)

    López, Sergio

    2009-03-01

    Full Text Available Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of atherosclerosis. More intriguingly, it has been demonstrated that the extent to which each lipid or lipoprotein is associated with cardiovascular disease depends on the time to last meal; thus, postprandial lipoproteins, main lipoproteins in blood after a high-fat meal, have been shown to strongly influence atherogenesis. As a complex biological process, the full cellular and molecular characterization of atherosclerosis derived by diet, calls for application of the newly developing “omics” techniques of analysis. This review will considered recent studies using high-throughput technologies and a nutrigenomic approach to reveal the patho-physiological effects that the fasting and postprandial lipoproteins may exert on the vascular wall.La aterosclerosis es una enfermedad en la que múltiples factores, entre los que se encuentra la dieta, contribuyen a la degradación de la pared vascular. En la etiología de la aterogénesis son determinantes las lipoproteínas plasmáticas y los distintos tipos celulares de la pared vascular, incluyendo una respuesta inflamatoria. La ingesta de alimentos afecta la concentración y composición de las lipoproteínas, ejerciendo un papel de riesgo o protector durante las diferentes etapas del proceso aterosclerótico. Es importante destacar que la naturaleza de las lipoproteínas y por lo tanto su papel en la enfermedad cardiovascular, también depende del tiempo transcurrido entre comidas. Por ejemplo, las lipoprote

  17. Similarities between pre-eclampsia and atherosclerosis: a protective effect of physical exercise?

    Science.gov (United States)

    Belo, Luís; Santos-Silva, Alice; Quintanilha, Alexandre; Rebelo, Irene

    2008-01-01

    Pre-eclampsia (PE), a characteristic hypertensive disorder of human pregnancy and a leading cause of maternal and fetal mortality and morbidity worldwide, shares some similarities with atherosclerosis, namely the involvement of oxidative stress and of endothelial dysfunction in their pathophysiologies, the presence of similar typical lesions and of common risk factors. Although it is widely accepted that regular physical exercise protects against cardiovascular events, few studies have addressed the impact of physical activity in reducing PE risk. In this paper, similarities between atherosclerosis and PE, involving pathogenic mechanisms, are described. This paper also reviews the studies performed until now that evaluated the impact of regular physical exercise (prenataly or during pregnancy) in reducing risk of PE. The potential mechanisms underlying physical activity as a prophylactic approach of PE, as observed with cardiovascular diseases, are discussed.

  18. Political Opportunism, Corruption and Under development in Africa ...

    African Journals Online (AJOL)

    Barely fi fty years after many African colonies gained their independence from the Europeans, every effort to develop in the continent has been constrained by the political opportunism and corruption of African leaders. This is happening at a time when many developing nations such as China, Brazil and India are making a ...

  19. Connective tissue diseases and noninvasive evaluation of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ardita G

    2014-06-01

    Full Text Available Giorgio Ardita, Giacomo Failla, Paolo Maria Finocchiaro, Francesco Mugno, Luigi Attanasio, Salvatore Timineri, Michelangelo Maria Di SalvoCardiovascular Department, Angiology Unit, Ferrarotto Hospital, Catania, ItalyAbstract: Connective tissue diseases (CTDs are associated with increased risk of cardiovascular disease due to accelerated atherosclerosis. In patients with autoimmune disorders, in addition to traditional risk factors, an immune-mediated inflammatory process of the vasculature seems to contribute to atherogenesis. Several pathogenetic mechanisms have been proposed, including chronic inflammation and immunologic abnormalities, both able to produce vascular damage. Macrovascular atherosclerosis can be noninvasively evaluated by ultrasound measurement of carotid or femoral plaque. Subclinical atherosclerosis can be evaluated by well-established noninvasive techniques which rely on ultrasound detection of carotid intima-media thickness. Flow-mediated vasodilatation and arterial stiffness are considered markers of endothelial dysfunction and subclinical atherosclerosis, respectively, and have been recently found to be impaired early in a wide spectrum of autoimmune diseases. Carotid intima-media thickness turns out to be a leading marker of subclinical atherosclerosis, and many studies recognize its role as a predictor of future vascular events, both in non-CTD individuals and in CTD patients. In rheumatic diseases, flow-mediated dilatation and arterial stiffness prove to be strongly correlated with inflammation, disease damage index, and with subclinical atherosclerosis, although their prognostic role has not yet been conclusively shown. Systemic lupus erythematosus, rheumatoid arthritis, and likely antiphospholipid syndrome are better associated with premature and accelerated atherosclerosis. Inconclusive results were reported in systemic sclerosis.Keywords: rheumatic disease, subclinical atherosclerosis, arterial stiffness

  20. Increased activity of vascular adenosine deaminase in atherosclerosis and therapeutic potential of its inhibition.

    Science.gov (United States)

    Kutryb-Zajac, Barbara; Mateuszuk, Lukasz; Zukowska, Paulina; Jasztal, Agnieszka; Zabielska, Magdalena A; Toczek, Marta; Jablonska, Patrycja; Zakrzewska, Agnieszka; Sitek, Barbara; Rogowski, Jan; Lango, Romuald; Slominska, Ewa M; Chlopicki, Stefan; Smolenski, Ryszard T

    2016-11-01

    Extracellular nucleotides and adenosine that are formed or degraded by membrane-bound ecto-enzymes could affect atherosclerosis by regulating the inflammation and thrombosis. This study aimed to evaluate a relation between ecto-enzymes that convert extracellular adenosine triphosphate to adenine dinucleotide phosphate, adenosine monophosphate, adenosine, and inosine on the surface of the vessel wall with the severity or progression of experimental and clinical atherosclerosis. Furthermore, we tested whether the inhibition of adenosine deaminase will block the development of experimental atherosclerosis. Vascular activities of ecto-nucleoside triphosphate diphosphohydrolase 1, ecto-5'-nucleotidase, and ecto-adenosine deaminase (eADA) were measured in aortas of apolipoprotein E-/- low density lipoprotein receptor (ApoE-/-LDLR-/-) and wild-type mice as well as in human aortas. Plaques were analysed in the entire aorta, aortic root, and brachiocephalic artery by Oil-Red O and Orcein Martius Scarlet Blue staining and vascular accumulation of macrophages. The cellular location of ecto-enzymes was analysed by immunofluorescence. The effect of eADA inhibition on atherosclerosis progression was studied by a 2-month deoxycoformycin treatment of ApoE-/-LDLR-/- mice. The vascular eADA activity prominently increased in ApoE-/-LDLR-/- mice when compared with wild type already at the age of 1 month and progressed along atherosclerosis development, reaching a 10-fold difference at 10 months. The activity of eADA correlated with atherosclerotic changes in human aortas. High abundance of eADA in atherosclerotic vessels originated from activated endothelial cells and macrophages. There were no changes in ecto-nucleoside triphosphate diphosphohydrolase 1 activity, whereas ecto-5'-nucleotidase was moderately decreased in ApoE-/-LDLR-/- mice. Deoxycoformycin treatment attenuated plaque development in aortic root and brachiocephalic artery of ApoE-/-LDLR-/- mice, suppressed vascular

  1. an under theorised icon in research and curriculum development

    African Journals Online (AJOL)

    This paper reviews participation as an emerging moral imperative in a democratising South Africa. .... The issue developed as an extended theme in environmental education where the ..... as a participatory training business on a global scale.

  2. Distinct Functions of Specialized Dendritic Cell Subsets in Atherosclerosis and the Road Ahead

    Directory of Open Access Journals (Sweden)

    Alma Zernecke

    2014-01-01

    Full Text Available Atherosclerotic vascular disease is modulated by immune mechanisms. Dendritic cells (DCs and T cells are present within atherosclerotic lesions and function as central players in the initiation and modulation of adaptive immune responses. In previous years, we have studied the functional contribution of distinct DC subsets in disease development, namely, that of CCL17-expressing DCs as well as that of plasmacytoid DCs that play specialized roles in disease development. This review focuses on important findings gathered in these studies and dissects the multifaceted contribution of CCL17-expressing DCs and pDCs to the pathogenesis of atherosclerosis. Furthermore, an outlook on future challenges faced when studying DCs in this detrimental disease are provided, and hurdles that will need to be overcome in order to enable a better understanding of the contribution of DCs to atherogenesis are discussed, a prerequisite for their therapeutic targeting in atherosclerosis.

  3. MicroRNAs and atherosclerosis: new actors for an old movie.

    Science.gov (United States)

    Santovito, D; Mezzetti, A; Cipollone, F

    2012-11-01

    To date, cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality worldwide. MicroRNAs (miRNAs) are endogenous, short, non-coding RNA sequences able to regulate gene expression principally at the post-transcriptional level. Initially, they were thought to be involved only in developmental timing of worms. Their involvement in human biology was recently discovered and many studies have been performed to demonstrate the role of miRNA in human cancer. Since the first observation in 2005 of their implication in cardiac biology, many studies have demonstrated their role in the genetic modulation of cardiovascular development and in cardiovascular diseases such as cardial remodeling and heart failure, cardiac arrhythmias, cardiac ischaemia, cardiac fibrosis, atherosclerosis and stroke. Thus, the aim of this review is to describe the role of miRNA in atherosclerosis development and evolution and to individuate their role as potential therapeutic target. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Green Product Development with Consumer Heterogeneity under Horizontal Competition

    Directory of Open Access Journals (Sweden)

    Bing Xu

    2018-06-01

    Full Text Available In this paper, we explore the pricing and greenness issues of two competitive firms without and with consumer heterogeneity. We derive and compare the optimal solutions and profits employed by firms under different scenarios. Then, we identify the effects of consumer heterogeneity under different competition intensities. The analytical results reveal that if market competition is at a relatively low level, we find that: (i when the greenness sensitivity of consumers with no preference is sufficiently small, more consumers have high environmental awareness, and companies easily achieve their environmental goals as well as economic goals; (ii when the greenness sensitivity of consumers with no preference is at a medium level, as the fraction of consumers with high environmental awareness increases, and the firm might achieve economic goals at the cost of reducing environmental goals; and (iii when the greenness sensitivity of consumers with no preference is at a high level, the fraction of consumers with high environmental awareness increases, but firms might have more difficulty achieving their environmental and economic goals. On the other hand, if the market competition is at a relatively high level, the presence of consumer heterogeneity can help improve environmental goals, but make achievement of economic goals difficult.

  5. Technologies using accelerator-driven targets under development at BNL

    International Nuclear Information System (INIS)

    Van Tuyle, G.J.

    1994-01-01

    Recent development work conducted at Brookhaven National Laboratory on technologies which use particle accelerator-driven targets is summarized. These efforts include development of the Spallation-Induced Lithium Conversion (SILC) Target for the Accelerator Production of Tritium (APT), the Accelerator-Driven Assembly for Plutonium Transformation (ADAPT) Target for the Accelerator-Based Conversion (ABC) of excess weapons plutonium. The PHOENIX Concept for the accelerator-driven transmutation of minor actinides and fission products from the waste stream of commercial nuclear power plants, and other potential applications

  6. HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Mark S Borja

    Full Text Available High density lipoprotein (HDL cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.

  7. Human thrombomodulin knock-in mice reveal differential effects of human thrombomodulin on thrombosis and atherosclerosis.

    Science.gov (United States)

    Raife, Thomas J; Dwyre, Denis M; Stevens, Jeff W; Erger, Rochelle A; Leo, Lorie; Wilson, Katina M; Fernández, Jose A; Wilder, Jennifer; Kim, Hyung-Suk; Griffin, John H; Maeda, Nobuyo; Lentz, Steven R

    2011-11-01

    We sought to develop a murine model to examine the antithrombotic and antiinflammatory functions of human thrombomodulin in vivo. Knock-in mice that express human thrombomodulin from the murine thrombomodulin gene locus were generated. Compared with wild-type mice, human thrombomodulin knock-in mice exhibited decreased protein C activation in the aorta (Pknock-in mice compared with wild-type mice (Pknock-in mice (12±3 minutes) than in wild-type mice (31±6 minutes; Pknock-in and wild-type mice after injection of endotoxin. When crossed with apolipoprotein E-deficient mice and fed a Western diet, knock-in mice had a further decrease in protein C activation but did not exhibit increased atherosclerosis. Expression of human thrombomodulin in place of murine thrombomodulin produces viable mice with a prothrombotic phenotype but unaltered responses to systemic inflammatory or atherogenic stimuli. This humanized animal model will be useful for investigating the function of human thrombomodulin under pathophysiological conditions in vivo.

  8. Testing of newly developed functional surfaces under pure sliding conditions

    DEFF Research Database (Denmark)

    Godi, Alessandro; Mohaghegh, Kamran; Grønbæk, J.

    2013-01-01

    the surfaces in an industrial context. In this paper, a number of experimental tests were performed using a novel test rig, called axial sliding test, simulating the contact of surfaces under pure sliding conditions. The aim of the experiments is to evaluate the frictional behavior of a new typology...... of textured surfaces, the so-called multifunctional surfaces, characterized by a plateau area able to bear loads and a deterministic pattern of lubricant pockets. Six surface typologies, namely three multifunctional and three machined using classical processes, were chosen to slide against a mirror....... The results comparison showed clearly how employing multifunctional surfaces can reduce friction forces up to 50 % at high normal loads compared to regularly ground or turned surfaces. Friction coefficients approximately equal to 0.12 were found for classically machined surfaces, whereas the values were 0...

  9. Flexural Cracks Development in Reinforced Concrete Beams Under ...

    African Journals Online (AJOL)

    This work attempts to describe the stress-strain state of beams which is gradually changing with the number of load cycles applied and, especially, to analyses formation and development of cracks which greatly affect the whole behaviour of the beams. The method of assessment of maximum cracks' width giving good ...

  10. Unnoticed Ways in which Migration Reinforces Under development ...

    African Journals Online (AJOL)

    But this paper argues that there are unnoticed ways in which migration negatively affects development and low income economies. For this paper, the relationship between ... But to see that migration in turn reinforces underdevelopment, one needs to engage in some complex analysis. Alarmingly, the end-result of the ...

  11. Energy imbalance underlying the development of childhood obesity

    Science.gov (United States)

    The objective of this study was to develop a model based on empirical data and human energetics to predict the total energy cost of weight gain and obligatory increase in energy intake and/or decrease in physical activity level associated with weight gain in children and adolescents. One-year change...

  12. Trade Liberalization and Developing Countries under the Doha Round

    NARCIS (Netherlands)

    J.F. François (Joseph); H. van Meijl; F. van Tongeren

    2003-01-01

    textabstractWe explore the impact of multilateral liberalization, with emphasis on distributional effects across countries. We first develop a realistic "base1ine" that takes into account events such as the entry of China into the WTO and the enlargement of the EU, allowing us to focus on those

  13. Medan City: Development and governance under the decentralisation era

    NARCIS (Netherlands)

    Tarigan, A.K.M.; Samsura, D.A.A.; Sagala, S.; Pencawan, A.V.M.

    2017-01-01

    Over the last 30 years, Medan's economy has grown rapidly and has been the driver of the regional development in North Sumatra Province as well as the northern part of the Sumatra region. The recent adoption of decentralised public policies in Indonesia has to some extent influenced urban

  14. Intracranial angioplasty and stenting for cerebral atherosclerosis: new treatments for stroke are needed.

    Energy Technology Data Exchange (ETDEWEB)

    Higashida, Randall T. [San Francisco Medical Center, Division of Interventional Neurovascular Radiology, University of California, San Francisco, CA (United States); Meyers, Philip M. [Columbia University, The Neurological Institute, New York Presbyterian Hospitals, College of Physicians and Surgeons, New York, NY (United States)

    2006-06-15

    Intracranial atherosclerosis is a common cause of stroke. Recent technological developments offer improved methods for endovascular revascularization of symptomatic and asymptomatic cerebral artery stenosis. Identification of appropriate patients remains a diagnostic challenge, and our knowledge about the natural history of the disease remains limited. At this time, patients with significant intracranial stenosis should receive counseling on the benefits and risks of revascularization therapy. Ultimately, determination of which patients should undergo revascularization procedures will require carefully planned, randomized clinical trials. (orig.)

  15. Intracranial angioplasty and stenting for cerebral atherosclerosis: new treatments for stroke are needed

    International Nuclear Information System (INIS)

    Higashida, Randall T.; Meyers, Philip M.

    2006-01-01

    Intracranial atherosclerosis is a common cause of stroke. Recent technological developments offer improved methods for endovascular revascularization of symptomatic and asymptomatic cerebral artery stenosis. Identification of appropriate patients remains a diagnostic challenge, and our knowledge about the natural history of the disease remains limited. At this time, patients with significant intracranial stenosis should receive counseling on the benefits and risks of revascularization therapy. Ultimately, determination of which patients should undergo revascularization procedures will require carefully planned, randomized clinical trials. (orig.)

  16. Gugulipid causes hypercholesterolemia leading to endothelial dysfunction, increased atherosclerosis, and premature death by ischemic heart disease in male mice.

    Directory of Open Access Journals (Sweden)

    Andrea Leiva

    Full Text Available For proper cholesterol metabolism, normal expression and function of scavenger receptor class B type I (SR-BI, a high-density lipoprotein (HDL receptor, is required. Among the factors that regulate overall cholesterol homeostasis and HDL metabolism, the nuclear farnesoid X receptor plays an important role. Guggulsterone, a bioactive compound present in the natural product gugulipid, is an antagonist of this receptor. This natural product is widely used globally as a natural lipid-lowering agent, although its anti-atherogenic cardiovascular benefit in animal models or humans is unknown. The aim of this study was to determine the effects of gugulipid on cholesterol homeostasis and development of mild and severe atherosclerosis in male mice. For this purpose, we evaluated the impact of gugulipid treatment on liver histology, plasma lipoprotein cholesterol, endothelial function, and development of atherosclerosis and/or ischemic heart disease in wild-type mice; apolipoprotein E knockout mice, a model of atherosclerosis without ischemic complications; and SR-B1 knockout and atherogenic-diet-fed apolipoprotein E hypomorphic (SR-BI KO/ApoER61h/h mice, a model of lethal ischemic heart disease due to severe atherosclerosis. Gugulipid administration was associated with histological abnormalities in liver, increased alanine aminotransferase levels, lower hepatic SR-BI content, hypercholesterolemia due to increased HDL cholesterol levels, endothelial dysfunction, enhanced atherosclerosis, and accelerated death in animals with severe ischemic heart disease. In conclusion, our data show important adverse effects of gugulipid intake on HDL metabolism and atherosclerosis in male mice, suggesting potential and unknown deleterious effects on cardiovascular health in humans. In addition, these findings reemphasize the need for rigorous preclinical and clinical studies to provide guidance on the consumption of natural products and regulation of their use in the

  17. [Development of a prediabetic state under chronic alcohol intoxication].

    Science.gov (United States)

    Voĭtenko, V V; Konopel'niuk, V V; Savchuk, O M; Ostapchenko, L I

    2013-01-01

    We investigated the changes in key parameters of carbohydrate and lipid metabolism, which correspond to the clinical picture that accompanies the development of prediabetic condition on the background of chronic alcohol intoxication. From the analysis of glycemic curves obtained during the insulin-glucose test, a speed of glucose uptake by peripheral tissues increased at the 1st day (1.5 fold) and the third day (1.3 fold) of administration of alcohol solution. At the later periods, at 7 and 11 days of ethanol administration, a decreased rate of glucose uptake in animals with chronic alcohol intoxication was detected. We also detected an increased content of serotonin in the blood serum and a decreased (1.2 fold) serotonin content in rat brain during the whole period of development of chronic alcohol intoxication.

  18. Developing human health exposure scenarios for petroleum substances under REACH

    Energy Technology Data Exchange (ETDEWEB)

    Carter, M.; De Wilde, P.; Maksimainen, K.; Margary, A.; Money, C.; Pizzella, G.; Svanehav, T.; Tsang, W.; Urbanus, J.; Rohde, A.

    2012-12-15

    This report describes the approaches that were adopted by CONCAWE to prepare the human exposure estimates in the chemical safety assessments of the REACH registration dossiers for petroleum substances based on all applicable regulatory guidance. Separate exposure estimates were developed for workers and for consumers and included inhalation and dermal routes. The complex nature of petroleum substances required various scientifically justified refinements of the regulatory guidance.

  19. Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development

    OpenAIRE

    Anna P. Durbin; Stephen S. Whitehead

    2011-01-01

    Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Past...

  20. Development of Virtual Environment under Member State Support Program

    International Nuclear Information System (INIS)

    Koh, Byungmarn; Lee, Nayoung

    2013-01-01

    Member State Support Program (MSSP) is comprised of various programs such as development of safeguards approach, training, information analysis and so on. Each support programs would be evaluated biennially through coordinators' meeting. IAEA publish 'Development and Implementation Support Programme for Nuclear Verification' so that the member state can review it. In the program, IAEA specify the need to develop the virtual reality based training tools. The objective of this project is to develop comprehensive training software dedicated to verification activities in the field based on the virtual environment. The training for the IAEA inspector is indispensable to maintain or improve their verification capability and to be prepared for the inspection of the complicated facilities. However, the grabbing of the available facility is not easy due to following limitations such as security, confidentiality, interference of the commercial operation and so on. Therefore, the virtual environment, which can replace a real facility, is required for the IAEA training. The objective of this software is to support the IAEA's verification capability. It is useful for the trainer and trainee to better understand how nuclear materials are processed in the fuel fabrication facility and what kind safeguards approaches are needed at each process before inspections. The final product will be integrated in the IAEA safeguards training courses to improve the efficiency of the safeguards training. Also we are going to make a decision if additional projects such as CANDU fuel parts or other facilities depending on evaluation results at the IAEA training course will be held on Korea in this year

  1. Development of Virtual Environment under Member State Support Program

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Byungmarn; Lee, Nayoung [Korea Institute of Nuclear Non-proliferation and Control, Daejeon (Korea, Republic of)

    2013-05-15

    Member State Support Program (MSSP) is comprised of various programs such as development of safeguards approach, training, information analysis and so on. Each support programs would be evaluated biennially through coordinators' meeting. IAEA publish 'Development and Implementation Support Programme for Nuclear Verification' so that the member state can review it. In the program, IAEA specify the need to develop the virtual reality based training tools. The objective of this project is to develop comprehensive training software dedicated to verification activities in the field based on the virtual environment. The training for the IAEA inspector is indispensable to maintain or improve their verification capability and to be prepared for the inspection of the complicated facilities. However, the grabbing of the available facility is not easy due to following limitations such as security, confidentiality, interference of the commercial operation and so on. Therefore, the virtual environment, which can replace a real facility, is required for the IAEA training. The objective of this software is to support the IAEA's verification capability. It is useful for the trainer and trainee to better understand how nuclear materials are processed in the fuel fabrication facility and what kind safeguards approaches are needed at each process before inspections. The final product will be integrated in the IAEA safeguards training courses to improve the efficiency of the safeguards training. Also we are going to make a decision if additional projects such as CANDU fuel parts or other facilities depending on evaluation results at the IAEA training course will be held on Korea in this year.

  2. On transform coding tools under development for VP10

    Science.gov (United States)

    Parker, Sarah; Chen, Yue; Han, Jingning; Liu, Zoe; Mukherjee, Debargha; Su, Hui; Wang, Yongzhe; Bankoski, Jim; Li, Shunyao

    2016-09-01

    Google started the WebM Project in 2010 to develop open source, royaltyfree video codecs designed specifically for media on the Web. The second generation codec released by the WebM project, VP9, is currently served by YouTube, and enjoys billions of views per day. Realizing the need for even greater compression efficiency to cope with the growing demand for video on the web, the WebM team embarked on an ambitious project to develop a next edition codec, VP10, that achieves at least a generational improvement in coding efficiency over VP9. Starting from VP9, a set of new experimental coding tools have already been added to VP10 to achieve decent coding gains. Subsequently, Google joined a consortium of major tech companies called the Alliance for Open Media to jointly develop a new codec AV1. As a result, the VP10 effort is largely expected to merge with AV1. In this paper, we focus primarily on new tools in VP10 that improve coding of the prediction residue using transform coding techniques. Specifically, we describe tools that increase the flexibility of available transforms, allowing the codec to handle a more diverse range or residue structures. Results are presented on a standard test set.

  3. Accelerated atherosclerosis in patients with systemic autoimmune diseases

    NARCIS (Netherlands)

    De Leeuw, K.; Kallenberg, Cees; Bijl, Marc; Shoenfeld, Y.; Gershwin, M.E.; Shoenfeld, Y; Gershwin, ME

    2005-01-01

    Systemic autoimmune diseases such as systemic lupus erythematosus and Wegener's granulomatosis are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared with age- and sex-matched controls. Many risk factors are involved in the pathogenesis of atherosclerosis,

  4. Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yavuz Beyazit

    2011-01-01

    Full Text Available Local hematopoietic bone marrow (BM renin-angiotensin system (RAS affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II, the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R, has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

  5. (18)F-FDG PET imaging of murine atherosclerosis

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Pedersen, Sune Folke; Christoffersen, Christina

    2012-01-01

    To study whether (18)F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between (18)F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE(-/-) mice....

  6. Extracranial cerebral arterial atherosclerosis in Iranian patients suffering ischemic strokes

    Directory of Open Access Journals (Sweden)

    Sayed Ali Mousavi

    2006-12-01

    Full Text Available BACKGROUND: To determine the distribution and severity of extracranial carotid arterial atherosclerosis in Iranian patients with ischemic stroke. METHODS: 328 patients with ischemic stroke were included in this study. Doppler ultrasound was used for evaluation of atherosclerosis in extracranial carotid arteries. The NASCET criteria were used to measure carotid stenosis. RESULTS: Ninety of 328 patients (27.4% were found to have atherosclerotic plaques; 40 of these patients were women and 50 were men. Sixty-eight patients (20.7% had artery stenosis <50%, 13 patients (3.95% had 50-70 % artery stenosis and 6 (1.8% had >70% artery stenosis. CONCLUSIONS: Extracranial atherosclerosis is not rare in Iranian patients with ischemic stroke, but most carotid artery lesions were plaques with <50% stenosis. KEY WORDS: Atherosclerosis, ischemic stroke, carotid stenosis.

  7. Intelligent systems in oil field development under uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Pacheco, Marco A.C.; Vellasco, Marley M.B.R. (eds.) [PUC-Rio, Rio de Janeiro (Brazil). Dept. of Electrical Engineering

    2009-07-01

    Intelligent Systems use a range of methodologies for analysis, pre-processing, storage, organization, enhancing and mining of operational data, turning it into useful information and knowledge for decision makers in business enterprises. These intelligent technologies for decision support have been used with success by companies and organizations that are looking for competitive advantages whenever the issues on forecast, optimization, risks analysis, fraud detection, and decision under uncertainties are presented. Intelligent Systems (IS) offer to managers and decision makers the best solutions for complex applications, normally considered difficult, very restrictive or even impossible. The use of such techniques leads to a revolutionary process which has a significant impact in the business management strategy, by providing on time, correct information, ready to use. Computational intelligence techniques, especially genetic algorithms, genetic programming, neural networks, fuzzy logic and neuro-fuzzy as well as modern finance theories, such as real options theory, are here presented and exemplified in oil and gas exploitation and production. This book is addressed to executives and students, directly involved or interested in intelligent management in different fields. (orig.)

  8. Recent advances in lipoprotein and atherosclerosis: A nutrigenomic approach

    OpenAIRE

    López, Sergio; Ortega, Almudena; Varela, Lourdes; Bermúdez, Beatriz; Muriana, Francisco JG; Abia, Rocío

    2009-01-01

    Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of a...

  9. Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients

    OpenAIRE

    Silveira, Luciano Alves Matias da; Torquato, Bianca Gonçalves Silva; Oliveira, Mariana Silva; Juliano, Guilherme Ribeiro; Oliveira, Lívia Ferreira; Cavellani, Camila Lourencini; Ramalho, Luciana Santos; Espindula, Ana Paula; Teixeira, Vicente de Paula Antunes; Ferraz, Mara Lúcia Fonseca

    2017-01-01

    Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals ...

  10. Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis.

    Science.gov (United States)

    Ma, Xiaojuan; Feng, Yingmei

    2016-07-19

    As the pathological basis of cardiovascular disease (CVD), atherosclerosis is featured as a chronic inflammation. Hypercholesterolemia is an independent risk factor for CVD. Accumulated studies have shown that hypercholesterolemia is associated with myeloid cell expansion, which stimulates innate and adaptive immune responses, strengthens inflammation, and accelerates atherosclerosis progression. Hematopoietic stem/progenitor cells (HSPC) in bone marrow (BM) expresses a panel of lipoprotein receptors to control cholesterol homeostasis. Deficiency of these receptors abrogates cellular cholesterol efflux, resulting in HSPC proliferation and differentiation in hypercholesterolemic mice. Reduction of the cholesterol level in the lipid rafts by infusion of reconstituted high-density lipoprotein (HDL) or its major apolipoprotein, apoA-I, reverses hypercholesterolemia-induced HSPC expansion. Apart from impaired cholesterol metabolism, inhibition of reactive oxygen species production suppresses HSPC activation and leukocytosis. These data indicate that the mechanisms underlying the effects of hypercholesterolemia on HSPC proliferation and differentiation could be multifaceted. Furthermore, dyslipidemia also regulates HSPC-neighboring cells, resulting in HSPC mobilization. In the article, we review how hypercholesterolemia evokes HSPC activation and mobilization directly or via its modification of BM microenvironment. We hope this review will bring light to finding key molecules to control HSPC expansion, inflammation, and atherosclerosis for the treatment of CVD.

  11. Bilateral Ischemic Optic Neuropathy Developed under Interferon Therapy

    Directory of Open Access Journals (Sweden)

    Fatih Selcukbiricik

    2012-01-01

    Full Text Available Introduction. Interferon is a glycoprotein produced by assigned cells of immune system. It has been used in many different diseases. Although flu-like syndrome, myalgia, rash, hypotension, thrombocytopenia and peripheral neuropathy due to interferon use are encountered frequently, ocular side effects are rare, generally mild and transient. Case Report. 47-year-old female patient, presented with a mass lesion in right renal pelvis. Right radical nephrectomy was applied and the histopathological examination was consistent with papillary renal cell carcinoma. Interferon alpha treatment was started subcutaneously at the dose of 5 MIU/3 times in a week. Four weeks after the interferon therapy, suddenly bilateral visual loss developed. We discussed the diagnosis, followup, and treatment of the patient who developed irreversible ischemic optic neuropathy and had no previous known primary systemic disease to cause this condition. Conclusion. We suggest that patients should be screened for risk factors causing optic ischemic neuropathy, before interferon therapy. Although there was no adequate information in the literature for the followup, patients should be monitorized before, 1 month after, and 2 months after the treatment. And if there is no complication, we suggest that they should be followed up at 3-month intervals.

  12. Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development

    Directory of Open Access Journals (Sweden)

    Anna P. Durbin

    2011-09-01

    Full Text Available Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.

  13. Next-generation dengue vaccines: novel strategies currently under development.

    Science.gov (United States)

    Durbin, Anna P; Whitehead, Stephen S

    2011-10-01

    Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.

  14. Shielding Flowers Developing under Stress: Translating Theory to Field Application

    Directory of Open Access Journals (Sweden)

    Noam Chayut

    2014-07-01

    Full Text Available Developing reproductive organs within a flower are sensitive to environmental stress. A higher incidence of environmental stress during this stage of a crop plants’ developmental cycle will lead to major breaches in food security. Clearly, we need to understand this sensitivity and try and overcome it, by agricultural practices and/or the breeding of more tolerant cultivars. Although passion fruit vines initiate flowers all year round, flower primordia abort during warm summers. This restricts the season of fruit production in regions with warm summers. Previously, using controlled chambers, stages in flower development that are sensitive to heat were identified. Based on genetic analysis and physiological experiments in controlled environments, gibberellin activity appeared to be a possible point of horticultural intervention. Here, we aimed to shield flowers of a commercial cultivar from end of summer conditions, thus allowing fruit production in new seasons. We conducted experiments over three years in different settings, and our findings consistently show that a single application of an inhibitor of gibberellin biosynthesis to vines in mid-August can cause precocious flowering of ~2–4 weeks, leading to earlier fruit production of ~1 month. In this case, knowledge obtained on phenology, environmental constraints and genetic variation, allowed us to reach a practical solution.

  15. Hippocampal-neocortical functional reorganization underlies children's cognitive development.

    Science.gov (United States)

    Qin, Shaozheng; Cho, Soohyun; Chen, Tianwen; Rosenberg-Lee, Miriam; Geary, David C; Menon, Vinod

    2014-09-01

    The importance of the hippocampal system for rapid learning and memory is well recognized, but its contributions to a cardinal feature of children's cognitive development-the transition from procedure-based to memory-based problem-solving strategies-are unknown. Here we show that the hippocampal system is pivotal to this strategic transition. Longitudinal functional magnetic resonance imaging (fMRI) in 7-9-year-old children revealed that the transition from use of counting to memory-based retrieval parallels increased hippocampal and decreased prefrontal-parietal engagement during arithmetic problem solving. Longitudinal improvements in retrieval-strategy use were predicted by increased hippocampal-neocortical functional connectivity. Beyond childhood, retrieval-strategy use continued to improve through adolescence into adulthood and was associated with decreased activation but more stable interproblem representations in the hippocampus. Our findings provide insights into the dynamic role of the hippocampus in the maturation of memory-based problem solving and establish a critical link between hippocampal-neocortical reorganization and children's cognitive development.

  16. Reverse association of omega-3/omega-6 polyunsaturated fatty acids ratios with carotid atherosclerosis in patients on hemodialysis.

    Science.gov (United States)

    Umemoto, Norio; Ishii, Hideki; Kamoi, Daisuke; Aoyama, Toru; Sakakibara, Takashi; Takahashi, Hiroshi; Tanaka, Akihito; Yasuda, Yoshinari; Suzuki, Susumu; Matsubara, Tatsuaki; Murohara, Toyoaki

    2016-06-01

    Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are widely recognized to have beneficial effects against cardiovascular disease. We investigated the association of n-3 PUFAs levels with carotid atherosclerosis in patients on hemodialysis (HD), who are at high risk for cardiovascular events. Carotid ultra-sound was performed in a total of 461 patients on HD (male 67%, age 67 ± 12years, diabetes rate 46%). Intima-media thickness (IMT) and the plaque score (PS) in carotid arteries were measured. Carotid atherosclerosis was defined as IMT >1.2 mm and/or PS > 5.0. The levels of n-6 PUFAs [dihomo-gamma-linolenic acid (DHLA) and arachidonic acid (AA)] and n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] were also measured prior to carotid ultra-sound. Carotid atherosclerosis was observed in 94 patients (20.4%). Individual PUFAs levels were comparable between patients with and without carotid atherosclerosis. However, the ratio of EPA/AA and that of n-3/n-6 PUFAs were significantly lower in patients with carotid atherosclerosis compared to those without (median 0.36 vs. 0.41, p = 0.031 and 0.85 vs. 0.93, p = 0.041, respectively]. After adjustment for other confounders, the ratio of EPA/AA (OR 0.30, 95% CI 0.12-0.70, p = 0.0055) and the ratio of n-3/n-6 PUFAs (OR 0.45, 95% CI 0.25-0.80, p = 0.0066) showed an independent reverse association with carotid atherosclerosis. In addition, the area under receiver-operating characteristic curves for carotid atherosclerosis was significantly greater in an established risk model with EPA/AA and n-3/n-6 ratios than in the established risk model alone. These data suggest that low ratios of both EPA/AA ratio and n-3/n-6 PUFAs were closely associated with carotid atherosclerosis in patients on HD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Multifocal atherosclerosis in patient after acute first degree radiation sickness.

    Directory of Open Access Journals (Sweden)

    Metlyaeva N.A.

    2014-12-01

    Full Text Available Purpose: assessment the heavy psychosomatic and all-somatic cardiovascular and cerebrovascular pathology of patient, transferred an acute I degree radiation sickness, from the general evenly gamma-beta radiation. Conclusions. The subdepressive and disturbing-depressive syndrome of patient, transferred an acute radiation sickness (ARS of I degree, from the general evenly gamma-beta radiation, was independent risk factor of development of multifocal atherosclerosis; Features of development of all-somatic and psychosomatic pathology of patient are based on a combination of genetic prerequisites, environment influences (the stress caused by accident on the ChNPP and social factors, influencing on him during a course of life, especially during early socialization. Thus at development of psychosomatic frustration the combination of feature of the mental reaction connected with the personal characteristic and special relationship between mental (stress and physiological (somatic by aspects of reaction which led to metabolism violation, to aging, decrease in adaptation opportunities of an organism and development age — dependent pathology took place.

  18. Association of Television Viewing Time with Body Composition and Calcified Subclinical Atherosclerosis in Singapore Chinese.

    Directory of Open Access Journals (Sweden)

    Ei Ei Khaing Nang

    Full Text Available Sedentary behavior such as television viewing may be an independent risk factor for coronary heart disease. However, few studies have assessed the impact of television viewing time on coronary artery calcification and it remains unclear how body fat contributes to this relationship. The aim of this study is to evaluate the association between television viewing time and subclinical atherosclerosis and whether effects on visceral or subcutaneous fat may mediate any associations observed.This was a cross-sectional study of 398 Chinese participants (192 men and 206 women from Singapore prospective study. Participants were free from known cardiovascular diseases and underwent interview, health screening, computed tomography scans of coronary arteries and abdomen. Spearman's correlation was used to test the correlation between television viewing time, physical activity, body composition and abdominal fat distribution. The association between television viewing time and subclinical atherosclerosis was assessed by multiple logistic regression analysis.In men, television viewing time was significantly correlated with higher body fat mass index, percent body fat, subcutaneous and visceral fat. These associations were in the same direction, but weaker and not statistically significant in women. Television viewing time (hours/day was associated with subclinical atherosclerosis in men (odds ratio: 1.41, 95% CI: 1.03-1.93 but no significant association was observed in women (odds ratio: 0.88, 95% CI: 0.59-1.31 after adjusting for potential socio-demographic and lifestyle confounders. Further adjustments for biological factors did not affect these associations.Television viewing time was associated with greater adiposity and higher subcutaneous and visceral fat in men. TV viewing time was also associated with subclinical atherosclerosis in men and the potential mechanisms underlying this association require further investigation.

  19. Association of Television Viewing Time with Body Composition and Calcified Subclinical Atherosclerosis in Singapore Chinese.

    Science.gov (United States)

    Nang, Ei Ei Khaing; van Dam, Rob M; Tan, Chuen Seng; Mueller-Riemenschneider, Falk; Lim, Yi Ting; Ong, Kai Zhi; Ee, Siqing; Lee, Jeannette; Tai, E Shyong

    2015-01-01

    Sedentary behavior such as television viewing may be an independent risk factor for coronary heart disease. However, few studies have assessed the impact of television viewing time on coronary artery calcification and it remains unclear how body fat contributes to this relationship. The aim of this study is to evaluate the association between television viewing time and subclinical atherosclerosis and whether effects on visceral or subcutaneous fat may mediate any associations observed. This was a cross-sectional study of 398 Chinese participants (192 men and 206 women) from Singapore prospective study. Participants were free from known cardiovascular diseases and underwent interview, health screening, computed tomography scans of coronary arteries and abdomen. Spearman's correlation was used to test the correlation between television viewing time, physical activity, body composition and abdominal fat distribution. The association between television viewing time and subclinical atherosclerosis was assessed by multiple logistic regression analysis. In men, television viewing time was significantly correlated with higher body fat mass index, percent body fat, subcutaneous and visceral fat. These associations were in the same direction, but weaker and not statistically significant in women. Television viewing time (hours/day) was associated with subclinical atherosclerosis in men (odds ratio: 1.41, 95% CI: 1.03-1.93) but no significant association was observed in women (odds ratio: 0.88, 95% CI: 0.59-1.31) after adjusting for potential socio-demographic and lifestyle confounders. Further adjustments for biological factors did not affect these associations. Television viewing time was associated with greater adiposity and higher subcutaneous and visceral fat in men. TV viewing time was also associated with subclinical atherosclerosis in men and the potential mechanisms underlying this association require further investigation.

  20. Imaging pathobiology of carotid atherosclerosis with ultrasmall superparamagnetic particles of iron oxide: an update.

    Science.gov (United States)

    Sadat, Umar; Usman, Ammara; Gillard, Jonathan H

    2017-07-01

    To provide brief overview of the developments regarding use of ultrasmall superparamagnetic particles of iron oxide in imaging pathobiology of carotid atherosclerosis. MRI is a promising technique capable of providing morphological and functional information about atheromatous plaques. MRI using iron oxide particles, called ultrasmall superparamagnetic iron oxide (USPIO) particles, allows detection of macrophages in atherosclerotic tissue. Ferumoxytol has emerged as a new USPIO agent, which has an excellent safety profile. Based on the macrophage-selective properties of ferumoxytol, there is increasing number of recent reports suggesting its effectiveness to detect pathological inflammation. USPIO particles allow magnetic resonance detection of macrophages in atherosclerotic tissue. Ferumoxytol has emerged as a new USPIO agent, with an excellent safety profile. This has the potential to be used for MRI of the pathobiology of atherosclerosis.

  1. Induction of atherosclerosis in mice and hamsters without germline genetic engineering

    DEFF Research Database (Denmark)

    Bjørklund, Martin Mæng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup

    2014-01-01

    RATIONALE: Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation. OBJECTIVE......: To develop a method for induction of atherosclerosis without germline genetic engineering. METHODS AND RESULTS: Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector...... injection followed by high-fat diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total cholesterol increased rapidly and were maintained at high levels, and after 12 weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic root showed progression of lesions...

  2. Animal models of surgically manipulated flow velocities to study shear stress-induced atherosclerosis.

    Science.gov (United States)

    Winkel, Leah C; Hoogendoorn, Ayla; Xing, Ruoyu; Wentzel, Jolanda J; Van der Heiden, Kim

    2015-07-01

    Atherosclerosis is a chronic inflammatory disease of the arterial tree that develops at predisposed sites, coinciding with locations that are exposed to low or oscillating shear stress. Manipulating flow velocity, and concomitantly shear stress, has proven adequate to promote endothelial activation and subsequent plaque formation in animals. In this article, we will give an overview of the animal models that have been designed to study the causal relationship between shear stress and atherosclerosis by surgically manipulating blood flow velocity profiles. These surgically manipulated models include arteriovenous fistulas, vascular grafts, arterial ligation, and perivascular devices. We review these models of manipulated blood flow velocity from an engineering and biological perspective, focusing on the shear stress profiles they induce and the vascular pathology that is observed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. RSX system development under VAX/VMS compatibility mode

    International Nuclear Information System (INIS)

    Fuka, M.A.

    1983-01-01

    The Control System for the Proton Storage Ring now being built at Los Alamos will use a VAX-11/750 as its main control computer with several LSI-11/23 microprocessors reading and controlling the hardware. The VMS Compatibility Mode makes it possible to use the VAX as a development system for the LSI-11/23 microprocessors running the RSX-11S (stand-alone) operating system. Digital Equipment Corporation (DEC)-supplied software is used to generate the RSX-11S operating system and DECNET-11S network software. We use the VMS editors to create source files, the Macro-11 assembler and the PDP-11 Fortran-77 compiler to generate object code, and the RSX Task Builder to link the executable RSX task image. The RSX task then can be tested to some extent on the VAX before it is down-line loaded to the LSI-11/23 for further testing

  4. Developing Physiologic Models for Emergency Medical Procedures Under Microgravity

    Science.gov (United States)

    Parker, Nigel; O'Quinn, Veronica

    2012-01-01

    Several technological enhancements have been made to METI's commercial Emergency Care Simulator (ECS) with regard to how microgravity affects human physiology. The ECS uses both a software-only lung simulation, and an integrated mannequin lung that uses a physical lung bag for creating chest excursions, and a digital simulation of lung mechanics and gas exchange. METI s patient simulators incorporate models of human physiology that simulate lung and chest wall mechanics, as well as pulmonary gas exchange. Microgravity affects how O2 and CO2 are exchanged in the lungs. Procedures were also developed to take into affect the Glasgow Coma Scale for determining levels of consciousness by varying the ECS eye-blinking function to partially indicate the level of consciousness of the patient. In addition, the ECS was modified to provide various levels of pulses from weak and thready to hyper-dynamic to assist in assessing patient conditions from the femoral, carotid, brachial, and pedal pulse locations.

  5. INITIAL DEVELOPMENT OF AÇAÍ PLANTS UNDER SHADE GRADATION

    Directory of Open Access Journals (Sweden)

    ELEANDRO CANDIDO DAPONT

    2016-01-01

    Full Text Available ABSTRACT In order to evaluate the effect of different levels of shading on açai (Euterpe oleracea Mart. plants development, an experiment was conducted at the nursery of Floresta, Rio Branco, AC. The experiment was arranged in a completely randomized design with six treatments and four replications of 25 plants, set as full sunlight and 18%, 35%, 50%, 70%, and 80% shading. The evaluation occurred 125 days after transplantation and the variables were stem diameter, root length, length of the aerial part, total length, dry matter of root, dry matter of aerial part, and total dry matter. With exception of root length, there was significant difference between treatments for all variables. The production of açai plants should be performed using 40% shading.

  6. Bulgarian clusters under development: Political framework and results

    Directory of Open Access Journals (Sweden)

    Bankova Yovka

    2011-01-01

    Full Text Available The idea of clusters is not new but nowadays clusters are in a highlight again. Through cluster policies the countries aim at raising their national competitiveness. The paper deals with two objectives - discussion and evaluation of the strategic framework for clusters in Bulgaria and an analysis of the state of Bulgarian clusters. The paper presents briefly general issues concerning the national competitiveness and clusters as being one of the possible instruments to achieve a sustainable competitiveness. The practice of the policy in the EU in the field of clusters is the basis for conclusions about the role of the governments. The second part deals with the strategic framework for the cluster initiatives in Bulgaria and with a selection of indicators about the SMEs and clusters in the country. On this basis a conclusion about the development stage of Bulgarian clusters is derived.

  7. Life stress and atherosclerosis: a pathway through unhealthy lifestyle.

    Science.gov (United States)

    Mainous, Arch G; Everett, Charles J; Diaz, Vanessa A; Player, Marty S; Gebregziabher, Mulugeta; Smith, Daniel W

    2010-01-01

    To examine the relationship between a general measure of chronic life stress and atherosclerosis among middle aged adults without clinical cardiovascular disease via pathways through unhealthy lifestyle characteristics. We conducted an analysis of The Multi-Ethnic Study of Atherosclerosis (MESA). The MESA collected in 2000 includes 5,773 participants, aged 45-84. We computed standard regression techniques to examine the relationship between life stress and atherosclerosis as well as path analysis with hypothesized paths from stress to atherosclerosis through unhealthy lifestyle. Our outcome was sub-clinical atherosclerosis measured as presence of coronary artery calcification (CAC). A logistic regression adjusted for potential confounding variables along with the unhealthy lifestyle characteristics of smoking, excessive alcohol use, high caloric intake, sedentary lifestyle, and obesity yielded no significant relationship between chronic life stress (OR 0.93, 95% CI 0.80-1.08) and CAC. However, significant indirect pathways between chronic life stress and CAC through smoking (p = .007), and sedentary lifestyle (p = .03) and caloric intake (.002) through obesity were found. These results suggest that life stress is related to atherosclerosis once paths of unhealthy coping behaviors are considered.

  8. Hepatic JAK2 protects against atherosclerosis through circulating IGF-1.

    Science.gov (United States)

    Sivasubramaniyam, Tharini; Schroer, Stephanie A; Li, Angela; Luk, Cynthia T; Shi, Sally Yu; Besla, Rickvinder; Dodington, David W; Metherel, Adam H; Kitson, Alex P; Brunt, Jara J; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P; Bendeck, Michelle P; Robbins, Clinton S; Woo, Minna

    2017-07-20

    Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2's essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection.

  9. Macrophage Phenotype and Function in Different Stages of Atherosclerosis

    Science.gov (United States)

    Tabas, Ira; Bornfeldt, Karin E.

    2016-01-01

    The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for more than 50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to HDL; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and pro-resolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge. PMID:26892964

  10. Vasostatin-2 inhibits cell proliferation and adhesion in vascular smooth muscle cells, which are associated with the progression of atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Jianghong, E-mail: jianghonghou@163.com [Department of Cardiovascular, Weinan Center Hospital, The Middle of Victory Avenue, Linwei District, Weinan City 714000 (China); Xue, Xiaolin [Department of Cardiovascular, The First Affiliated Hospital, College of Medicine, Xi' an Jiaotong University, Xi' an 710061 (China); Li, Junnong [Department of Cardiovascular, Weinan Center Hospital, The Middle of Victory Avenue, Linwei District, Weinan City 714000 (China)

    2016-01-22

    Recently, the serum expression level of vasostatin-2 was found to be reduced and is being studied as an important indicator to assess the presence and severity of coronary artery disease; the functional properties of vasostatin-2 and its relationship with the development of atherosclerosis remains unclear. In this study, we attempted to detect the expression of vasostatin-2 and its impact on human vascular smooth muscle cells (VSMCs). Quantitative real-time PCR (qRT-PCR) and western blot were used to assess the expression level of vasostatin-2 in VSMCs between those from atherosclerosis and disease-free donors; we found that vasostatin-2 was significantly down-regulated in atherosclerosis patient tissues and cell lines. In addition, the over-expression of vasostatin-2 apparently inhibits cell proliferation and migration in VSMCs. Gain-of-function in vitro experiments further show that vasostatin-2 over-expression significantly inhibits inflammatory cytokines release in VSMCs. In addition, cell adhesion experimental analysis showed that soluble adhesion molecules (sICAM-1, sVCAM-1) had decreased expression when vasostatin-2 was over-expressed in VSMCs. Therefore, our results indicate that vasostatin-2 is an atherosclerosis-related factor that can inhibit cell proliferation, inflammatory response and cell adhesion in VSMCs. Taken together, our results indicate that vasostatin-2 could serve as a potential diagnostic biomarker and therapeutic option for human atherosclerosis in the near future. - Highlights: • Vasostatin-2 levels were down-regulated in atherosclerosis patient tissues and VSMCs. • Ectopic expression of vasostatin-2 directly affects cell proliferation and migration in vitro. • Ectopic expression of vasostatin-2 protein affects pro-inflammatory cytokines release in VSMCs. • Ectopic expression of vasostatin-2 protein affects cell adhesion in VSMCs.

  11. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship – a review of LCAT deficiency

    Directory of Open Access Journals (Sweden)

    Savel J

    2012-06-01

    Full Text Available Julia Savel,1,2 Marianne Lafitte,1 Yann Pucheu,1,3 Vincent Pradeau,1 Antoine Tabarin,2,3 Thierry Couffinhal1,3,41Centre d'Exploration, de Prévention et de Traitement de l'Athérosclérose, Hôpital Cardiologique, 2Service d'endocrinologie, CHU Bordeaux, Université Bordeaux Segalen, Bordeaux, France; 3Université de Bordeaux Adaptation cardiovasculaire à l'ischémie, 4INSERM, Adaptation cardiovasculaire à l'ischémie, U1034, Pessac, FranceAbstract: A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations.Keywords: atherosclerosis, LCAT function

  12. Development of a specific geological mapping software under MAPGIS

    International Nuclear Information System (INIS)

    Zhang Wenkai

    2010-01-01

    The most often used mapping software in geological exploration is MAPGIS system, and related standard is established based on it. The software has more agile functions, except for the following shortages: more parameters to select, difficult to master, different parameters to use for each one, low efficiency. As a result, a specific software is developed for geological mapping by using VC++ on the platform of MAPGIS. According to the standards, toolbars are built for strata, rock, geographic information and materials, etc. By pushing on the buttons, the parameters are selected, and menus of toolbars can be modified to select parameters for each working areas, legends can be sorted automatically. So, the speed can be improved greatly, and the parameters can be identical. The software can complete the transition between Gauss coordinate and longitude-latitude coordinate, drawing points, frames by longitude-latitude, responsible form, plain diagram and profile, etc. The software also improves the way of clipping, topologizing, node catching methods. The application of the software indicates that it can improve the speed of geological mapping greatly, and can improve the standardized level of the final maps. (authors)

  13. Kalanchoe crop development under different levels of irrigation

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    Fátima Cibele Soares

    Full Text Available ABSTRACT Despite its importance in the floriculture sector, irrigation management of kalanchoe is characterized by empiricism, being necessary further studies on the use of water by this crop. Thus, the objective of this study is to analyze the several effects of irrigation levels on the growth of kalanchoe crop conducted in greenhouse in the municipality of Alegrete, state of Rio Grande do Sul. The experiment was conducted in a 7 x 15 m protected environment. The experimental design was completely randomized, with four treatments (irrigation levels corresponding to 40, 60, 80 and 100% of the pot water retention capacity - PC and four repetitions, totaling sixteen plots. The crop cycle was 224 days after transplanting and the applied average depths were: 451.82; 367.38; 282.94; 198.51 mm for treatments: 100; 80; 60 and 40% of PC, respectively. Canopy area and number of leaves per plant were evaluated over the crop cycle. In the end of the cycle, the canopy diameter, number of inflorescences per plant and the number of flowers per plant were evaluated. No significant differences were found only to the canopy area, by the F test. Irrigation water depths between 40 and 70% of the pot capacity were more appropriate for the crop growth in the study region. The cultivar presented the best development at irrigation levels below the maximum vessel water retention capacity, that is, it is resistant to drought.

  14. Conservation planning under uncertainty in urban development and vegetation dynamics

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    Carmel, Yohay

    2018-01-01

    Systematic conservation planning is a framework for optimally locating and prioritizing areas for conservation. An often-noted shortcoming of most conservation planning studies is that they do not address future uncertainty. The selection of protected areas that are intended to ensure the long-term persistence of biodiversity is often based on a snapshot of the current situation, ignoring processes such as climate change. Scenarios, in the sense of being accounts of plausible futures, can be utilized to identify conservation area portfolios that are robust to future uncertainty. We compared three approaches for utilizing scenarios in conservation area selection: considering a full set of scenarios (all-scenarios portfolio), assuming the realization of specific scenarios, and a reference strategy based on the current situation (current distributions portfolio). Our objective was to compare the robustness of these approaches in terms of their relative performance across future scenarios. We focused on breeding bird species in Israel’s Mediterranean region. We simulated urban development and vegetation dynamics scenarios 60 years into the future using DINAMICA-EGO, a cellular-automata simulation model. For each scenario, we mapped the target species’ available habitat distribution, identified conservation priority areas using the site-selection software MARXAN, and constructed conservation area portfolios using the three aforementioned strategies. We then assessed portfolio performance based on the number of species for which representation targets were met in each scenario. The all-scenarios portfolio consistently outperformed the other portfolios, and was more robust to ‘errors’ (e.g., when an assumed specific scenario did not occur). On average, the all-scenarios portfolio achieved representation targets for five additional species compared with the current distributions portfolio (approximately 33 versus 28 species). Our findings highlight the importance

  15. Low Levels of CD36 in Peripheral Blood Monocytes in Subclinical Atherosclerosis in Rheumatoid Arthritis: A Cross-Sectional Study in a Mexican Population

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    Eduardo Gómez-Bañuelos

    2014-01-01

    Full Text Available Patients with rheumatoid arthritis (RA have a higher risk for atherosclerosis. There is no clinical information about scavenger receptor CD36 and the development of subclinical atherosclerosis in patients with RA. The aim of this study was to evaluate the association between membrane expression of CD36 in peripheral blood mononuclear cells (PBMC and carotid intima-media thickness (cIMT in patients with RA. Methods. We included 67 patients with RA from the Rheumatology Department of Hospital Civil “Dr. Juan I. Menchaca,” Guadalajara, Jalisco, Mexico. We evaluated the cIMT, considering subclinical atherosclerosis when >0.6 mm. Since our main objective was to associate the membrane expression of CD36 with subclinical atherosclerosis, other molecules related with cardiovascular risk such as ox-LDL, IL-6, and TNFα were tested. Results. We found low CD36 membrane expression in PBMC from RA patients with subclinical atherosclerosis (P<0.001. CD36 mean fluorescence intensity had negative correlations with cIMT (r = −0.578, P<0.001, ox-LDL (r = −0.427, P = 0.05, TNFα (r = −0.729, P<0.001, and IL-6 (r = −0.822, P<0.001. Conclusion. RA patients with subclinical atherosclerosis showed low membrane expression of CD36 in PBMC and increased serum proinflammatory cytokines. Further studies are needed to clarify the regulation of CD36 in RA.

  16. Nitric oxide bioavailability dysfunction involves in atherosclerosis.

    Science.gov (United States)

    Chen, Jing-Yi; Ye, Zi-Xin; Wang, Xiu-Fen; Chang, Jian; Yang, Mei-Wen; Zhong, Hua-Hua; Hong, Fen-Fang; Yang, Shu-Long

    2018-01-01

    The pathological characteristics of atherosclerosis (AS) include lipid accumulation, fibrosis formation and atherosclerotic plaque produced in artery intima, which leads to vascular sclerosis, lumen stenosis and irritates the ischemic changes of corresponding organs. Endothelial dysfunction was closely associated with AS. Nitric oxide (NO) is a multifunctional signaling molecule involved in the maintenance of metabolic and cardiovascular homeostasis. NO is also a potent endogenous vasodilator and enters for the key processes that suppresses the formation vascular lesion even AS. NO bioavailability indicates the production and utilization of endothelial NO in organisms, its decrease is related to oxidative stress, lipid infiltration, the expressions of some inflammatory factors and the alteration of vascular tone, which plays an important role in endothelial dysfunction. The enhancement of arginase activity and the increase in asymmetric dimethylarginine and hyperhomocysteinemia levels all contribute to AS by intervening NO bioavailability in human beings. Diabetes mellitus, obesity, chronic kidney disease and smoking, etc., also participate in AS by influencing NO bioavailability and NO level. Here, we reviewed the relationship between NO bioavailability and AS according the newest literatures. Copyright © 2017. Published by Elsevier Masson SAS.

  17. Noninvasive Diagnostic Technique in Stenotic Coronary Atherosclerosis

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    A. Yu. Vasilyev

    2005-01-01

    Full Text Available Objective: to determine the sensitivity and specificity of combined stress echocardiography (EchoCG using dipyri-damole and dobutamine in diagnosing and defining the extent of stenotic coronary lesions in coronary heart disease (CHD in a group of critically ill patients who are unable to perform a physical exercise.Materials and methods: the study included 57 male patients with suspected acute coronary syndrome who underwent stress EchoCG using dipyridamole in high doses in combination with dobutamine, as well as coronary angiography.Results: stress EchoCG could bring up to the diagnostic criteria in all the patients, of whom 9 patients were found at coronary angiography to have no coronary lesion, 34 and 14 patients had one- and many-vessel lesions, respectively. The sensitivity and specificity of combined stress EchoCG were significantly higher than those of EchoCG used in the diagnosis of CHD.Conclusion: stress EchoCG using dipyridamole in combination with dobutamine is a highly informative safe noninvasive technique for diagnosing CHD, its helps to identify patients with atypical acute coronary syndrome and to form a group of patients to be subject to urgent coronarography and angiosurgical intervention. The pattern of segmental contractile disorders at the height of exercise during combined stress Echo-CG makes it possible to define the site of stenotic coronary atherosclerosis with 97.3% sensitivity and to diagnose many-vessel lesion with 100% sensitivity and 100%specificity.

  18. Moderate beer consumption does not change early or mature atherosclerosis in mice

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    Blanco-Vaca Francisco

    2004-01-01

    Full Text Available Abstract Background Although the consumption of wine in particular has been associated with a lower risk of atherothrombotic cardiovascular disease, systematic reviews differ as to the relative protective effect of beer, wine and spirits. Two previous studies showed that red wine reduces fatty streak formation (early atherosclerosis but not mature atherosclerosis in apolipoprotein (apo E-deficient (apoE-/- mice. Aim of the study To determine whether a moderate beer intake would affect early and mature atherosclerotic lesion formation using control C57BL/6 and apoE-/- mice, respectively, as models. Methods Control C57BL/6 and apoE-/- mice were randomized to receive either water, ethanol, mild beer, dark beer or ethanol-free beer. The level of beer was designed to approximate the alcohol intake currently believed to be beneficial in reducing human vascular risk. Control C57BL/6 mice were fed a Western diet for 24 weeks, and apoE-/- mice a chow diet for 12 weeks. At the end of the trial period, mice were euthanized and atherosclerotic lesions quantified. Plasma lipid concentrations were also measured. Results The amount of atherosclerosis and average number of lesions in the proximal aortic region did not differ among groups in control C57BL/6 mice (p = 0.32 and p = 0.29, respectively and apoE-/- mice (p = 0.19 and p = 0.59, respectively. No consistent differences were observed in plasma lipid and lipoprotein concentrations among water, ethanol and beer groups. Conclusions Moderate beer consumption does not change the development of early or mature atherosclerosis in mice. Our findings do not support the hypothesis of an anti-atherogenic effect of beer. Other potential protective actions of moderate beer consumption such as plaque stabilization, a reduction in plaque intrinsic thrombogenicity, or a reduction in the systemic propensity to thrombosis, remain to be studied.

  19. MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin.

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    Di Gregoli, Karina; Mohamad Anuar, Nur Najmi; Bianco, Rosaria; White, Stephen J; Newby, Andrew C; George, Sarah J; Johnson, Jason L

    2017-01-06

    Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with many cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm stability are poorly understood. To investigate whether miR-181b regulates tissue inhibitor of metalloproteinase-3 expression and affects atherosclerosis and aneurysms. Here, we demonstrate that miR-181b was overexpressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms and correlated with decreased expression of predicted miR-181b targets, tissue inhibitor of metalloproteinase-3, and elastin. Using the well-characterized mouse atherosclerosis models of Apoe - /- and Ldlr -/- , we observed that in vivo administration of locked nucleic acid anti-miR-181b retarded both the development and the progression of atherosclerotic plaques. Systemic delivery of anti-miR-181b in angiotensin II-infused Apoe -/- and Ldlr -/- mice attenuated aneurysm formation and progression within the ascending, thoracic, and abdominal aorta. Moreover, miR-181b inhibition greatly increased elastin and collagen expression, promoting a fibrotic response and subsequent stabilization of existing plaques and aneurysms. We determined that miR-181b negatively regulates macrophage tissue inhibitor of metalloproteinase-3 expression and vascular smooth muscle cell elastin production, both important factors in maintaining atherosclerotic plaque and aneurysm stability. Validation studies in Timp3 -/- mice confirmed that the beneficial effects afforded by miR-181b inhibition are largely tissue inhibitor of metalloproteinase-3 dependent, while also revealing an additional protective effect through elevating elastin synthesis. Our findings suggest that the management of miR-181b and its target genes provides therapeutic potential for limiting the progression of

  20. Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.

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    Elham Khanicheh

    Full Text Available BACKGROUND/OBJECTIVES: Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1 with contrast enhanced ultrasound (CEU could assess treatment effects on endothelial phenotype in early atherosclerosis. METHODS: Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day. At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM and control microbubbles (MB(Ctr. Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression. RESULTS: Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM in non-treated animals (MB(VCAM 2±0.3 vs MB(Ctr 0.7±0.2, p<0.01, but not in statin-treated animals (MB(VCAM 0.8±0.2 vs MB(Ctr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MB(VCAM signal. CONCLUSIONS: Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.

  1. Citrullus lanatus 'sentinel' (watermelon) extract reduces atherosclerosis in LDL receptor-deficient mice.

    Science.gov (United States)

    Poduri, Aruna; Rateri, Debra L; Saha, Shubin K; Saha, Sibu; Daugherty, Alan

    2013-05-01

    Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar 'sentinel,' on hypercholesterolemia-induced atherosclerosis in mice. Male low-density lipoprotein receptor-deficient mice at 8 weeks old were given either C. lanatus 'sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water while being fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus 'sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus 'sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake and in urine output between the two groups. C. lanatus 'sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate-/low-density lipoprotein cholesterol. Plasma concentrations of monocyte chemoattractant protein-1 and interferon-gamma were decreased and those of interleukin-10 were increased in mice consuming C. lanatus 'sentinel' extract. Intake of C. lanatus 'sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus 'sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Feasibility study on RI biochip Application to detection of risk factors of atherosclerosis

    International Nuclear Information System (INIS)

    Ko, Kyong Cheol; Choi, Mi Hee; Park, Sang Hyun; Cho, Kyung Hyun; Lee, Ki Teak

    2009-01-01

    Microarrays can be used to screen thousands of binding events in a parallel and high throughput fashion and are of major importance in discase diagnosis and drug discovery. The use of radioisotope is conventionally regarded as one of the most sensitive detection methods. Atherosclerosis is a common disorder affecting arterial blood vessels. It happens when fat, cholesterol, and other substances made in the arterial blood vessels form a hard substances called plaque. Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), a phospholipase A 2 enzyme, is used as a marker for cardiac disease. The detection of Lp-PLA 2 was accomplished by using radioactive [ 3 H-acetyl] PAF as a substrate and a feasibility study on RI biochip application to detection of Lp-PLA 2 , a risk factors of atherosclerosis was performed. Inhibitive activity of a native plant extract was also determined by using the RI biochip. It was found to be applicable to a high-throughput screening of inhibitors for developing atherosclerosis therapeutic agents

  3. The role of T and B cells in human atherosclerosis and atherothrombosis.

    Science.gov (United States)

    Ammirati, E; Moroni, F; Magnoni, M; Camici, P G

    2015-02-01

    Far from being merely a passive cholesterol accumulation within the arterial wall, the development of atherosclerosis is currently known to imply both inflammation and immune effector mechanisms. Adaptive immunity has been implicated in the process of disease initiation and progression interwined with traditional cardiovascular risk factors. Although the body of knowledge regarding the correlation between atherosclerosis and immunity in humans is growing rapidly, a relevant proportion of it derives from studies carried out in animal models of cardiovascular disease (CVD). However, while the mouse is a well-suited model, the results obtained therein are not fully transferrable to the human setting due to intrinsic genomic and environmental differences. In the present review, we will discuss mainly human findings, obtained either by examination of post-mortem and surgical atherosclerotic material or through the analysis of the immunological profile of peripheral blood cells. In particular, we will discuss the findings supporting a pro-atherogenic role of T cell subsets, such as effector memory T cells or the potential protective function of regulatory T cells. Recent studies suggest that traditional T cell-driven B2 cell responses appear to be atherogenic, while innate B1 cells appear to exert a protective action through the secretion of naturally occurring antibodies. The insights into the immune pathogenesis of atherosclerosis can provide new targets in the quest for novel therapeutic targets to abate CVD morbidity and mortality. © 2014 British Society for Immunology.

  4. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

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    Heera Ram

    2014-01-01

    Full Text Available Acacia senegal L. (Fabaceae seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil for 15 days. Circulating total cholesterol (TC, HDL-cholesterol (HDL-C, LDL-cholesterol (LDL-C, triglycerides, and VLDL-cholesterol (VLDL-C levels; atherogenic index (AI; cardiac lipid peroxidation (LPO; planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34±0.72 and increased lumen volume (51.65±3.66, administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o. for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics.

  5. Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis Using Bioinformatics Analysis

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    Xiaowen Tan

    2017-01-01

    Full Text Available Background. Coronary artery atherosclerosis is a chronic inflammatory disease. This study aimed to identify the key changes of gene expression between early and advanced carotid atherosclerotic plaque in human. Methods. Gene expression dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO, including 16 advanced and 13 early stage atherosclerotic plaque samples from human carotid. Differentially expressed genes (DEGs were analyzed. Results. 42,450 genes were obtained from the dataset. Top 100 up- and downregulated DEGs were listed. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG identification were performed. The result of functional and pathway enrichment analysis indicted that the immune system process played a critical role in the progression of carotid atherosclerotic plaque. Protein-protein interaction (PPI networks were performed either. Top 10 hub genes were identified from PPI network and top 6 modules were inferred. These genes were mainly involved in chemokine signaling pathway, cell cycle, B cell receptor signaling pathway, focal adhesion, and regulation of actin cytoskeleton. Conclusion. The present study indicated that analysis of DEGs would make a deeper understanding of the molecular mechanisms of atherosclerosis development and they might be used as molecular targets and diagnostic biomarkers for the treatment of atherosclerosis.

  6. Detection of Marek's disease virus DNA in Japanese quail susceptible to atherosclerosis

    International Nuclear Information System (INIS)

    Pyrzak, R.; Shih, J.C.H.

    1986-01-01

    Marek's disease virus (MDV) was demonstrated as an etiological agent which causes atherosclerosis in the chicken. Since herpes viruses are ubiquitous, incidences of viral atherogenesis in humans and other animals were speculated. In this laboratory, the atherosclerosis susceptible (SUS) and resistant (RES) Japanese quail were developed as the animal model for atherosclerosis research. The susceptibility of the animal might be due to an infection of MDV or a related quail herpes virus (QHV). An initial attempt to isolate viruses from quail and an agar gel precipitin test for MDC were not positive. A DNA hybridization technique was used to determine whether the MDC-DNA existed in the quail cell. The gene library of MDV EcoRl DNA fragments was used to prepare the DNA probe, labeled with [ 32 P] by nick translation. Dot hybridizations were carried out by mixing the MDV-DNA probe with DNAs isolated from quail tissues. A high stringent condition was used. From this experiment it was found that the tissues from the SUS quail were hybridization positive, but most of them from RES quail were negative. When aortas were compared, the severe atherosclerotic had a strong hybridization (3-4 cop. of genome/cell) whereas the others hybridized moderately (1 cop./cell). It was concluded that genes from MDV or a QHV indeed existed in Japanese quail

  7. Identification of total reversible cysteine oxidation in an atherosclerosis model using a modified biotin switch assay.

    Science.gov (United States)

    Li, Ru; Huang, Jiqing; Kast, Juergen

    2015-05-01

    Oxidative stress due to the imbalance of reactive oxygen species (ROS) and the resulting reversible cysteine oxidation (CysOX) are involved in the early proatherogenic aspect of atherosclerosis. Given that the corresponding redox signaling pathways are still unclear, a modified biotin switch assay was developed to quantify the reversible CysOX in an atherosclerosis model established by using a monocytic cell line treated with platelet releasate. The accumulation of ROS was observed in the model system and validated in human primary monocytes. Through the application of the modified biotin switch assay, we obtained the first reversible CysOX proteome for this model. A total of 75 peptides, corresponding to 53 proteins, were quantified with oxidative modification. The bioinformatics analysis of these CysOX-containing proteins highlighted biological processes including glycolysis, cytoskeleton arrangement, and redox regulation. Moreover, the reversible oxidation of three glycolysis enzymes was observed using this method, and the regulation influence was verified by an enzyme activity assay. NADPH oxidase (NOX) inhibition treatment, in conjunction with the modified biotin switch method, was used to evaluate the global CysOX status. In conclusion, this versatile modified biotin switch assay provides an approach for the quantification of all reversible CysOX and for the study of redox signaling in atherosclerosis as well as in diseases in other biological systems.

  8. Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis

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    Jun-ichi Kawabe

    2014-01-01

    Full Text Available Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process.

  9. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    Energy Technology Data Exchange (ETDEWEB)

    Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

    2003-09-01

    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

  10. Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by Inhibiting Toll-like Receptor 4 Expression.

    Science.gov (United States)

    Zhang, Shanshan; Zou, Jun; Li, Peiyang; Zheng, Xiumei; Feng, Dan

    2018-01-17

    Toll-like receptor 4 (TLR4) has been reported to play a critical role in the pathogenesis of atherosclerosis, the current study aimed to investigate whether curcumin suppresses atherosclerosis development in ApoE-knockout (ApoE -/- ) mice by inhibiting TLR4 expression. ApoE -/- mice were fed a high-fat diet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Curcumin supplementation significantly reduced TLR4 expression and macrophage infiltration in atherosclerotic plaques. Curcumin also reduced aortic interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression, nuclear factor-κB (NF-κB) activity, and plasma IL-1β, TNF-α, soluble VCAM-1 and ICAM-1 levels. In addition, aortic sinus sections revealed that curcumin treatment reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development. In vitro, curcumin inhibited NF-κB activation in macrophages and reduced TLR4 expression induced by lipopolysaccharide. Our results indicate that curcumin protects against atherosclerosis at least partially by inhibiting TLR4 expression and its related inflammatory reaction.

  11. High prevalence of COPD in atherosclerosis patients

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    Tuleta I

    2017-10-01

    Full Text Available Izabela Tuleta, Tarik Farrag, Laura Busse, Carmen Pizarro, Christian Schaefer, Simon Pingel, Georg Nickenig, Dirk Skowasch, Nadjib Schahab Department of Internal Medicine II – Cardiology, Pulmonology and Angiology, University of Bonn, Bonn, Germany Abstract: Atherosclerosis and COPD are both systemic inflammatory diseases that may influence each other. The aim of the present study was to determine the prevalence of COPD in patients with cerebral and/or peripheral artery disease and to assess factors associated with the presence of COPD. Following the diagnosis of cerebral and/or peripheral artery disease by means of duplex sonography, 166 consecutive patients underwent body plethysmography with capillary blood gas analysis. Thereafter, blood tests with determination of different parameters such as lipid profile, inflammatory and coagulation markers were conducted in remaining 136 patients who fulfilled inclusion criteria of the study. Thirty-six out of 136 patients suffered from COPD, mostly in early stages of the disease. Residual volume indicating emphysema was increased (162.9%±55.9% vs 124.5%±37.0%, p<0.05 and diffusion capacity was decreased (55.1%±19.5% vs 75.3%±18.6%, p<0.05 in COPD patients vs non-COPD group. In capillary blood gas analysis, COPD patients had lower partial pressure of oxygen (70.9±11.5 vs 75.2±11.0 mmHg, p<0.05 and higher partial pressure of carbon dioxide (36.8±7.5 vs 34.4±4.4 mmHg, p<0.05 compared with non-COPD individuals. Presence of COPD was associated with predominance of diabetes mellitus, interleukin-8-related systemic neutrophilic inflammation and anemia. In conclusion, COPD is highly prevalent in patients with atherosclerotic artery disease. Keywords: cerebral artery disease, peripheral artery disease, lung function, capillary blood gas, diabetes mellitus, inflammation, interleukin-8, anemia

  12. Radiation-induced carotid artery atherosclerosis

    International Nuclear Information System (INIS)

    Gujral, Dorothy M.; Chahal, Navtej; Senior, Roxy; Harrington, Kevin J.; Nutting, Christopher M.

    2014-01-01

    Purpose: Carotid arteries frequently receive significant doses of radiation as collateral structures in the treatment of malignant diseases. Vascular injury following treatment may result in carotid artery stenosis (CAS) and increased risk of stroke and transient ischaemic attack (TIA). This systematic review examines the effect of radiotherapy (RT) on the carotid arteries, looking at the incidence of stroke in patients receiving neck radiotherapy. In addition, we consider possible surrogate endpoints such as CAS and carotid intima-medial thickness (CIMT) and summarise the evidence for radiation-induced carotid atherosclerosis. Materials and methods: From 853 references, 34 articles met the criteria for inclusion in this systematic review. These papers described 9 studies investigating the incidence of stroke/TIA in irradiated patients, 11 looking at CAS, and 14 examining CIMT. Results: The majority of studies utilised suboptimally-matched controls for each endpoint. The relative risk of stroke in irradiated patients ranged from 1.12 in patients with breast cancer to 5.6 in patients treated for head and neck cancer. The prevalence of CAS was increased by 16–55%, with the more modest increase seen in a study using matched controls. CIMT was increased in irradiated carotid arteries by 18–40%. Only two matched-control studies demonstrated a significant increase in CIMT of 36% and 22% (p = 0.003 and <0.001, respectively). Early prospective data demonstrated a significant increase in CIMT in irradiated arteries at 1 and 2 years after RT (p < 0.001 and <0.01, respectively). Conclusions: The incidence of stroke was significantly increased in patients receiving RT to the neck. There was a consistent difference in CAS and CIMT between irradiated and unirradiated carotid arteries. Future studies should optimise control groups

  13. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  14. Frequency of Subclinical Atherosclerosis in Brazilian HIV-Infected Patients.

    Science.gov (United States)

    Salmazo, Péricles Sidnei; Bazan, Silméia Garcia Zanati; Shiraishi, Flávio Gobbis; Bazan, Rodrigo; Okoshi, Katashi; Hueb, João Carlos

    2018-04-09

    AIDS as well as atherosclerosis are important public health problems. The longer survival among HIV-infected is associated with increased number of cardiovascular events in this population, and this association is not fully understood. To identify the frequency of subclinical atherosclerosis in HIV-infected patients compared to control subjects; to analyze associations between atherosclerosis and clinical and laboratory variables, cardiovascular risk factors, and the Framingham coronary heart disease risk score (FCRS). Prospective cross-sectional case-control study assessing the presence of subclinical atherosclerosis in 264 HIV-infected patients and 279 controls. Clinical evaluation included ultrasound examination of the carotid arteries, arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), laboratory analysis of peripheral blood, and cardiovascular risk according to FCRS criteria. The significance level adopted in the statistical analysis was p media thickness was higher in the HIV group than in controls (p media thickness, was not associated with carotid plaque frequency, and did not alter the mechanical characteristics of the arterial system (PWV and AIx). HIV-infected patients are at increased risk of atherosclerosis in association with classical cardiovascular risk factors. Treatment with protease inhibitors does not promote functional changes in the arteries, and shows no association with increased frequency of atherosclerotic plaques in carotid arteries. The FCRS may be inappropriate for this population.

  15. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    International Nuclear Information System (INIS)

    Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

    2016-01-01

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  16. Osteoprotegerin as a Marker of Atherosclerosis in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Areti Augoulea

    2013-01-01

    Full Text Available Atherosclerosis is the principal cause of cardiovascular disease (CVD and has many risk factors, among which is diabetes. Osteoprotegerin (OPG is a soluble glycoprotein, involved in bone metabolism. OPG is also found in other tissues, and studies have shown that it is expressed in vascular smooth muscle cells. OPG has been implicated in various inflammations and also has been linked to diabetes mellitus. Increased serum OPG levels were found in patients with diabetes and poor glycemic control. Furthermore, prepubertal children with type 1 diabetes have significantly increased OPG levels. Receptor activator of nuclear factor kappa-B ligand (RANKL is not found in the vasculature in normal conditions, but may appear in calcifying areas. OPG and RANKL are important regulators of mineral metabolism in both bone and vascular tissues. Few data are available on the relationship between plasma OPG/RANKL levels and endothelial dysfunction as assessed using noninvasive methods like ultrasound indexes, neither in the general population nor, more specifically, in diabetic patients. The aim of our review study was to investigate, based on the existing data, these interrelationships in order to identify a means of predicting, via noninvasive methods, later development of endothelial dysfunction and vascular complications in diabetic patients.

  17. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

    Science.gov (United States)

    Sanchez-Gaytan, Brenda L; Fay, Francois; Lobatto, Mark E; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E M; van Rijs, Sarian M; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A; Mulder, Willem J M

    2015-03-18

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers.

  18. Qualifying codes under software quality assurance: Two examples as guidelines for codes that are existing or under development

    Energy Technology Data Exchange (ETDEWEB)

    Mangold, D.

    1993-05-01

    Software quality assurance is an area of concem for DOE, EPA, and other agencies due to the poor quality of software and its documentation they have received in the past. This report briefly summarizes the software development concepts and terminology increasingly employed by these agencies and provides a workable approach to scientific programming under the new requirements. Following this is a practical description of how to qualify a simulation code, based on a software QA plan that has been reviewed and officially accepted by DOE/OCRWM. Two codes have recently been baselined and qualified, so that they can be officially used for QA Level 1 work under the DOE/OCRWM QA requirements. One of them was baselined and qualified within one week. The first of the codes was the multi-phase multi-component flow code TOUGH version 1, an already existing code, and the other was a geochemistry transport code STATEQ that was under development The way to accomplish qualification for both types of codes is summarized in an easy-to-follow step-by step fashion to illustrate how to baseline and qualify such codes through a relatively painless procedure.

  19. Qualifying codes under software quality assurance: Two examples as guidelines for codes that are existing or under development

    International Nuclear Information System (INIS)

    Mangold, D.

    1993-05-01

    Software quality assurance is an area of concern for DOE, EPA, and other agencies due to the poor quality of software and its documentation they have received in the past. This report briefly summarizes the software development concepts and terminology increasingly employed by these agencies and provides a workable approach to scientific programming under the new requirements. Following this is a practical description of how to qualify a simulation code, based on a software QA plan that has been reviewed and officially accepted by DOE/OCRWM. Two codes have recently been baselined and qualified, so that they can be officially used for QA Level 1 work under the DOE/OCRWM QA requirements. One of them was baselined and qualified within one week. The first of the codes was the multi-phase multi-component flow code TOUGH version 1, an already existing code, and the other was a geochemistry transport code STATEQ that was under development The way to accomplish qualification for both types of codes is summarized in an easy-to-follow step-by step fashion to illustrate how to baseline and qualify such codes through a relatively painless procedure

  20. Insulin decreases atherosclerosis by inducing endothelin receptor B expression

    DEFF Research Database (Denmark)

    Park, Kyoungmin; Mima, Akira; Li, Qian

    2016-01-01

    Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1...... induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca(2+)]. Using the mice with knockin mutation of eNOS, which had Ser1176 mutated to alanine (AKI), deleting the only known mechanism for insulin to activate eNOS/NO pathway, we observed that IRS1...... overexpression in the endothelia of Aki/ApoE(-/-) mice significantly decreased atherosclerosis. Interestingly, endothelial EDNRB expression was selectively reduced in intima of arteries from diabetic patients and rodents. However, endothelial EDNRB expression was upregulated by insulin via P13K/Akt pathway...

  1. Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis

    International Nuclear Information System (INIS)

    Qiao, Wang; Chaoshu, Tang; Hongfang, Jin; Junbao, Du

    2010-01-01

    Atherosclerosis is a chronic, complex, and progressive pathological process in large and medium sized arteries. The exact mechanism of this process remains unclear. Hydrogen sulfide (H 2 S), a novel gasotransmitter, was confirmed as playing a major role in the pathogenesis of many cardiovascular diseases. It plays a role in vascular smooth muscle cell (VSMC) proliferation and apoptosis, participates in the progress of hyperhomocysteinemia (HHCY), inhibits atherogenic modification of LDL, interferes with vascular calcification, intervenes with platelet function, and there are interactions between H 2 S and inflammatory processes. The role of H 2 S in atherosclerotic pathogenesis highlights the mysteries of atherosclerosis and inspires the search for innovative therapeutic strategies. Here, we review the studies to date that have considered the role of H 2 S in atherosclerosis.

  2. Circumflex coronary artery with aberrant origin and atherosclerosis

    International Nuclear Information System (INIS)

    Ozcan, E.; Bozlar, U.; Celik, T.; Tasar, M.

    2012-01-01

    Full text: Introduction: Circumflex (Cx) coronary artery congenital anomaly is reported to be less than 1% incidence. Coronary arteries with aberrant origin are more likely to have atherosclerosis according to some published literatures. Objectives and tasks: In this study we aim to present computed tomography (CT) angiography findings of a patient, who has Cx artery with aberrant origin and atherosclerotic. Materials and methods: 57-year-old woman without any symptoms who has risk factors to atherosclerosis was referred to our clinic for coronary CT angiography. Results: In CT angiography; we detected Cx coronary artery with aberrant origin (right sinus of valsalva) and retroaortic course. Also we saw intimal irregularities and calcified plaque causing severe narrowing in the proximal segment of artery. Right coronary and left anterior descendant arteries had mild atherosclerosis. Conclusion: Coroner CT angiography, which allows multiplanar imaging with high resolution, is an effective diagnostic tool for coronary artery disease, like not only congenital anomalies but also acquired atherosclerotic disease

  3. Arterial scleroproteins in atherosclerosis and hypertension (Experimental studies)

    International Nuclear Information System (INIS)

    Yurukova, Ts.; Georgiev, P.

    1979-01-01

    The authors studied the neosynthesis of fiber protein (scleroproteins) in the aorta of rats with genetic hypertension and with experimental atherosclerosis following application of 3 H-proline and 3 H-lysine and subsequent determination of radioactivity of the collagen and elastic fractions of the aortic wall. There was a great increase in incorporation of labelled collagen and elastin precursors in the aorta of hypertensive and atherosclerotic animals, in comparison with the control rats - a manifestation of incresed ''de novo'' synthesis of fiber proteins in rats with these arterial diseases. Furthermore, the increased collagenosis dominated over that of elastogenesis. The irregular activation of the biosynthesis of both scleroproteins in hypertensive rats and in rats with atherosclerosis caused remodelling of the macromolecular structure of the arterial wall with predominance of collagen over the remaining hypertension components and progression of atherosclerosis. (author) (author)

  4. Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

    NARCIS (Netherlands)

    Haan, W. de; Vries-van der Weij, J. de; Hoorn, J.W.A. van der; Gautier, T.; Hoogt, C.C. van der; Westerterp, M.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Princen, H.M.G.; Rensen, P.C.N.

    2008-01-01

    BACKGROUND - Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even

  5. Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

    NARCIS (Netherlands)

    de Haan, Willeke; de Vries-van der Weij, Jitske; van der Hoorn, José W. A.; Gautier, Thomas; van der Hoogt, Caroline C.; Westerterp, Marit; Romijn, Johannes A.; Jukema, J. Wouter; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

    2008-01-01

    Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even increased

  6. A pilot study into measurements of markers of atherosclerosis in periodontitis

    NARCIS (Netherlands)

    Leivadaros, E; van der Velden, U; Bizzarro, S; ten Heggeler, JMAG; Gerdes, VEA; Hoek, FJ; Nagy, TOM; Scholma, J; Bakker, SJL; Gans, ROB; ten Cate, H; Loos, BG

    Background: Periodontitis may be a possible risk factor for atherosclerosis. The current pilot study explored arterial wall thickness and other variables associated with atherosclerosis in healthy subjects with and without periodontitis. Methods: Patients with moderate (N = 34) and severe

  7. Non-proinflammatory and responsive nanoplatforms for targeted treatment of atherosclerosis.

    Science.gov (United States)

    Dou, Yin; Chen, Yue; Zhang, Xiangjun; Xu, Xiaoqiu; Chen, Yidan; Guo, Jiawei; Zhang, Dinglin; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

    2017-10-01

    Atherosclerosis is the leading cause of many fatal cardiovascular and cerebrovascular diseases. Whereas nanomedicines are promising for targeted therapy of atherosclerosis, great challenges remain in development of effective, safe, and translational nanotherapies for its treatment. Herein we hypothesize that non-proinflammatory nanomaterials sensitive to low pH or high reactive oxygen species (ROS) may serve as effective platforms for triggerable delivery of anti-atherosclerotic therapeutics in cellular and tissue microenvironments of inflammation. To demonstrate this hypothesis, an acid-labile material of acetalated β-cyclodextrin (β-CD) (Ac-bCD) and a ROS-sensitive β-CD material (Ox-bCD) were separately synthesized by chemical modification of β-CD, which were formed into responsive nanoparticles (NPs). Ac-bCD NP was rapidly hydrolyzed in mildly acidic buffers, while hydrolysis of Ox-bCD NP was selectively accelerated by H 2 O 2 . Using an anti-atherosclerotic drug rapamycin (RAP), we found stimuli-responsive release of therapeutic molecules from Ac-bCD and Ox-bCD nanotherapies. Compared with non-responsive poly(lactide-co-glycolide) (PLGA)-based NP, Ac-bCD and Ox-bCD NPs showed negligible inflammatory responses in vitro and in vivo. By endocytosis in cells and intracellularly releasing cargo molecules in macrophages, responsive nanotherapies effectively inhibited macrophage proliferation and suppressed foam cell formation. After intraperitoneal (i.p.) delivery in apolipoprotein E-deficient (ApoE -/- ) mice, fluorescence imaging showed accumulation of NPs in atherosclerotic plaques. Flow cytometry analysis indicated that the lymphatic translocation mediated by neutrophils and monocytes/macrophages may contribute to atherosclerosis targeting of i.p. administered NPs, in addition to targeting via the leaky blood vessels. Correspondingly, i.p. treatment with different nanotherapies afforded desirable efficacies. Particularly, both pH and ROS

  8. Rate of atherosclerosis progression in ApoE-/- mice long after discontinuation of cola beverage drinking.

    Directory of Open Access Journals (Sweden)

    Matilde Otero-Losada

    Full Text Available This study was conducted in order to evaluate the effect of cola beverages drinking on atherosclerosisand test the hypothesis whether cola beverages consumption at early life stages might affect the development and progression of atherosclerosis later in life. ApoE-/- C57BL/6J mice (8 week-old were randomized in 3 groups (n = 20 each according to free accessto water (W, sucrose sweetened carbonated cola drink(C or aspartame-acesulfame K sweetened carbonated 'light' cola drink (Lfor the next 8 weeks. Drinking treatment was ended by switching C and L groups to drinking water. Four mice per group and time were sequentially euthanized: before treatment (8 weeks-old, at the end of treatment (16 weeks-old and after treatment discontinuation (20 weeks-old, 24 weeks-old, 30 week-old mice. Aortic roots and livers were harvested, processed for histology and serial cross-sections were stained. Aortic plaque area was analyzed and plaque/media-ratio was calculated. Early consumption of cola drinks accelerated atherosclerotic plaque progression favoring the interaction between macrophages and myofibroblasts, without the participation of either T lymphocytes or proliferative activity. Plaque/media-ratio varied according to drink treatment (F2,54 = 3.433, p<0.04 and mice age (F4,54 = 5.009, p<0.03 and was higher in C and L groups compared with age-matched W group (p<0.05 at 16 weeks and 20 weeks, p<0.01 at 24 weeks and 30 weeks. Natural evolution of atherosclerosis in ApoE-/- mice (W group evidenced atherosclerosis acceleration in parallel with a rapid increase in liver inflammation around the 20 weeks of age. Cola drinking within the 8-16 weeks of age accelerated atherosclerosis progression in ApoE-/- mice favoring aortic plaque enlargement (inward remodeling over media thinning all over the study time. Data suggest that cola drinking at early life stages may predispose to atherosclerosis progression later in life in ApoE-/- mice.

  9. Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) study

    KAUST Repository

    Hä gg, Sara; Skogsberg, Josefin; Lundströ m, Jesper; Noori, Peri; Nilsson, Roland; Zhong, Hua; Maleki, Shohreh; Shang, Ming-Mei; Brinne, Bjö rn; Bradshaw, Maria; Bajic, Vladimir B.; Samnegå rd, Ann; Silveira, Angela; Kaplan, Lee M.; Gigante, Bruna; Leander, Karin; de Faire, Ulf; Rosfors, Stefan; Lockowandt, Ulf; Liska, Jan; Konrad, Peter; Takolander, Rabbe; Franco-Cereceda, Anders; Schadt, Eric E.; Ivert, Torbjö rn; Hamsten, Anders; Tegné r, Jesper; Bjö rkegren, Johan

    2009-01-01

    of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two

  10. Increased YKL-40 expression in patients with carotid atherosclerosis

    DEFF Research Database (Denmark)

    Michelsen, Axel Gottlieb; Rathcke, C.N.; Skjelland, M.

    2010-01-01

    atherosclerosis and 20 healthy controls. Carotid expression of YKL-40 was examined by real time RT-PCR in 57 of the patients. Regulation and effect of YKL-40 were examined in THP-1 monocytes. Results: Our main findings were: (1) serum YKL-40 levels were significantly elevated in patients with carotid...... atherosclerosis, with particularly high levels in those with symptomatic disease; (2) patients with recent ischemic symptoms (within 2 months) had higher YKL-40 mRNA levels in carotid plaque than other patients; (3) in vitro, the beta-adrenergic receptor agonist isoproterenol, toll-like receptor (TLR) 2 and TLR4...

  11. Management of radiation-induced accelerated carotid atherosclerosis

    International Nuclear Information System (INIS)

    Loftus, C.M.; Biller, J.; Hart, M.N.; Cornell, S.H.; Hiratzka, L.F.

    1987-01-01

    Patients with long survival following cervical irradiation are at risk for accelerated carotid atherosclerosis. The neurologic presentation in these patients mimics naturally occurring atheromatous disease, but patients often present at younger ages and with less concurrent coronary or systemic vascular disease. Hypercholesterolemia also contributes to this accelerated arteriosclerosis. Angiographic findings in this disorder include disproportionate involvement of the distal common carotid artery and unusually long carotid lesions. Pathologic findings include destruction of the internal elastic lamina and replacement of the normal intima and media with fibrous tissue. This article describes two surgical patients with radiation-induced accelerated carotid atherosclerosis who typify the presentation and characteristics of this disease

  12. [¹⁸F]-fluorodeoxyglucose PET imaging of atherosclerosis

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Høilund-Carlsen, Poul Flemming

    2015-01-01

    [(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk...... of atherosclerosis-related disease, such as stroke and myocardial infarction. With excellent reproducibility, (18)FDG PET can be a surrogate end point in clinical drug trials, improving trial efficiency. This article summarizes key findings in the literature, discusses limitations of (18)FDG PET imaging...

  13. Lutein and atherosclerosis: Belfast versus Toulouse revisited.

    Science.gov (United States)

    Howard, A N; Thurnham, D I

    2017-01-01

    have been due to the effects of concurrent high concentrations of plasma lutein on the immune system and complement in particular. Other carotenoids may exert similar antioxidant effects but we and others found no differences in antioxidant nutrients between subjects in Toulouse and Belfast or between subjects with asymptomatic markers of atherosclerosis and controls. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

    Energy Technology Data Exchange (ETDEWEB)

    Foss, Catherine A., E-mail: cfoss1@jhmi.edu [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Bedja, Djahida [Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Faculty of Medicine and Health Sciences, Macquarie University, Sydney (Australia); Mease, Ronnie C.; Wang, Haofan [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Kass, David A. [Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Chatterjee, Subroto [Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Pomper, Martin G. [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States)

    2015-05-22

    Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.

  15. Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

    International Nuclear Information System (INIS)

    Foss, Catherine A.; Bedja, Djahida; Mease, Ronnie C.; Wang, Haofan; Kass, David A.; Chatterjee, Subroto; Pomper, Martin G.

    2015-01-01

    Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [ 125 I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [ 125 I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h

  16. Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Dipti Deshpande

    Full Text Available Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/- mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease.

  17. Effects of BM-573 on Endothelial Dependent Relaxation and Increased Blood Pressure at Early Stages of Atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Miguel Romero

    Full Text Available Endothelial dysfunction is considered to be an early event in atherosclerosis and plays a pivotal role in the development, progression and clinical complications of atherosclerosis. Previous studies have shown the beneficial effects of combined inhibition of thromboxane synthase and antagonism of thromboxane receptors by BM-573 on atherosclerosis; however our knowledge about the beneficial effects of BM-573 on endothelial function and increased blood pressure related to early stage of atherosclerosis is limited. In the present study, we investigated the effects of short-term (3 μM, 1 hour and chronic (10 mg/L, 8 weeks treatments with BM-573 on vasodilatory function, nitric oxide (NO bioavailability, oxidative stress and systolic blood pressure in 15 weeks old apolipoprotein E-deficient (ApoE-KO mice. ApoE-KO mice showed a reduced endothelium-derived relaxation. In addition, NO bioavailability was reduced and oxidative stress and blood pressure were increased in ApoE-KO mice versus wild-type mice. BM-573 treatments were able to improve the relaxation profile in ApoE-KO mice. Short-term effects of BM-573 were mainly mediated by an increased phosphorylation of both eNOS and Akt, whereas BM-573 in vivo treatment also reduced oxidative stress and restored NO bioavailability. In addition, chronic administration of BM-573 reduced systolic blood pressure in ApoE-KO mice. In conclusion, pharmacological modulation of TxA2 biosynthesis and biological activities by dual TP antagonism/TxAS inhibition with BM-573, already known to prevent plaque formation, has the potential to correct vasodilatory dysfunction at the early stages of atherosclerosis.

  18. Coronary artery atherosclerosis associated with shift work in chemical plant workers by using coronary CT angiography.

    Science.gov (United States)

    Kang, WonYang; Park, Won-Ju; Jang, Keun-Ho; Kim, Soo-Hyeon; Gwon, Do-Hyeong; Lim, Hyeong-Min; Ahn, Ji-Sung; Moon, Jai-Dong

    2016-08-01

    The aim of this study was to investigate whether shift work is related to elevated risk of coronary artery disease (CAD) by determining the coronary artery calcium (CAC) score and the presence of coronary artery stenosis by using coronary artery CT angiography (CCTA). In this study, 110 male workers participated and underwent a CCTA examination for CAC scoring, which represents coronary artery plaque, and were evaluated for luminal stenosis. All of the participants were working in the same chemical plant, of whom 70 worked day shifts and 40 worked rotating shifts. In a multivariate logistic regression analysis, including age, smoking status, alcohol consumption, regular exercise and waist circumference, shift work was associated with a 2.89-fold increase in the odds of developing coronary plaque compared with day work (OR, 2.89; 95% CI 1.07 to 7.82). The association between shift work and coronary plaque was strong after adjustment for age, low-density lipoprotein cholesterol, hypertension and diabetes mellitus (OR, 2.92; 95% CI 1.02 to 8.33). In addition, the number of years of shift work employment was associated with coronary plaque. However, no association was found between shift work and coronary artery stenosis. Shift work could induce CAD onset via the atherosclerotic process, and shift work employment duration was associated with an increased risk of atherosclerosis in male workers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. 48 CFR 235.070-1 - Indemnification under research and development contracts.

    Science.gov (United States)

    2010-10-01

    ... research and development contracts. 235.070-1 Section 235.070-1 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 235.070-1 Indemnification under research and development contracts. (a...

  20. Computational studies of global nuclear energy development under the assumption of the world's heterogeneous development

    International Nuclear Information System (INIS)

    Egorov, A.F.; Korobejnikov, V.V.; Poplavskaya, E.V.; Fesenko, G.A.

    2013-01-01

    Authors study the mathematical model of Global nuclear energy development until the end of this century. For comparative scenarios analysis of transition to sustainable nuclear energy systems, the models of heterogeneous world with an allowance for specific national development are under investigation [ru

  1. Continuous Drip Flow System to Develop Biofilm of E. faecalis under Anaerobic Conditions

    Directory of Open Access Journals (Sweden)

    Ana Maria Gonzalez

    2014-01-01

    Full Text Available Purpose. To evaluate a structurally mature E. faecalis biofilm developed under anaerobic/dynamic conditions in an in vitro system. Methods. An experimental device was developed using a continuous drip flow system designed to develop biofilm under anaerobic conditions. The inoculum was replaced every 24 hours with a fresh growth medium for up to 10 days to feed the system. Gram staining was done every 24 hours to control the microorganism purity. Biofilms developed under the system were evaluated under the scanning electron microscope (SEM. Results. SEM micrographs demonstrated mushroom-shaped structures, corresponding to a mature E. faecalis biofilm. In the mature biofilm bacterial cells are totally encased in a polymeric extracellular matrix. Conclusions. The proposed in vitro system model provides an additional useful tool to study the biofilm concept in endodontic microbiology, allowing for a better understanding of persistent root canal infections.

  2. Electric Field Induced Strain in Electrostrictive Polymers Under High Hydrostatic Pressure - System Development and Material Characterization

    National Research Council Canada - National Science Library

    Zhang, Q

    2000-01-01

    ... of (i) developing a high performance piezo-bimorph based dilatometer which can be used to characterize the electric field induced strain response in polymer films under high hydrostatic pressure, (ii...

  3. Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes

    NARCIS (Netherlands)

    Aengevaeren, Vincent L; Mosterd, Arend; Braber, Thijs L; Prakken, Niek H J; Doevendans, Pieter A; Grobbee, Diederick E; Thompson, Paul D; Eijsvogels, Thijs M H; Velthuis, Birgitta K

    2017-01-01

    BACKGROUND: Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-esponse relationship of exercise and cardiovascular disease outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We

  4. Insulin resistance and atherosclerosis : the role of visceral fat

    NARCIS (Netherlands)

    Gast, K.B.

    2016-01-01

    The main objective of this thesis was to unravel relationships between obesity, insulin resistance, hyperglycemia, and atherosclerosis. It is well-established that patients with type 2 diabetes have a 2- to 3-fold increased risk of cardiovascular disease. We investigated whether insulin resistance

  5. Oxidation of LDL and extent of peripheral atherosclerosis

    NARCIS (Netherlands)

    Vijver, L.P.L. van de; Kardinaal, A.F.M.; Duyvenvoorde, W. van; Kruijssen, D.A.C.M.; Grobbee, D.E.; Poppel, G. van; Princen, H.M.G.

    1999-01-01

    Evidence has accumulated for oxidative modification of low-density lipoproteins (LDL) to play an important role in the atherogenic process. Therefore, we investigated the relation between susceptibility of LDL to oxidation and risk of peripheral atherosclerosis among 249 men between 45 and 80 years

  6. Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

    Science.gov (United States)

    Uryga, Anna K; Bennett, Martin R

    2016-04-15

    Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  7. Inflammatory markers and extent and progression of early atherosclerosis

    DEFF Research Database (Denmark)

    Willeit, Peter; Thompson, Simon G; Agewall, Stefan

    2016-01-01

    BACKGROUND: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT)...

  8. Genomic Analysis of Circulating Cells: A Window into Atherosclerosis

    Science.gov (United States)

    Kang, Ju-Gyeong; Patino, Willmar D.; Matoba, Satoaki; Hwang, Paul M.

    2006-01-01

    Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments using diseased tissue or surrogate specimens. This review details the rationale and findings of a study using freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched normal subjects. Using this cardiovascular tissue surrogate, the mRNA levels of the Finkel-Biskis-Jinkins osteosarcoma (FOS) gene in circulating monocytes were found to correlate with atherosclerosis severity in patients, and with HMG CoA reductase inhibitor (statin) therapy in normal subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate their reports. They also provide us with insights into pathogenesis that may impact future translational applications. PMID:16781950

  9. Control of Atherosclerosis Regression by PRMT2 in Diabetes

    Science.gov (United States)

    2017-08-01

    Macrophage Dysfunction in Obesity , Diabetes and Atherosclerosis Time Commitment: 3.0 Cal Months Supporting Agency: NHLBI Grants Officer: John Diggs...Project Goals: This sub-project focuses on the kinetics of the macrophage population in atherosclerotic plaques in a mouse model of psychological

  10. Histomorphological features of atherosclerosis in the left anterior ...

    African Journals Online (AJOL)

    The pattern of coronary artery atherosclerosis is valuable in informing mitigation strategies for coronary heart disease. Histomorphological data on this disease among Africans living in Sub Saharan Africa are, however, scarce. The left anterior descending is one of the most commonly afflicted arteries. This study, therefore ...

  11. Atherosclerosis and Nutrition with Special Reference to Populations ...

    African Journals Online (AJOL)

    Severe atherosclerosis and its sequelae-coronary heart disease, cerebral vascular disease, and peripheral vascular disease-share major responsibility for half the mortality rate in affluent Western populations. In Africa, particularly South Africa, a study of the extent and severity of lesions is particularly interesting because of ...

  12. Atherosclerosis and Nutrition with Special Reference to Populations ...

    African Journals Online (AJOL)

    Severe atherosclerosis and its sequelae-coronary heart disease, cerebral ... the different population groups in various stages of tran- sition. ... 'These data show how emotional challenges may produce conspicuous .... and coronary arteries of White men. ... evidence of left ventricular hypertrophy, and glucose in- tolerance ...

  13. Human Low Density Lipoprotein as a Vehicle of Atherosclerosis ...

    African Journals Online (AJOL)

    Low-density lipoproteins have been sufficiently established as an important precursor of atherosclerosis. The actual mechanism is still unclear, and the current technique of using radioisotopes has clinical limitation. However, the current study techniques or methods excellently elucidate the functional aspects of ...

  14. The biology of atherosclerosis: general paradigms and distinct pathogenic mechanisms among HIV-infected patients.

    Science.gov (United States)

    Lo, Janet; Plutzky, Jorge

    2012-06-01

    Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infected patients is needed. Key concepts in atherosclerosis are reviewed, including the evidence that inflammation and abnormal metabolism are major drivers of atherosclerosis, and connected to the current literature regarding atherosclerosis in the context of HIV.

  15. Equol Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice by Inhibiting Endoplasmic Reticulum Stress via Activation of Nrf2 in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Ting Zhang

    Full Text Available The development of atherosclerosis is closely related to excessive endoplasmic reticulum stress (ERs. Equol reportedly protects against cardiovascular disease; however, the underlying mechanism for this protection remains unknown. Herein, the mechanisms contributing to the atheroprotective effect of equol were addressed using apolipoprotein E knockout (apoE-/- mice fed a high-fat diet (HFD with or without equol. Equol intervention reduced atherosclerotic lesions in the aorta in HFD-fed apoE-/- mice. Plasma lipid analysis showed that equol intervention reduced triglycerides, total cholesterol and LDL-cholesterol and increased HDL-cholesterol. Additionally, equol administration decreased lipid accumulation in the liver. Simultaneously, equol treatment inhibited cell apoptosis induced by t-BHP and thapsigargin in human umbilical vein endothelial cells (HUVECs. Furthermore, equol treatment attenuated palmitate, t-BHP or thapsigargin-induced upregulation of ER stress markers, including p-PERK, p-eIF2α, GRP78, ATF6 and CHOP proteins expression. The same tendency was also observed in aortic lysates in apoE-/- mice fed with equol plus HFD compared with HFD alone. Moreover, equol treatment dose dependently activated the Nrf2 signaling pathway under oxidative stress. Additionally, elevation of Nrf2 induction was found in aortic lysates in apoE-/- mice fed with a HFD diet containing equol compared with a HFD diet without equol. Importantly, Nrf2 siRNA interference induced CHOP and attenuated the effect of equol to inhibit t-BHP mediated CHOP induction, furthermore, abrogated cell apoptosis induced by t-BHP, suggesting a role for Nrf2 in the protective effect of equol in HUVECs. Collectively, these findings implicate that the improvement of atherosclerosis by equol through attenuation of ER stress is mediated, at least in part, by activating the Nrf2 signaling pathway.

  16. Early atherosclerosis and vascular inflammation in mice with diet-induced type 2 diabetes

    DEFF Research Database (Denmark)

    Bartels, E D; Bang, C A; Nielsen, L B

    2009-01-01

    and the median lesion area was 8.0 times higher than in fat-fed wild-type mice (P = 0.001). Intracellular adhesion molecule-1 staining of the aortic endothelium was most pronounced in the fat-fed apoB transgenic mice. CONCLUSIONS: Our findings suggest that diet-induced type 2 diabetes causes early......BACKGROUND: Obesity and type 2 diabetes increase the risk of atherosclerosis. It is unknown to what extent this reflects direct effects on the arterial wall or secondary effects of hyperlipidaemia. MATERIALS AND METHODS: The effect of obesity and type 2 diabetes on the development...

  17. Kefiran reduces atherosclerosis in rabbits fed a high cholesterol diet.

    Science.gov (United States)

    Uchida, Masashi; Ishii, Itsuko; Inoue, Chika; Akisato, Yoshie; Watanabe, Kenta; Hosoyama, Saori; Toida, Toshihiko; Ariyoshi, Noritaka; Kitada, Mitsukazu

    2010-09-30

    Kefiran is an exopolysaccharide produced by Lactobacillus kefiranofaciens, and has been proposed to have many health-promoting properties. We investigated the antiatherogenic effect of kefiran on rabbits fed a high-cholesterol diet. Male New Zealand White rabbits were fed a 0.5% cholesterol diet without (control group, n = 7) or with kefiran (kefiran group, n = 8) for eight weeks. The aorta was analyzed by histochemistry and atherosclerotic lesions were quantified. Lipids and sugars in serum were measured. Foam cell formation of RAW264.7 by βVLDL derived from both groups of rabbits was also investigated. Cholesterol, triglyceride and phospholipids levels of serum and lipoprotein fractions were not significantly different between these groups. Atherosclerotic lesions of the aorta in the kefiran group were statistically lower than those of the control group, with marked differences in the abdominal aorta. T-lymphocytes were not detectable in the aorta of the kefiran group. Cholesterol contents in stools were almost identical in both groups. Cholesterol content in the liver of the kefiran group was statistically lower than in the control group. Galactose content of βVLDL derived from the kefiran group was higher, and the lipid peroxidation level was much lower than in the control group. RAW264.7 macrophages treated with βVLDL from the kefiran group showed a more spherical shape and accumulated statistically lower cholesterol than macrophages treated with βVLDL from the control group. Orally derived kefiran is absorbed in the blood. Kefiran prevents the onset and development of atherosclerosis in hypercholesterolemic rabbits by anti-inflammatory and anti-oxidant actions.

  18. Germinated Brown Rice Attenuates Atherosclerosis and Vascular Inflammation in Low-Density Lipoprotein Receptor-Knockout Mice.

    Science.gov (United States)

    Zhao, Ruozhi; Ghazzawi, Nora; Wu, Jiansu; Le, Khuong; Li, Chunyang; Moghadasian, Mohammed H; Siow, Yaw L; Apea-Bah, Franklin B; Beta, Trust; Yin, Zhengfeng; Shen, Garry X

    2018-05-02

    The present study investigates the impact of germinated brown rice (GBR) on atherosclerosis and the underlying mechanism in low-density lipoprotein receptor-knockout (LDLr-KO) mice. The intensity of atherosclerosis in aortas of LDLr-KO mice receiving diet supplemented with 60% GBR (weight/weight) was significantly less than that in mice fed with 60% white rice (WR) or control diet ( p mice fed with WR diet was significantly more than that from mice receiving the control diet ( p mice in comparison to the WR diet ( p mice compared to WR. The anti-atherosclerotic effect of GBR in LDLr-KO mice at least in part results from its anti-inflammatory activity.

  19. Effects of total glucosides from paeony (Paeonia lactiflora Pall) roots on experimental atherosclerosis in rats.

    Science.gov (United States)

    Li, Jing; Chen, Chang Xun; Shen, Yun Hui

    2011-05-17

    Total glucosides of paeony (TGP), compounds extracted from the roots of Paeonia lactiflora Pall, have been used as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) in China. Inflammation plays a critical role in the development of atherosclerotic vascular disease. Risk of cardiovascular diseases is significantly higher in patients with RA than in normal population. It has a great significance to study the effects of TGP on atherosclerosis. To investigate the effects of TGP on atherosclerosis induced by excessive administration of vitamin D and cholesterol in rats and study the mechanisms involved. Atherosclerosis was induced by excessive administration of vitamin D and cholesterol in rats. TGP was intragastrically administered for 15 weeks. The serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) were measured by automatic biochemistry analyzer. Apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) were determined by immunoturbidimetry method, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay (ELISA) method. The morphological changes of aorta were observed with optical microscopy. Compared to controls, TGP significantly lowered the serum level of TC, TG, LDL-C, ApoB, TNF-alpha, IL-6 and CRP, increased the ratios of HDL-C/LDL-C and ApoA1/ApoB, decreased the intima-media thickness (IMT) of abdominal aortal wall and improved the morphological change of the aorta. TGP may attenuate the development of atherosclerotic disease. The beneficial effects are associated with its lowering blood lipids and inhibiting the expression of inflammatory cytokines. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. The role of shear stress and arteriogenesis in maintaining vascular homeostasis and preventing cerebral atherosclerosis

    Directory of Open Access Journals (Sweden)

    David Della-Morte

    2015-01-01

    Full Text Available Shear stress (SS is a biomechanical force that is determined by blood flow, vessel geometry, and fluid viscosity. Although a wide range of known vascular risk factors promote development of atherosclerosis, atherosclerotic changes occur predominately at specific sites within the arterial tree, suggesting a critical role for local factors within the vasculature. Atherosclerotic lesions develop predominantly at branches, bends, and bifurcations in the arterial tree because these sites are exposed to low or disturbed blood flow and low SS. Low SS predisposes arteries to atherosclerosis by causing endothelial dysfunction. A natural system of preexisting cerebral collateral arteries protects against ischemia by bypassing sites of arterial occlusion through a mechanism of arteriogenesis. The main trigger for arteriogenesis is impaired vascular homeostasis (VH in response to local changes in SS induced by ischemia. VH is a critical process for maintaining the physiological function of cerebral circulation. It is regulated through a complex biological system of blood flow hemodynamic and physiological responses to flow changes. Restoration of VH by increasing arteriogenesis and SS may provide a novel therapeutic target for stroke, especially in the elderly, who are more prone to VH impairment. In this review article, we discuss the mechanisms and structures necessary to maintain VH in brain circulation, the role of SS, and risk factors leading to atherosclerosis, including the effects of aging. We also discuss arteriogenesis as an adaptive and protective process in response to ischemic injury, the imaging techniques currently available to evaluate arterogenesis such as magnetic resonance imaging/positron emission tomography (MRI/PET, and the potential therapeutic approaches against ischemic injury that target arteriogenesis.

  1. Reporting standards for angioplasty and stent-assisted angioplasty for intracranial atherosclerosis.

    Science.gov (United States)

    Schumacher, H Christian; Meyers, Philip M; Higashida, Randall T; Derdeyn, Colin P; Lavine, Sean D; Nesbit, Gary M; Sacks, David; Rasmussen, Peter; Wechsler, Lawrence R

    2010-12-01

    Intracranial cerebral atherosclerosis causes ischemic stroke in a significant number of patients. Technological advances over the past 10 years have enabled endovascular treatment of intracranial atherosclerotic stenosis. The number of patients treated with angioplasty or stent-assisted angioplasty for this condition is increasing. Given the lack of universally accepted definitions, the goal of this document is to provide consensus recommendations for reporting standards, terminology, and written definitions when reporting clinical and radiological evaluation, technique, and outcome of endovascular treatment using angioplasty or stent-assisted angioplasty for stenotic and occlusive intracranial atherosclerosis. This article was written under the auspices of Joint Writing Group of the Technology Assessment Committee, Society of Neurolnterventional Surgery, Society of Interventional Radiology; Joint Section on Cerebro-vascular Neurosurgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and the Section of Stroke and Interventional Neurology of the American Academy of Neurology. A computerized search of the National Library of Medicine database of literature (PubMed) from January 1997 to December 2007 was conducted with the goal to identify published endovascular cerebrovascular interventional data in stenotic intracranial atherosclerosis that could be used as benchmarks for quality assessment. We sought to identify those risk adjustment variables that affect the likelihood of success and complications. This document offers the rationale for different clinical and technical considerations that may be important during the design of clinical trials for endovascular treatment of intracranial stenotic and occlusive atherosclerosis. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are primarily intended for research purposes; however, they should

  2. Postnatal development of the hippocampal dentate gyrus under normal and experimental conditions

    International Nuclear Information System (INIS)

    Altman, J.; Bayer, S.

    Studies on postnatal maturation of the dentate gyrus are reviewed. Some topics discussed are: normal development of the dentate gyrus, cytogenesis, morphogenesis, synaptogenesis, gleogenesis, myelogenesis, development of the gyrus under experimental conditions, and effects of x radiation on cytogenesis and morphogenesis

  3. Factors associated with the risk of caries development after comprehensive dental rehabilitation under general anesthesia

    Directory of Open Access Journals (Sweden)

    Yai-Tin Lin

    2016-06-01

    Conclusion: This study has shown that SM count and CRA score were associated with new caries development in ECC children who needed to be treated under general anesthesia. The modified Cariogram used in this study is another significant tool for predicting new carries development in this particular population.

  4. 38 CFR 21.382 - Training and staff development for personnel providing assistance under Chapter 31.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Training and staff....382 Training and staff development for personnel providing assistance under Chapter 31. (a) General. VA shall provide a program of ongoing professional training and development for staff of the VR&E...

  5. Imaging atherosclerosis with hybrid [18F]fluorodeoxyglucose positron emission tomography/computed tomography imaging: what Leonardo da Vinci could not see.

    Science.gov (United States)

    Cocker, Myra S; Mc Ardle, Brian; Spence, J David; Lum, Cheemun; Hammond, Robert R; Ongaro, Deidre C; McDonald, Matthew A; Dekemp, Robert A; Tardif, Jean-Claude; Beanlands, Rob S B

    2012-12-01

    Prodigious efforts and landmark discoveries have led toward significant advances in our understanding of atherosclerosis. Despite significant efforts, atherosclerosis continues globally to be a leading cause of mortality and reduced quality of life. With surges in the prevalence of obesity and diabetes, atherosclerosis is expected to have an even more pronounced impact upon the global burden of disease. It is imperative to develop strategies for the early detection of disease. Positron emission tomography (PET) imaging utilizing [(18)F]fluorodeoxyglucose (FDG) may provide a non-invasive means of characterizing inflammatory activity within atherosclerotic plaque, thus serving as a surrogate biomarker for detecting vulnerable plaque. The aim of this review is to explore the rationale for performing FDG imaging, provide an overview into the mechanism of action, and summarize findings from the early application of FDG PET imaging in the clinical setting to evaluate vascular disease. Alternative imaging biomarkers and approaches are briefly discussed.

  6. Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice.

    Science.gov (United States)

    Li, Melissa W; Mian, Muhammad Oneeb Rehman; Barhoumi, Tlili; Rehman, Asia; Mann, Koren; Paradis, Pierre; Schiffrin, Ernesto L

    2013-10-01

    Endothelin (ET)-1 plays a role in vascular reactive oxygen species production and inflammation. ET-1 has been implicated in human atherosclerosis and abdominal aortic aneurysm (AAA) development. ET-1 overexpression exacerbates high-fat diet-induced atherosclerosis in apolipoprotein E(-/-) (Apoe(-/-)) mice. ET-1-induced reactive oxygen species and inflammation may contribute to atherosclerosis progression and AAA development. Eight-week-old male wild-type mice, transgenic mice overexpressing ET-1 selectively in endothelium (eET-1), Apoe(-/-) mice, and eET-1/Apoe(-/-) mice were fed high-fat diet for 8 weeks. eET-1/Apoe(-/-) had a 45% reduction in plasma high-density lipoprotein (P<0.05) and presented ≥ 2-fold more aortic atherosclerotic lesions compared with Apoe(-/-) (P<0.01). AAAs were detected only in eET-1/Apoe(-/-) (8/21; P<0.05). Reactive oxygen species production was increased ≥ 2-fold in perivascular fat, media, or atherosclerotic lesions in the ascending aorta and AAAs of eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). Monocyte/macrophage infiltration was enhanced ≥ 2.5-fold in perivascular fat of ascending aorta and AAAs in eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). CD4(+) T cells were detected almost exclusively in perivascular fat (3/6) and atherosclerotic lesions (5/6) in ascending aorta of eET-1/Apoe(-/-) (P<0.05). The percentage of spleen proinflammatory Ly-6C(hi) monocytes was enhanced 26% by ET-1 overexpression in Apoe(-/-) (P<0.05), and matrix metalloproteinase-2 was increased 2-fold in plaques of eET-1/Apoe(-/-) (P<0.05) compared with Apoe(-/-). ET-1 plays a role in progression of atherosclerosis and AAA formation by decreasing high-density lipoprotein, and increasing oxidative stress, inflammatory cell infiltration, and matrix metalloproteinase-2 in perivascular fat, vascular wall, and atherosclerotic lesions.

  7. Diagnosing Management of Agricultural Research and Technology Development under the Agricultural Innovation Framework

    Directory of Open Access Journals (Sweden)

    2014-06-01

    Full Text Available This study aimed at identifying and analyzing issues and challenges on the agricultural research and technology development under the national innovation framework. The survey consisted of two groups: agricultural researchers of Agriculture-Research and Education Organization and all faculty members of public agricultural faculties of Ministry of Scientific, Research and Technology. Using Cochran sampling formula and multi-stage sampling method, 188 researchers and 205 faculty members were selected in order to fill in the survey questionnaire. Using the SPSS, collected data analyzed based on explanatory factor analysis. Totally, factor analysis of three sets of issues and challenges on the agricultural research and technology development under the national innovation framework led to extract 13 factors, including agricultural structure and policy, infrastructure and resources of agricultural development, supportive services for agricultural development (level of agricultural development, investment and capacity building in research and technology, management of research and technology development, research and technology productivity, research culture, networks for research and technology development (level of national innovation system, agricultural research policy, impacts and effectiveness of agricultural research and technology development, integrated management of research and technology, institutional development for agricultural research and technology and systematic synergy of agricultural research and higher education (level of agricultural innovation system. Totally, these three sets of factors explained 64%, 75% and 73% of the total variances. Finally, using conceptual clustering for the extracted factors, a conceptual model of issues and challenges of agricultural research and technology development under the national innovation framework was presented.

  8. Uric Acid, Metabolic Syndrome and Atherosclerosis: The Chicken or the Egg, Which Comes First?

    Science.gov (United States)

    De Pergola, Giovanni; Cortese, Francesca; Termine, Gaetano; Meliota, Giovanni; Carbonara, Rossella; Masiello, Michele; Cortese, Anna M; Silvestris, Francesco; Caccavo, Domenico; Ciccone, Marco Matteo

    2018-01-01

    A great debate in literature exists nowadays on the role of uric acid as a marker of cardiovascular and metabolic organ damage or a risk factor for cardiovascular and metabolic disease. The study aimed to determine the relationship among serum uric acid and metabolic syndrome and atherosclerosis, by means of carotid intima media-thickness, in a cohort of 811 otherwise healthy overweight/obese subjects, without overt atherosclerosis not using any kind of drug. Uric acid levels were positively related to male gender, waist circumference, BMI, systolic and diastolic pressure levels, fasting insulin, fasting glucose, HOMA-IR, triglycerides, total cholesterol, LDL cholesterol, the presence of metabolic syndrome and the number of the components of metabolic syndrome and negatively related to HDL cholesterol levels. No correlation was found between uric acid and carotid intima media thickness. At the multiple regression analysis, only waist circumference and triglycerides (positively) and HDL-cholesterol (negatively) maintained an independent association with uric acid as dependent variable, while age, female gender and uric acid showed a significant independent association with metabolic syndrome as dependent variable. Moreover, the analysis of the odd ratios showed that the risk of developing metabolic syndrome was consistent with uric acid levels ranging from 3 mg/dl to 8 mg/dl. The presence of metabolic syndrome does not seem to provide hyperuricemia. By contrast, higher serum uric acid level may predict the risk of metabolic syndrome. Moreover, our results suggest that uric acid cannot be considered a risk factor for early atherosclerosis, at least when assessed using carotid ultrasound. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Deficiency of ABCA1 and ABCG1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

    Science.gov (United States)

    Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

    2013-01-01

    Rationale Plasma HDL levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is due to the ability of HDL to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results We developed MAC-ABCDKO mice with efficient deletion of the ATP Binding Cassette Transporters A1 and G1 (ABCA1 and ABCG1) in macrophages but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr-/- recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared to controls. On the Western type diet (WTD), MAC-ABCDKO BM transplanted Ldlr-/- mice had disproportionate atherosclerosis, considering they also had lower VLDL/LDL cholesterol levels than controls. ABCA1/G1 deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, WTD-fed MAC-ABCDKO BM transplanted Ldlr-/- mice displayed monocytosis and neutrophilia in the absence of HSPC proliferation. Mechanistic studies revealed increased expression of M-CSF and G-CSF in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusion These studies 1) show that macrophage deficiency of ABCA1/G1 is pro-atherogenic likely by promoting plaque inflammation and 2) uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways. PMID:23572498

  10. Polyunsaturated fats, carbohydrates and carotid disease: The Atherosclerosis Risk in Communities (ARIC) Carotid MRI study.

    Science.gov (United States)

    Dearborn, Jennifer L; Qiao, Ye; Guallar, Eliseo; Steffen, Lyn M; Gottesman, Rebecca F; Zhang, Yiyi; Wasserman, Bruce A

    2016-08-01

    Carbohydrates and fat intake have both been linked to development of atherosclerosis. We examined associations between glycemic index (GI) and fat intake with carotid atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) cohort enrolled participants during the period 1987-1989 and the Carotid MRI sub-study occurred between 2004 and 2006 (1672 participants attending both visits). Measures of carbohydrate quality (usual GI), fat intake (total, polyunsaturated and saturated) and overall dietary quality index (DASH Diet Score) were derived from a 66-item food frequency questionnaire administered at baseline. Trained readers measured lipid core presence and maximum wall thickness. Using multivariate logistic regression, we determined the odds of lipid core presence by quintile (Q) of energy-adjusted dietary components. Restricted cubic spline models were used to examine non-linear associations between dietary components and maximum wall thickness. Mean daily polyunsaturated fat intake was 5 g (SD 1.4). GI and polyunsaturated fat intake had a nonlinear relationship with maximum wall thickness. Low (1-4 g) and high (6-12 g) polyunsaturated fat intake were associated with a statistically significant decreased odds of lipid core presence compared to intake in a majority of participants (OR Q5 vs. Q2-4: 0.64, 95% CI 0.42 to 0.98; OR Q1 vs. Q2-4: 0.64, 95% CI 0.42, 0.96), however, the association with lipid core was attenuated by adjustment for maximum wall thickness, hypertension, hyperlipidemia, and diabetes. GI and polyunsaturated fat intake were not associated with high-risk plaque features, such as lipid core presence, independent of traditional vascular risk factors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Subclinical atherosclerosis in young patients with rheumatoid arthritis and low disease activity

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    F. Ragni Alunni

    2011-09-01

    Full Text Available Background: There is an increasing body of evidence suggesting that subjects with rheumatoid arthritis (RA are characterized by acceleration of atherosclerotic process of arterial wall. However, all investigations performed so far to evaluate subclinical atherosclerosis in RA included subjects without selection for age and degree of disease activity that may represent confounding factors in such an evaluation. Objectives: To verify signs of accelerated subclinical atherosclerosis in young subject suffering from RA but with low disease activity. Methods: Thirty-two patients with RA and 28 age- and sex-matched control subjects with non-inflammatory rheumatic diseases were enrolled. Inclusion criteria were age less than 60 and low disease activity with score £3.2 according to DAS28, while subjects with traditional risk factors for and/or overt cardiovascular disease were ruled out from the study. Both patients and controls underwent evaluation of carotid and femoral artery intima-media thickness by ultrasounds. Results: Patients had higher intima-media thickness than controls of all the sites evaluated at carodit artery level, whereas there were no differences at the comparison of the superficial and common femoral artery wall. At the univariate analysis, a positive correlation between LDL cholesterol levels and intima-media thickness at the carotid bifurcation was found. Conclusions: Young patients with RA and low disease activity have acceleration of atherosclerosis development as shown by increased intima-media thickness of carotid artery with respect to subjects without inflammatory rheumatic disease. It is conceivable that the organic damage of arterial wall could be the result of persistent endothelial dysfunction induced by chronic inflammation and immune dysregulation which characterize RA.

  12. Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis

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    Wang Linjie

    2011-10-01

    Full Text Available Abstract Background Growing evidence suggests that epicardial adipose tissue (EAT may play a key role in the pathogenesis and development of coronary artery disease (CAD by producing several inflammatory adipokines. Chemerin, a novel adipokine, has been reported to be involved in regulating immune responses and glucolipid metabolism. Given these properties, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis. In this study, we sought to determine the relationship of chemerin expression in EAT and the severity of coronary atherosclerosis in Han Chinese patients. Methods Serums and adipose tissue biopsies (epicardial and thoracic subcutaneous were obtained from CAD (n = 37 and NCAD (n = 16 patients undergoing elective cardiac surgery. Gensini score was used to assess the severity of CAD. Serum levels of chemerin, adiponectin and insulin were measured by ELISA. Chemerin protein expression in adipose tissue was detected by immunohistochemistry. The mRNA levels of chemerin, chemR23, adiponectin and TNF-alpha in adipose tissue were detected by RT-PCR. Results We found that EAT of CAD group showed significantly higher levels of chemerin and TNF-alpha mRNA, and significantly lower level of adiponectin mRNA than that of NCAD patients. In CAD group, significantly higher levels of chemerin mRNA and protein were observed in EAT than in paired subcutaneous adipose tissue (SAT, whereas such significant difference was not found in NCAD group. Chemerin mRNA expression in EAT was positively correlated with Gensini score (r = 0.365, P P P P P P P > 0.05. Conclusions The expressions of chemerin mRNA and protein are significantly higher in EAT from patients with CAD in Han Chinese patients. Furthermore, the severity of coronary atherosclerosis is positive correlated with the level of chemerin mRNA in EAT rather than its circulating level.

  13. Intake of antioxidants and B vitamins is inversely associated with ischemic stroke and cerebral atherosclerosis

    Science.gov (United States)

    Choe, Hansaem; Hwang, Ji-Yun; Yun, Jin A; Kim, Ji-Myung; Song, Tae-Jin; Chang, Namsoo; Kim, Yong-Jae

    2016-01-01

    BACKGROUND/OBJECTIVES This study was conducted to examine relationships between dietary habits and intakes of antioxidants and B vitamins and the risk of ischemic stroke, and to compare dietary factors according to the presence of cerebral artery atherosclerosis and stroke subtypes. SUBJECTS/METHODS A total of 147 patients and 144 control subjects were recruited consecutively in the metropolitan area of Seoul, Korea. Sixty participants each in the case and control groups were included in analyses after 1:1 frequency matching. In addition, 117 acute ischemic stroke patients were classified into subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) guidelines. Dietary intake was measured using a semi-quantitative food frequency questionnaire composed of 111 food items and plasma lipid and homocysteine levels were analyzed. RESULTS When compared with control subjects, stroke patients had unfavorable dietary behaviors and lower intakes of fruits (73.1 ± 83.2 g vs. 230.9 ± 202.1 g, P < 0.001), vegetables (221.1 ± 209.0 g vs. 561.7 ± 306.6 g, P < 0.001), and antioxidants, including vitamins C, E, B6, β-carotene, and folate. The intakes of fruits, vegetables, vitamin C, and folate were inversely associated with the risk of ischemic stroke after adjusting for confounding factors. Intakes of vegetables, vitamins C, B6, B12, and folate per 1,000 kcal were lower in ischemic stroke with cerebral atherosclerosis than in those without. Overall vitamin B12 intake per 1,000 kcal differed according to the TOAST classification (P = 0.004), but no differences among groups existed based on the post-hoc test. CONCLUSIONS When compared with control subjects, ischemic stroke patients, particularly those with cerebral atherosclerosis, had unfavorable dietary intake, which may have contributed to the development of ischemic stroke. These results indicate that proper dietary recommendations are important for the prevention of ischemic stroke. PMID:27698959

  14. Selected atherosclerosis risk factors in youth aged 13–15 years 

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    Agnieszka Michalska

    2012-09-01

    Full Text Available Introduction:The high frequency of cases of circulatory system conditions in Europe and other countries around the world requires scientific research to define risk factors of early atherosclerotic changes. The aim of the present study was to define which students are at danger of developing atherosclerosis by means of measuring cholesterol and triglyceride levels in blood as well as defining the correlation between atherosclerosis risk factors and arterial blood pressure, physical fitness and efficiency of the subjects.Material/Methods:The research covered 167 students of Public Junior High School ¹1 in Biala Podlaska aged 13–15 years. Accutrend GCT was employed to define the levels of total cholesterol and triglycerides in the screen test. Those students who were found to have increased values of biochemical parameters of capillary blood were subjected to additional blood tests aiming to define complete lipid profile of venous blood. The blood pressure in subjects was tested three times. The Moderate-to-Vigorous Physical Activity (MVPA test, suggested by American authors, was employed to define physical activity in subjects. EUROFIT was employed to define physical efficiency.Results:Among the 167 subjects there were found 42 students (25.1�20whose lipid level in capillary blood proved to be increased. Full lipid profile tests proved that 16 students (9.6�20had increased blood lipid levels; those subjects constituted the risk group. Subjects in the risk group were characterized by lower levels of physical activity and physical efficiency compared to subjects with normal blood lipid level. Moreover, the frequency of hypertension was greater in risk group subjects compared to subjects with normal blood lipid levels.Inferences:Students diagnosed with atherosclerosis risk factors require observation and early prophylactics by adopting habits of healthy physical activity.

  15. The degree of coronary atherosclerosis as a marker of insulin resistance in non-diabetics

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    Parapid Biljana

    2010-01-01

    Full Text Available Introduction. The metabolic syndrome and its influence on coronary artery disease development and progression remains in focus of international research debates, while insulin resistance, which represents its core, is the key component of hypertension, dyslipidaemias, glucose intolerance and obesity. Objective. The aim of this study was to establish relationship between basal glucose and insulin levels, insulin sensitivity and lipid panel and the degree of coronary atherosclerosis in nondiabetic patients. Methods. The coronary angiograms were evaluated for the presence of significant stenosis, insulin sensitivity was assessed using the intravenous glucose tolerance test with a minimal model according to Bergman, while baseline glucose (G0, insulin (I0 and lipid panel measurements (TC, HDL, LDL, TG were taken after a 12-hour fasting. Results. The protocol encompassed 40 patients (19 men and 21 women treated at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia, Belgrade. All were non-diabetics who were divided into 3 groups based on their angios: Group A (6 patients, 15%, with no significant stenosis, Group B (18 patients, 45%, with a single-vessel disease and Group C (16 patients, 40%, with multi-vessel disease. Presence of lower insulin sensitivity, higher I0 and TC in the group of patients with a more severe degree of coronary atherosclerosis (insulin sensitivity: F=4.279, p=0.023, A vs. C p=0.012, B vs. C p=0.038; I0: F=3.461 p=0.042, A vs. B p=0.045, A vs. C p=0.013; TC: F=2.572, p=0.09, while no significant difference was found for G0, LDL, HDL and TG. Conclusion. Baseline insulinaemia, more precisely, fasting hyperinsulinaemia could be a good predictor of significant coronary atherosclerosis in non-diabetic patients, which enables a more elegant cardiometabolic risk assessment in the setting of everyday clinical practice.

  16. Typological Features of Economic Development in Russian Regions under the Conditions of Development of Continuous Education

    Directory of Open Access Journals (Sweden)

    Sergei Viktorovich Kroshilin

    2015-12-01

    Full Text Available In the modern conditions the socio-economic paradigm is changing, on the one hand, due to the transition to knowledge economy and, on the other hand, due to the need to develop innovation that determine competitiveness and the development level of national economies in the world. It is obvious that the progressive upgrade and the improvement of production processes (change in technological modes can not be implemented without the increase in the level of human capital in the society and the enhancement of potential and qualification of the workforce. These changes largely depend on the education system. In almost all world countries there is an active process of modernization and change in the system of training. New forms and approaches appear, for example lifelong education (concept “Lifelong education”, informal forms of learning, self-education, etc. Without the development of these approaches it is not possible to become a competitive state in changing social, political and economic environment. This is particularly true for countries, which experience changes in the technological mode and have the necessity to transfer to new technologies. Russia is among such countries nowadays. In our opinion, the modern reforms do not give the opportunity to fulfill the main task of education – to ensure and create conditions for self-determination and self-moralization of an individual in the society, achieve the desired level of knowledge for development of innovation in the regions. In the framework of the conducted research we get the classification of all Russian regions by indicators, such as “innovation” and “investment attractiveness”, with the levels of education being taken into account. This approach, on the one hand, shows the heterogeneity of socio-economic development of the country’s regions and, on the other hands, ‒ allows us to reveal the fact that the same federal district can include both regions-locomotives and

  17. Effect of 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin lesions on systemic inflammation and atherosclerosis in hypercholesterolaemic apolipoprotein E deficient mice

    DEFF Research Database (Denmark)

    Madsen, Marie; Hansen, Peter Riis; Nielsen, Lars Bo

    2016-01-01

    BACKGROUND: Risk of cardiovascular disease is increased in patients with psoriasis, but molecular mechanisms linking the two conditions have not been clearly established. Lack of appropriate animal models has hampered generation of new knowledge in this area of research and we therefore sought...... to develop an animal model with combined atherosclerosis and psoriasis-like skin inflammation. METHODS: Topical 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied to the ears twice per week for 8 weeks in atherosclerosis-prone apolipoprotein E deficient (ApoE(-/-)) mice. RESULTS: TPA led to localized...

  18. Lack of relationship between plasma insulin and glucogen levels and angiographically-documented coronary atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Mookherjee, S; Potts, J L; Hill, N E; Warner, R; Raheja, K L; Patel, D G; Vardan, S; Smulyan, H [Upstate Medical Center, Syracuse, NY (USA)

    1983-10-01

    In 120 consecutive patients undergoing diagnostic coronary arteriography, fasting blood glucose, plasma insulin, glucagon, serum cholesterol and triglyceride concentrations were measured. The insulin-glucose ratio and insulin-glucagon ratio were calculated. Forty-five patients had normal coronary arteries, 19 had single vessel coronary artery disease and 56 patients had multiple vessel disease. Fasting blood glucose was >120 mg/100 ml in 37 patients (group A) and included 9 of the 10 known diabetics, 3 of whom were being treated with insulin. Seventy-seven patients included in group B had fasting blood glucose concentration <120 mg/100 ml. Patients with multiple vessel coronary disease in either group had higher blood glucose and cholesterol concentrations than those with normal coronary arteries or glucagon levels nor increased insulin-glucose or insulin-glucagon ratios. With comparable extent of coronary artery disease patients in group A had higher plasma insulin levels and insulin-glucagon ratios than those in group B, but no correlation exists between the presence of extent of coronary atherosclerosis and these variables in either group. Thus, neither fasting plasma insulin level nor insulin-glucagon ratio predicts the status of underlying coronary atherosclerosis in either diabetes or nondiabetes.

  19. Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects.

    Science.gov (United States)

    Ghosh, Siddhartha S; He, Hongliang; Wang, Jing; Gehr, Todd W; Ghosh, Shobha

    2018-01-02

    Curcumin has anti-inflammatory, anti-oxidant and anti-proliferative properties established largely by in vitro studies. Accordingly, oral administration of curcumin beneficially modulates many diseases including diabetes, fatty-liver disease, atherosclerosis, arthritis, cancer and neurological disorders such as depression, Alzheimer's or Parkinson's disease. However, limited bioavailability and inability to detect curcumin in circulation or target tissues has hindered the validation of a causal role. We established curcumin-mediated decrease in the release of gut bacteria-derived lipopolysaccharide (LPS) into circulation by maintaining the integrity of the intestinal barrier function as the mechanism underlying the attenuation of metabolic diseases (diabetes, atherosclerosis, kidney disease) by curcumin supplementation precluding the need for curcumin absorption. In view of the causative role of circulating LPS and resulting chronic inflammation in the development of diseases listed above, this review summarizes the mechanism by which curcumin affects the several layers of the intestinal barrier and, despite negligible absorption, can beneficially modulate these diseases.

  20. DEVELOPMENT OF THE CONCEPT OF CORPORATE SOCIAL RESPONSIBILITY IN TRADE UNDER CONDITIONS OF MARKET GLOBALISATION

    OpenAIRE

    Svetlana Sokolov Mladenovic, Djordje Cuzovic,

    2015-01-01

    Under contemporary business conditions, market globalisation has become inevitable. Such relationships on the market make trade companies use different means to acquire and maintain long-term competitive advantage. One of them is the concept of corporate social responsibility, which is, under conditions of globalisation, seen as a redesign of the classic marketing concept. The aim of this paper is to highlight the development of corporate social responsibility in trade, in the context of mark...

  1. Endothelial Lipase Concentrations Are Increased in Metabolic Syndrome and Associated with Coronary Atherosclerosis.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: Endothelial lipase (EL, a new member of the lipase family, has been shown to modulate high-density lipoprotein (HDL-C metabolism and atherosclerosis in mouse models. We hypothesized that EL concentrations would be associated with decreased HDL-C and increased atherosclerosis in humans. METHODS AND FINDINGS: Healthy individuals with a family history of premature coronary heart disease (n = 858 were recruited as part of the Study of the Inherited Risk of Atherosclerosis. Blood was drawn in the fasting state before and, in a subgroup (n = 510, after administration of a single dose of intravenous heparin. Plasma lipids were measured enzymatically, lipoprotein subclasses were assessed by nuclear magnetic resonance, and coronary artery calcification (CAC was quantified by electron beam computed tomography. Plasma EL mass was measured using a newly developed enzyme-linked immunosorbent assay. Median EL mass in pre-heparin plasma was 442 (interquartile range = 324-617 ng/ml. Median post-heparin mass was approximately 3-fold higher, 1,313 (888-1,927 ng/ml. The correlation between pre-heparin EL mass and post-heparin EL mass was 0.46 (p < 0.001. EL mass concentrations in both pre- and post-heparin plasma significantly correlated with all NCEP ATPIII-defined metabolic syndrome factors: waist circumference (r = 0.28 and 0.22, respectively, p < 0.001 for each, blood pressure (r = 0.18 and 0.24, p < 0.001 for each, triglycerides (r = 0.22, p < 0.001; and 0.13, p = 0.004, HDL cholesterol (r = -0.11, p = 0.002; and -0.18, p < 0.001, and fasting glucose (r = 0.11 and 0.16, p = 0.001 for both. EL mass in both routine (odds ratio [OR] = 1.67, p = 0.01 and post-heparin (OR = 2.42, p = 0.003 plasma was associated with CAC as determined by ordinal regression after adjustment for age, gender, waist circumference, vasoactive medications, hormone replacement therapy (women, and established cardiovascular risk factors. CONCLUSIONS: We report, to our knowledge

  2. ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial.

    Science.gov (United States)

    Meuwese, Marijn C; de Groot, Eric; Duivenvoorden, Raphaël; Trip, Mieke D; Ose, Leiv; Maritz, Frans J; Basart, Dick C G; Kastelein, John J P; Habib, Rafik; Davidson, Michael H; Zwinderman, Aeilko H; Schwocho, Lee R; Stein, Evan A

    2009-03-18

    Inhibition of acyl coenzyme A:cholesterol acyltransferase (ACAT), an intracellular enzyme involved in cholesterol accumulation, with pactimibe was developed to assist in the prevention of cardiovascular disease. To evaluate the efficacy and safety of pactimibe in inhibition of atherosclerosis. A prospective, randomized, stratified, double-blind, placebo-controlled study (Carotid Atherosclerosis Progression Trial Investigating Vascular ACAT Inhibition Treatment Effects [CAPTIVATE]) of 892 patients heterozygous for familial hypercholesterolemia conducted at 40 lipid clinics in the United States, Canada, Europe, South Africa, and Israel between February 1, 2004, and December 31, 2005. Study was terminated on October 26, 2005. Participants received either 100 mg/d of pactimibe (n = 443) or matching placebo (n = 438), in addition to standard lipid-lowering therapy. Carotid atherosclerosis, assessed by ultrasound carotid intima-media thickness (CIMT), at baseline, 12, 18, and 24 months. Maximum CIMT was the primary end point and mean CIMT the secondary end point. Because pactimibe failed to show efficacy in the intravascular coronary ultrasound ACTIVATE study, the CAPTIVATE study was terminated prematurely after a follow-up of 15 months. After 6 months of treatment with pactimibe, low-density lipoprotein cholesterol increased by 7.3% (SD, 23%) compared with 1.4% (SD, 28%) in the placebo group (P = .001). The carotid ultrasonographic scans of the 716 patients with at least 2 scans and obtained at least 40 weeks apart were analyzed. Maximum CIMT measurements did not show a pactimibe treatment effect (difference, 0.004 mm; 95% confidence interval [CI], -0.023 to 0.015 mm; P = .64); however, the less variable mean CIMT measurement revealed an increase of 0.014 mm (95% CI, -0.027 to 0.000 mm; P = .04) in patients administered pactimibe vs placebo. Major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) occurred more often in patients administered

  3. Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Shanshan [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800 (China); Wang, Jiaxing [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Zhang, Xu; Shi, Ying; Li, Bochuan; Bao, Qiankun [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Pang, Wei [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Ai, Ding [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Zhu, Yi [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); He, Jinlong, E-mail: hejinlong@tmu.edu.cn [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China)

    2016-08-19

    Activated vascular endothelium inflammation under persistent hyperlipidemia is the initial step of atherogenesis. ATP-binding cassette G1 (ABCG1) is a crucial factor maintaining sterol and lipid homeostasis by transporting cholesterol efflux to high-density lipoprotein. In this study, we investigated the protective effects of ABCG1 in endothelial inflammation activation during early-stage atherogenesis in mice and the underlying mechanisms. Endothelial cell (EC)-specific ABCG1 transgenic (EC-ABCG1-Tg) mice were generated and cross-bred with low-density lipoprotein receptor–deficient (Ldlr{sup −/−}) mice. After a 4-week Western-type diet, the mice were sacrificed for assessing atherosclerosis. Human umbilical vein ECs were treated with different flows, and ABCG1 was adenovirally overexpressed to investigate the mechanism in vitro. Compared with Ldlr{sup −/−} mouse aortas, EC-ABCG1-Tg/Ldlr{sup −/−} aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr{sup −/−} mouse aortic arch but not thoracic aorta was significantly reduced, which suggests a protective role of ABCG1 under atheroprone flow. In vitro, overexpression of ABCG1 attenuated EC activation caused by oscillatory shear stress. Overexpression of ABCG1 blunted cholesterol-activated ECs in vitro. In exploring the mechanisms of ABCG1 attenuating endothelial inflammation, we found that ABCG1 inhibited oscillatory flow-activated nuclear factor kappa B and NLRP3 inflammasome in ECs. ABCG1 may play a protective role in early-stage atherosclerosis by reducing endothelial activation induced by oscillatory shear stress via suppressing the inflammatory response. - Highlights: • EC-ABCG1-Tg mice in a Ldlr{sup −/−} background showed decreased atherosclerosis. • Overexpression of ABCG1 in ECs decreased OSS-induced EC activation. • NLRP3 and NF-κB might be an underlying mechanism of ABCG1 protective role.

  4. BSN723T Prevents Atherosclerosis and Weight Gain in ApoE Knockout Mice Fed a Western Diet.

    Science.gov (United States)

    Williams, Jarrod; Ensor, Charles; Gardner, Scott; Smith, Rebecca; Lodder, Robert

    This study tests the hypothesis that BSN723T can prevent the development of hyperlipidemia and atherosclerosis in ApoE -/- knockout mice fed a Western (high fat, high cholesterol, and high sucrose) diet. BSN723T is a combination drug therapy consisting of D-tagatose and dihydromyricetin (BSN723). D-tagatose has an antihyperglycemic effect in animal and human studies and shows promise as a treatment for type 2 diabetes and obesity. Many claims regarding BSN723's pharmacological activities have been made including anti-cancer, anti-diabetic, anti-hypertensive, anti-inflammatory, and anti-atherosclerotic effects. To our knowledge this is the first study that combines D-tagatose and BSN723 for the treatment of hyperlipidemia and the prevention of atherosclerosis. ApoE-deficient mice were randomized into five groups with equivalent mean body weights. The mice were given the following diets for 8 weeks: Group 1 - Standard diet; Group 2 - Western diet; Group 3 - Western diet formulated with D-tagatose; Group 4 - Western diet formulated with BSN723; Group 5 - Western diet formulated with BSN723T. Mice were measured for weight gain, tissue and organ weights, total serum cholesterol and triglycerides and formation of atherosclerosis. The addition of D-tagatose, either alone or in combination with BSN723, prevented the increase in adipose tissue and weight gain brought on by the Western diet. Both D-tagatose and BSN723 alone reduced total cholesterol and the formation of atherosclerosis in the aorta compared to mice on the Western diet. Addition of BSN723 to D-tagatose (BSN723T) did not increase efficacy in prevention of increases in cholesterol or atherosclerosis compared to D-tagatose alone. Addition of either D-tagatose or BSN723 alone to a Western diet prevented weight gain, increases in total serum cholesterol and triglycerides, and the formation of atherosclerosis. However, there was no additive or synergistic effect on the measured parameters with the combination BSN

  5. LOX-1 and Its Splice Variants: A New Challenge for Atherosclerosis and Cancer-Targeted Therapies

    Science.gov (United States)

    Rizzacasa, Barbara; Morini, Elena; Pucci, Sabina; Murdocca, Michela; Novelli, Giuseppe; Amati, Francesca

    2017-01-01

    Alternative splicing (AS) is a process in which precursor messenger RNA (pre-mRNA) splicing sites are differentially selected to diversify the protein isoform population. Changes in AS patterns have an essential role in normal development, differentiation and response to physiological stimuli. It is documented that AS can generate both “risk” and “protective” splice variants that can contribute to the pathogenesis of several diseases including atherosclerosis. The main endothelial receptor for oxidized low-density lipoprotein (ox-LDLs) is LOX-1 receptor protein encoded by the OLR1 gene. When OLR1 undergoes AS events, it generates three variants: OLR1, OLR1D4 and LOXIN. The latter lacks exon 5 and two-thirds of the functional domain. Literature data demonstrate a protective role of LOXIN in pathologies correlated with LOX-1 overexpression such as atherosclerosis and tumors. In this review, we summarize recent developments in understanding of OLR1 AS while also highlighting data warranting further investigation of this process as a novel therapeutic target. PMID:28146073

  6. Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation?

    Science.gov (United States)

    Baron, Morgane; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne

    2012-07-01

    Cardiovascular diseases remain an important cause of morbi-mortality. Atherosclerosis, which predisposes to cardiovascular disorders such as myocardial infarction and stroke, develops silently over several decades. Identification of circulating biomarkers to evaluate cardiovascular event risk and pathology prognosis is of particular importance. Microparticles (MPs) are small vesicles released from cells upon apoptosis or activation. Microparticles are present in blood of healthy individuals. Studies showing a modification of their concentrations in patients with cardiovascular risk factors and after cardiovascular events identify MPs as potential biomarkers of disease. Moreover, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological compounds, used in the treatment of cardiovascular disease, can reduce plasma MP concentrations. Nevertheless, numerous issues remain to be solved before MP measurement can be applied as routine biological tests to improve cardiovascular risk prediction. In particular, prospective studies to identify the predictive values of MPs in pathologies such as cardiovascular diseases are needed to demonstrate whether MPs are useful biomarkers for the early detection of the disease and its progression. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  7. Development of biochip for risk factors of atherosclerosis

    International Nuclear Information System (INIS)

    Lee, Ki Teak; Lee, Jeung Hee; Bae, Sung Kyun; Lee, Cho Rong; Jun, Mi Sun

    2010-05-01

    Establishment of the detection technology on vascular disease and relative risk factors through measuring the activity of Lp-PLA2 in blood using [ 3 H]plateletactivating factor(PAF,1-O-alkyl-2-[ 3 H-acetyl]-sn-glycero-3-phospho choline) labeled by radioactive isotope

  8. Sustainable Development under Population Pressure: Lessons from Developed Land Consumption in the Conterminous U.S.

    Science.gov (United States)

    2015-01-01

    Population growth will result in a significant anthropogenic environmental change worldwide through increases in developed land (DL) consumption. DL consumption is an important environmental and socioeconomic process affecting humans and ecosystems. Attention has been given to DL modeling inside highly populated cities. However, modeling DL consumption should expand to non-metropolitan areas where arguably the environmental consequences are more significant. Here, we study all counties within the conterminous U.S. and based on satellite-derived product (National Land Cover Dataset 2001) we calculate the associated DL for each county. By using county population data from the 2000 census we present a comparative study on DL consumption and we propose a model linking population with expected DL consumption. Results indicate distinct geographic patterns of comparatively low and high consuming counties moving from east to west. We also demonstrate that the relationship of DL consumption with population is mostly linear, altering the notion that expected population growth will have lower DL consumption if added in counties with larger population. Added DL consumption is independent of a county’s starting population and only dependent on whether the county belongs to a Metropolitan Statistical Area (MSA). In the overlapping MSA and non-MSA population range there is also a constant DL efficiency gain of approximately 20km2 for a given population for MSA counties which suggests that transitioning from rural to urban counties has significantly higher benefits in lower populations. In addition, we analyze the socioeconomic composition of counties with extremely high or low DL consumption. High DL consumption counties have statistically lower Black/African American population, higher poverty rate and lower income per capita than average in both NMSA and MSA counties. Our analysis offers a baseline to investigate further land consumption strategies in anticipation of growing

  9. Platelets and their chemokines in atherosclerosis – clinical applications

    Directory of Open Access Journals (Sweden)

    Philipp evon Hundelshausen

    2014-08-01

    Full Text Available The concept of platelets as important players in the process of atherogenesis has become increasingly accepted due to accumulating experimental and clinical evidence. Despite the progress in understanding the molecular details of atherosclerosis, particularly by using animal models, the inflammatory and thrombotic roles of activated platelet s especially in the human system remain difficult to dissect, as often only the complications of atherosclerosis i.e. stroke and myocardial infarction are definable but not the plaque burden.Platelet indices including platelet count and mean platelet volume and soluble mediators released by activated platelets are associated with atherosclerosis. The chemokine CXCL4 has multiple atherogenic activities e.g. altering the differentiation of T cells and macrophages by inhibiting neutrophil and monocyte apoptosis and by increasing the uptake of oxLDL and synergizing with CCL5. CCL5 is released and deposited on endothelium by activated platelets thereby triggering atherogenic monocyte recruitment, which can be attenuated by blocking the corresponding chemokine receptor CCR5. Atheroprotective and plaque stabilizing properties are attributed to CXCL12, which plays an important role in regenerative processes by attracting progenitor cells. Its release from luminal attached platelets accelerates endothelial healing after injury. Platelet surface molecules GPIIb/IIIa, GP1bα, P-selectin, JAM-A and the CD40/CD40L dyade are crucially involved in the interaction with endothelial cells, leukocytes and matrix molecules affecting atherogenesis. Beyond the effects on the arterial inflammatory infiltrate, platelets affect cholesterol metabolism by binding, modifying and endocytosing LDL particles via their scavenger receptors and contribute to the formation of lipid laden macrophages. Current medical therapies for the prevention of atherosclerotic therapies enable the elucidation of mechanisms linking platelets to inflammation

  10. Intermittent hypoxia and hypercapnia induce pulmonary artery atherosclerosis and ventricular dysfunction in low density lipoprotein receptor deficient mice.

    Science.gov (United States)

    Douglas, Robert M; Bowden, Karen; Pattison, Jennifer; Peterson, Alexander B; Juliano, Joseph; Dalton, Nancy D; Gu, Yusu; Alvarez, Erika; Imamura, Toshihiro; Peterson, Kirk L; Witztum, Joseph L; Haddad, Gabriel G; Li, Andrew C

    2013-12-01

    Patients with obstructive sleep apnea, who experience episodic hypoxia and hypercapnia during sleep, often demonstrate increased inflammation, oxidative stress, and dyslipidemia. We hypothesized that sleep apnea patients would be predisposed to the development of atherosclerosis. To dissect the mechanisms involved, we developed an animal model in mice whereby we expose mice to intermittent hypoxia/hypercapnia (IHH) in normobaric environments. Two- to three-month-old low-density lipoprotein receptor deficient (Ldlr(-/-)) mice were fed a high-fat diet for 8 or 16 wk while being exposed to IHH for either 10 h/day or 24 h/day. Plasma lipid levels, pulmonary artery and aortic atherosclerotic lesions, and cardiac function were then assayed. Surprisingly, atherosclerosis in the aorta of IHH mice was similar compared with controls. However, in IHH mice, atherosclerosis was markedly increased in the trunk and proximal branches of the pulmonary artery of exposed mice; even though plasma cholesterol and triglycerides were lower than in controls. Hemodynamic analysis revealed that right ventricular maximum pressure and isovolumic relaxation constant were significantly increased in IHH exposed mice and left ventricular % fractional shortening was reduced. In conclusion, 1) Intermittent hypoxia/hypercapnia remarkably accelerated atherosclerotic lesions in the pulmonary artery of Ldlr(-/-) mice and 2) increased lesion formation in the pulmonary artery was associated with right and left ventricular dysfunction. These findings raise the possibility that patients with obstructive sleep apnea may be susceptible to atherosclerotic disease in the pulmonary vasculature, an observation that has not been previously recognized.

  11. Subclinical coronary atherosclerosis and neighbourhood deprivation in an urban region

    International Nuclear Information System (INIS)

    Dragano, Nico; Hoffmann, Barbara; Stang, Andreas; Moebus, Susanne; Verde, Pablo E.; Weyers, Simone; Moehlenkamp, Stefan; Schmermund, Axel; Mann, Klaus; Joeckel, Karl-Heinz; Erbel, Raimund; Siegrist, Johannes

    2009-01-01

    Inhabitants of deprived neighbourhoods are at higher risk of coronary heart disease. In this study we investigate the hypothesis that social inequalities at neighbourhood level become already manifest in subclinical coronary atherosclerosis, as defined by electron-beam computed tomography derived measures. Coronary artery calcification was assessed as a marker of atherosclerosis in a population based sample of 4301 men and women (45-75 years) without a history of coronary heart disease. Participants lived in three adjacent cities in Germany and were examined between 2000 and 2003 as part of the Heinz Nixdorf Recall Study. Individual level data was combined with neighbourhood level information about unemployment, welfare and living space per inhabitant. This dataset was analysed with descriptive and multilevel regression methods. An association between neighbourhood deprivation and subclinical coronary calcification was observed. After adjustment for age and individual socioeconomic status male inhabitants of high unemployment neighbourhoods had an odds ratio of 1.45 (1.11, 1.96) of exhibiting a high calcification score (>75th percentile) compared to men living in low unemployment areas. The respective odds for women was 1.29 (0.97, 1.70). Additional explorative analyses suggest that clustering of unhealthy lifestyles in deprived neighbourhoods contributes to the observed association. In conclusion, findings suggest that certain neighbourhood characteristics promote the emergence of coronary atherosclerosis. This might point to a pathway from neighbourhood deprivation to manifest coronary heart disease

  12. Biomarkers of Subclinical Atherosclerosis in Patients with Autoimmune Disorders

    Directory of Open Access Journals (Sweden)

    Elisabetta Profumo

    2012-01-01

    Full Text Available Atherosclerosis is accelerated in rheumatoid arthritis (RA and psoriatic arthritis (PsA. We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs, nitric oxide (NO, 3-nitrotyrosine, vitamin A, vitamin E, and β-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of β-carotene in patients with RA and PsA than in controls. β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders.

  13. Prediabetes is not a risk factor for subclinical coronary atherosclerosis.

    Science.gov (United States)

    Park, Gyung-Min; Cho, Young-Rak; Lee, Seung-Whan; Yun, Sung-Cheol; Won, Ki-Bum; Ann, Soe Hee; Kim, Yong-Giun; Kim, Shin-Jae; Roh, Jae-Hyung; Kim, Young-Hak; Yang, Dong Hyun; Kang, Joon-Won; Lim, Tae-Hwan; Jung, Chang Hee; Koh, Eun Hee; Lee, Woo Je; Kim, Min-Seon; Lee, Ki-Up; Park, Joong-Yeol; Kim, Hong-Kyu; Choe, Jaewon; Lee, Sang-Gon

    2017-09-15

    There are limited data regarding the influence of glycemic status on the risk of subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals. We analyzed 6434 asymptomatic individuals who underwent CCTA. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. Of study participants, 2197 (34.1%), 3122 (48.5%), and 1115 (17.3%) were categorized as normal, prediabetic and diabetic individuals, respectively. Compared with normal individuals, there were no statistically differences in the adjusted odds ratios of prediabetic individuals for significant coronary artery stenosis (0.98, 95% confidence interval [CI] 0.80-1.22, p=0.888), any plaque (0.96, 95% CI 0.86-1.07, p=0.483), calcified plaque (0.90, 95% CI 0.79-1.01, p=0.080), non-calcified plaque (1.02, 95% CI 0.88-1.17, p=0.803), and mixed plaque (1.00, 95% CI 0.82-1.22, p=0.983). However, adjusted odds ratios for significant coronary artery stenosis (1.71, 95% CI 1.34-2.19, pprediabetic individuals were not associated with an increased risk of subclinical coronary atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Flow-mediated lipoprotein retention; Pregnancy-associated plasma protein-A inhibition in atherosclerosis and its release during myocardial ischemia

    DEFF Research Database (Denmark)

    Steffensen, Lasse Bach

    , which states that retention of lipoproteins is the key initiating event of atherosclerosis development. Pregnancy-associated plasma protein-A (PAPP-A) regulates the insulin-like growth factor (IGF) system by proteolytic cleavage of a subset of IGF-binding proteins. Studies in mice have established PAPP...

  15. Energetic materials research and development activities at Sandia National Laboratories supported under DP-10 programs

    Energy Technology Data Exchange (ETDEWEB)

    Ratzel, A.C. III

    1998-09-01

    This report provides summary descriptions of Energetic Materials (EM) Research and Development activities performed at Sandia National Laboratories and funded through the Department of Energy DP-10 Program Office in FY97 and FY98. The work falls under three major focus areas: EM Chemistry, EM Characterization, and EM Phenomenological Model Development. The research supports the Sandia component mission and also Sandia's overall role as safety steward for the DOE Nuclear Weapons Complex.

  16. Financial development under the shade of globalization and financial institutions : the case of Pakistan

    OpenAIRE

    Muhammad Shahbaz; Akhtar Lodhi; Muhammad Sabihuddin Butt

    2007-01-01

    This study investigates the importance of financial institutions, net capital inflows, and trade openness for financial-sector development in a small developing economy like Pakistan. Two approaches (Johansen test and autoregressive distributive lag approach) were employed for the robustness of long-run relationships among the variables under consideration and found that both techniques provide robust results for long-run relationships, in Pakistan’s case. Net capital in inflows has positive ...

  17. Seeking alternatives to probit 9 when developing treatments for wood packaging materials under ISPM No. 15

    Science.gov (United States)

    R.A. Haack; A. Uzunovic; K. Hoover; J.A. Cook

    2011-01-01

    ISPM No. 15 presents guidelines for treating wood packaging material used in international trade. There are currently two approved phytosanitary treatments: heat treatment and methyl bromide fumigation. New treatments are under development, and are needed given that methyl bromide is being phased out. Probit 9 efficacy (100% mortality of at least 93 613 test organisms...

  18. Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor

    DEFF Research Database (Denmark)

    Hu, Jie Hong; Touch, Phanith; Zhang, Jingwan

    2015-01-01

    -accelerated atherosclerosis) to investigate whether systemic inhibition of proteolytic activity of uPA or a subset of MMPs can reduce protease-induced atherosclerosis and aortic dilation. METHODS AND RESULTS: SR-uPA mice were fed a high-fat diet for 10 weeks and treated either with an antibody inhibiting mouse uPA (mU1...... surface lesion coverage. Several lines of evidence identified MMP-13 as a mediator of uPA-induced aortic MMP activity. CONCLUSIONS: Pharmacological inhibition of either uPA or selected MMPs decreased atherosclerosis in SR-uPA mice. uPA inhibition decreased aortic dilation. Differential effects of both...... agents on aortic root vs. distal aortic atherosclerosis suggest prevention of atherosclerosis progression vs. initiation. Systemic inhibition of uPA or a subset of MMPs shows promise for treating atherosclerosis....

  19. EFFECT OF DIETARY OLIVE OIL/CHOLESTEROL ON SERUM LIPOPROTEINS, LIPID PEROXIDATION, AND ATHEROSCLEROSIS IN RABBITS

    Directory of Open Access Journals (Sweden)

    R MAHDAVI

    2003-03-01

    Full Text Available Introduction: High plasma cholesterol levels, mainly LDL are a widely recognized major risk factor for Coronary Heart Disease (CHD. According to the epidemiologic studies findings, people from the Mediterranean countries, have lower CHD rats than other countries, in these countries usual diet is high in olive oil. The present study compares the effects of cholesterol enriched diet with or without adding olive oil on serum Lipoproteins, lipid per oxidation, and atherosclerosis development. Method: Twenty Dutch male rabbits were Categorized to four groups (one group as Control, and others as Experimental. They received one of standard, cholesterol - rich, olive oil rich and combined (cholesterol + olive oil diet for Twelve weeks. Fasting blood samples from heart were collected at the beginning, and the end of Experimental period. Means of total cholesterol, HDL-Ctriglycerides, MDA and antioxidant caperimental period, significant differences were showed in total cholesterol, HDL-C, triglyceride and MDA between groups. Results: The comparison of cholesterol rich diet with cholesterol + olive oil showed a higher mean of MDA in cholesterol rich group (P < 0.001. Biochemical factors and aortic lesion degree showed no significant difference between standard and olive oil group. Aortic lesions in cholesterol + olive oil showed nonsignificant lower degree than cholesterol group. Discussion: This findings showed preventive effect of olive oil against atherosclerosis which is independent of plasma lipoprotein effect, and suggested that probably olive oil acts on arteries directly.

  20. Metoprolol Reduces Proinflammatory Cytokines and Atherosclerosis in ApoE−/− Mice

    Directory of Open Access Journals (Sweden)

    Marcus A. Ulleryd

    2014-01-01

    Full Text Available A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE−/− mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE−/− mice were treated with metoprolol (2.5 mg/kg/h or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P<0.05 versus Control. Further, metoprolol reduced serum TNFα and the chemokine CXCL1 (P<0.01 versus Control for both as well as decreasing the macrophage content in the plaques (P<0.01 versus Control. Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE−/− mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNFα and CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect.

  1. Therapeutic modulation of the natural history of coronary atherosclerosis: lessons learned from serial imaging studies.

    Science.gov (United States)

    Andrews, Jordan; Puri, Rishi; Kataoka, Yu; Nicholls, Stephen J; Psaltis, Peter J

    2016-08-01

    Despite advances in risk prediction, preventive and therapeutic strategies, atherosclerotic cardiovascular disease remains a major public health challenge worldwide, carrying considerable morbidity, mortality and health economic burden. There continues to be a need to better understand the natural history of this disease to guide the development of more effective treatment, integral to which is the rapidly evolving field of coronary artery imaging. Various imaging modalities have been refined to enable detailed visualization of the pathological substrate of atherosclerosis, providing accurate and reproducible measures of coronary plaque burden and composition, including the presence of high-risk characteristics. The serial application of such techniques, including coronary computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have uncovered important insights into the progression of coronary plaque over time in patients with stable and unstable coronary artery disease (CAD), and its responsiveness to therapeutic interventions. Here we review the use of different imaging modalities for the surveillance of coronary atherosclerosis and the lessons they have provided about the modulation of CAD by both traditional and experimental therapies.

  2. Endothelial dysfunction and atherosclerosis in children with irreversible pulmonary hypertension due to congenital heart disease

    International Nuclear Information System (INIS)

    Çiftel, Murat; Şimşek, Ayse; Turan, Özlem; Kardelen, Firat; Akçurin, Gayaz; Ertuğ, Halil

    2012-01-01

    To assess endothelial dysfunction and the risk for coronary atherosclerosis in children with irreversible pulmonary hypertension due to congenital heart disease (CHD). The study included 18 cyanotic patients (the mean age was 12.28 ± 3.26 years) who developed irreversible pulmonary hypertension due to cyanotic and acyanotic CHDs, and 18 control patients (the mean age was 11.78 ± 3.00 years). Study groups were compared for flow-mediated dilatation (FMD), carotid intima media thickness (CIMT) and atherosclerotic risk factors. Compared to the control group, the mean FMD was significantly reduced in the cyanotic group (5.26 ± 2.42% and 9.48 ± 2.60%, respectively; P-value < 0.001). No significant difference was observed between the groups in CIMT (0.41 ± 0.08 mm and 0.39 ± 0.06 mm, respectively; P-value = 0.299). The levels of total cholesterol, low-density lipoprotein–cholesterol and very low-density lipoprotein–cholesterol were statistically significantly lower compared tothe control group (P-value = 0.001, 0.006 and 0.014, respectively), whereas no statistically significant difference was found in the levels of high-density lipoprotein–cholesterol and triglycerides (P-value = 0.113 and 0.975, respectively). Systemic endothelial dysfunction in children with irreversible pulmonary hypertension due to CHD was noted but there was no increased risk for atherosclerosis

  3. The everyday lives of video game developers: Experimentally understanding underlying systems/structures

    Directory of Open Access Journals (Sweden)

    Casey O'Donnell

    2009-03-01

    Full Text Available This essay examines how tensions between work and play for video game developers shape the worlds they create. The worlds of game developers, whose daily activity is linked to larger systems of experimentation and technoscientific practice, provide insights that transcend video game development work. The essay draws on ethnographic material from over 3 years of fieldwork with video game developers in the United States and India. It develops the notion of creative collaborative practice based on work in the fields of science and technology studies, game studies, and media studies. The importance of, the desire for, or the drive to understand underlying systems and structures has become fundamental to creative collaborative practice. I argue that the daily activity of game development embodies skills fundamental to creative collaborative practice and that these capabilities represent fundamental aspects of critical thought. Simultaneously, numerous interests have begun to intervene in ways that endanger these foundations of creative collaborative practice.

  4. The System-Synergetic Approach to Development of Banking Systems under Conditions of Financial Instability

    Directory of Open Access Journals (Sweden)

    Karcheva Ganna T.

    2015-03-01

    Full Text Available The aim of the article is to study the theoretical and practical aspects of using the system-synergetic approach to the development and functioning of banking systems under conditions of financial instability. It has been grounded that the theoretical foundations for the development of banking systems are based on the system approach, according to which the banking systems belong to a class of special complex dynamic, self-motivated and open systems with an integrated structure of subsystems and functions. The study of such systems should include two aspects — system-cybernetic and system-synergetic ones. It has been proved that under stationary conditions the banking system development goes on in accordance with the systemcybernetic model, which suggests the presence of a management subsystem, which functions are performed by the central bank. Under conditions of financial instability, in the pre-crisis, crisis and post-crisis periods to study the development of banking systems the system-synergetic approach taking into account the multi-variant and alternative development of the banking system at bifurcation points is used. The criteria of the banking system entering the phase of bifurcation based on assessing the volatility of the current liabilities and possibility of building an analytical trend have been determined. The methodical approaches to evaluating the synergistic effects and level of financial stability of the banking system have been suggested, experimental calculations have been made.

  5. Development of the model for the stress calculation of fuel assembly under accident load

    International Nuclear Information System (INIS)

    Kim, Il Kon

    1993-01-01

    The finite element model for the stress calculation in guide thimbles of a fuel assembly (FA) under seismic and loss-of-coolant-accident (LOCA) load is developed. For the stress calculation of FA under accident load, at first the program MAIN is developed to select the worst bending mode shaped FA from core model. And then the model for the stress calculation of FA is developed by means of the finite element code. The calculated results of program MAIN are used as the kinematic constraints of the finite element model of a FA. Compared the calculated results of the stiffness of the finite element model of FA with the test results they have good agreements. (Author)

  6. Polymicrobial infection with major periodontal pathogens induced periodontal disease and aortic atherosclerosis in hyperlipidemic ApoE(null mice.

    Directory of Open Access Journals (Sweden)

    Mercedes F Rivera

    Full Text Available Periodontal disease (PD and atherosclerosis are both polymicrobial and multifactorial and although observational studies supported the association, the causative relationship between these two diseases is not yet established. Polymicrobial infection-induced periodontal disease is postulated to accelerate atherosclerotic plaque growth by enhancing atherosclerotic risk factors of orally infected Apolipoprotein E deficient (ApoE(null mice. At 16 weeks of infection, samples of blood, mandible, maxilla, aorta, heart, spleen, and liver were collected, analyzed for bacterial genomic DNA, immune response, inflammation, alveolar bone loss, serum inflammatory marker, atherosclerosis risk factors, and aortic atherosclerosis. PCR analysis of polymicrobial-infected (Porphyromonas gingivalis [P. gingivalis], Treponema denticola [T. denticola], and Tannerella forsythia [T. forsythia] mice resulted in detection of bacterial genomic DNA in oral plaque samples indicating colonization of the oral cavity by all three species. Fluorescent in situ hybridization detected P. gingivalis and T. denticola within gingival tissues of infected mice and morphometric analysis showed an increase in palatal alveolar bone loss (p<0.0001 and intrabony defects suggesting development of periodontal disease in this model. Polymicrobial-infected mice also showed an increase in aortic plaque area (p<0.05 with macrophage accumulation, enhanced serum amyloid A, and increased serum cholesterol and triglycerides. A systemic infection was indicated by the detection of bacterial genomic DNA in the aorta and liver of infected mice and elevated levels of bacterial specific IgG antibodies (p<0.0001. This study was a unique effort to understand the effects of a polymicrobial infection with P. gingivalis, T. denticola and T. forsythia on periodontal disease and associated atherosclerosis in ApoE(null mice.

  7. Life quality and living standards in big cities under conditions of high-rise construction development

    Science.gov (United States)

    Avdeeva, Elena; Averina, Tatiana; Kochetova, Larisa

    2018-03-01

    Modern urbanization processes occurring on a global scale inevitably lead to an increase in population density in large cities. People assess the state of life quality and living standards of megalopolises under conditions of high-rise construction development ambiguously. Using SWOT analysis, the authors distinguished positive and negative aspects of high-rise construction, highlighted threats to its development and its opportunities. The article considers the model of development of the city's industry and infrastructure, which enables determining the optimal volume of production by sectors and branches of city economy in order to increase its innovative, production and economic potential and business activity.

  8. The impact of omega 3 fatty acids in atherosclerosis and arterial stiffness: An overview of their actions.

    Science.gov (United States)

    Verveniotis, Alexios; Siasos, Gerasimos; Oikonomou, Evangelos; Tsigkou, Vasiliki; Papageorgiou, Nikolaos; Zaromitidou, Marina; Psaltopoulou, Theodora; Marinos, Georgios; Deftereos, Spyridon; Vavuranakis, Manolis; Stefanadis, Christodoulos; Papavassiliou, Athanasios G; Tousoulis, Dimitris

    2018-03-20

    Fatty acids are common dietary nutrients particularly in economically developed countries. Research has revealed that omega-3fatty acids exert beneficial effects in the progression of atherosclerosis and cardiovascular disease. Moreover, eicosapentaenoic acid and docosahexaenoic acid possess a number of biological actions which improve cardio-metabolic health. Omega-3 fatty acids display remarkable anti-oxidant, anti-inflammatory, anti-thrombotic and anti-arrythmogenic actions. Furthermore, they improve the levels of triglycerides, glucose metabolism and endothelial function. The aim of this review article is to present physical, biochemical and biological properties of omega-3 fatty acids and summarize the most important mechanisms of action on arterial wall properties and arterial stiffness in atherosclerosis. Omega-3 fatty acids may prevent the progression of atherosclerosis. Endothelial dysfunction and arterial stiffness can be regulated by the supplementation of omega-3 fatty acids. The mechanisms of action of omega-3 fatty acids on cardiovascular health and arterial stiffening have been established. However, further research is needed in order to translate the conflicting results among the studies and improve the therapeutic options of cardiovascular disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Correlation of collagen synthesis with polarization-sensitive optical coherence tomography imaging of in vitro human atherosclerosis

    Science.gov (United States)

    Kuo, Wen-Chuan; Shyu, Jeou-Jong; Chou, Nai-Kuan; Lai, Chih-Ming; Tien, En-Kuang; Huang, Huan-Jang; Chou, Chien; Jan, Gwo-Jen

    2005-04-01

    Atherosclerosis is unquestionably the leading cause of morbidity and mortality in developed countries. In the mean time, the worldwide importance of acute vascular syndromes is increasing. Because collagen fiber is a critical component of atherosclerotic lesions; it constitutes up to 60% of the total atherosclerotic plaque protein. The uncontrolled collagen accumulation leads to arterial stenosis, whereas excessive collagen breakdown weakens plaques thereby making them prone to rupture finally. Thus, in this study, we present the first application, to our knowledge, of using polarization-sensitive optical coherence tomography (PS-OCT) in human atherosclerosis. We demonstrate this technique for imaging of intensity, birefringence, and fast-axis orientation simultaneously in atherosclerotic plaques. This in vitro study suggests that the birefringence change in plaque is due to the prominent deposition of collagen according to the correlation of PS-OCT images with histological counterpart. Moreover, we can acquire quantitative criteria based on the change of polarization of incident beam to estimate whether the collagen synthesized is "too much" or "not enough". Thus by combining of high resolution intensity imaging and birefringence detection makes PS-OCT could be a potentially powerful tool for early assessment of atherosclerosis appearance and the prediction of plaque rupture in clinic.

  10. The association of ABO blood groups with extent of coronary atherosclerosis in Croatian patients suffering from chronic coronary artery disease.

    Science.gov (United States)

    Karabuva, Svjetlana; Carević, Vedran; Radić, Mislav; Fabijanić, Damir

    2013-01-01

    The aim of study was to: 1) examine the relationship between ABO blood groups and extent of coronary atherosclerosis in patients with chronic coronary artery disease (CAD), 2) compare ABO blood groups distribution in CAD patients and general population, 3) examine possible differences in traditional risk factors frequency in CAD patients with different ABO blood groups. In the 646 chronic CAD patients (72.4% males) coronary angiograms were scored by quantitative assessment using multiple angiographic scoring system, Traditional risk factors were self reported or measured by standard methods. ABO blood distribution of patients was compared with group of 651 healthy blood donors (74.6% males). Among all ABO blood group patients there was no significant difference between the extent of coronary atherosclerosis with regard to all the three scoring systems: number of affected coronary arteries (P = 0.857), Gensini score (P = 0.818), and number of segments narrowed > 50% (P = 0.781). There was no significant difference in ABO blood group distribution between CAD patients and healthy blood donors. Among CAD patients, men with blood group AB were significantly younger than their pairs with non-AB blood groups (P = 0.008). Among CAD patients with AB blood group, males groups (P = 0.003). No association between ABO blood groups and the extent of coronary atherosclerosis in Croatian CAD patients is observed. Observation that AB blood group might possibly identify Croatian males at risk to develop the premature CAD has to be tested in larger cohort of patients.

  11. Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Rena Watanabe

    2018-02-01

    Full Text Available Tumor necrosis factor-stimulated gene-6 (TSG-6 is a 35-kDa glycoprotein that has been shown to exert anti-inflammatory effects in experimental models of arthritis, acute myocardial infarction, and acute cerebral infarction. Several lines of evidence have shed light on the pathophysiological roles of TSG-6 in atherosclerosis. TSG-6 suppresses inflammatory responses of endothelial cells, neutrophils, and macrophages as well as macrophage foam cell formation and vascular smooth muscle cell (VSMC migration and proliferation. Exogenous TSG-6 infusion and endogenous TSG-6 attenuation with a neutralizing antibody for four weeks retards and accelerates, respectively, the development of aortic atherosclerotic lesions in ApoE-deficient mice. TSG-6 also decreases the macrophage/VSMC ratio (a marker of plaque instability and promotes collagen fibers in atheromatous plaques. In patients with coronary artery disease (CAD, plasma TSG-6 levels are increased and TSG-6 is abundantly expressed in the fibrous cap within coronary atheromatous plaques, indicating that TSG-6 increases to counteract the progression of atherosclerosis and stabilize the plaque. These findings indicate that endogenous TSG-6 enhancement and exogenous TSG-6 replacement treatments are expected to emerge as new lines of therapy against atherosclerosis and related CAD. Therefore, this review provides support for the clinical utility of TSG-6 in the diagnosis and treatment of atherosclerotic cardiovascular diseases.

  12. PECAM-1 gene polymorphism (rs668 and subclinical markers of carotid atherosclerosis in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Popović D

    2016-06-01

    Full Text Available The platelet endothelial cell adhesion molecule 1 (PECAM-1 plays an important role in many inflammatory processes, including the development of atherosclerosis. Polymorphism rs668 of the PECAM-1 gene (373C/G is functional, and it was reported to be associated with increased serum levels of PECAM-1. We investigated the association between the rs668 polymorphism of PECAM-1 and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM. Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT and plaque characteristics (presence and structure were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Geno-typing of the PECAM-1 gene polymorphism (rs668 was performed using KASPar assays. The control examinations were performed 3.8 ± 0.5 years after the initial examination. Higher CIMT was found in patients with T2DM in comparison with subjects without T2DM. Statistically sig-nificantly faster progression of the atherosclerotic markers was shown in subjects with T2DM in comparison with the control group. When adjusted to other risk factors, the rs668 GG genotype was associated with an increased risk of carotid plaques in subjects with T2DM. We concluded that our study demonstrated a minor effect of the rs668 PECAM-1 on markers of carotid atherosclerosis in subjects with T2DM.

  13. Atherosclerosis profile and incidence of cardiovascular events: a population-based survey

    Directory of Open Access Journals (Sweden)

    Bullano Michael F

    2009-09-01

    Full Text Available Abstract Background Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals. Methods Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization. Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events. Results Of 17,640 respondents, 488 (2.8% reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2 [all p Conclusion Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.

  14. [25 year experience with using surgical correction of dislipidemia in treatment of patients with atherosclerosis].

    Science.gov (United States)

    Sedov, V M; Mirchuk, K K; Sedletskiĭ, Iu I

    2011-01-01

    An analysis of results of using partial ileoshunting for the treatment of dislipidemia in 159 patients with atherosclerosis has shown that operation of partial ileoshunting has an obligatory, pronounced and lifelong lipidcorrecting effect. An antiatherogenic effect of the operation of partial ileoshunting is manifested as the improvement of the clinical course of the disease caused by atherosclerosis, by less number of thrombotic complications of atherosclerosis and less lethality from cardio-vascular diseases. At a longer follow-up period, the efficiency of partial ileoshunting as a means of secondary prophylactics of atherosclerosis is confirmed but in case of liquidation after operation of dislipoproteidemia.

  15. Analysis on the development of scientific and technical information under new competitive environment

    International Nuclear Information System (INIS)

    Li Tao

    2010-01-01

    The current external environment of information work has undergone profound changes. The world competition in Military fields, the development of national economy and the applications of high-technologies put forward higher requirements to intelligence work. Under the environment of global information integration, 'eyes and ears' roles of nuclear scientific and technical information will be more highlighted. In this context, we believe that the way of nuclear sci-tech information development should be focused on comprehensive research and be based on the building of information resources and advanced information technology methods, forming an integrated service system with capabilities of rapid resources, decision support, information assurance and sustainable development. The goal of nuclear sci-tech information development should be to serve the development of nuclear power and the popularization and application of nuclear technology in the fields of national economy, to implement the strategy of 'integrated intelligence support', to ensure the formatio