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Sample records for atherosclerotic plaque development

  1. Chemokine Receptor 7 Knockout Attenuates Atherosclerotic Plaque Development

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

  3. Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

    Directory of Open Access Journals (Sweden)

    Eugenio Picano

    2015-05-01

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

  4. Nuclear Molecular Imaging for Vulnerable Atherosclerotic Plaques

    OpenAIRE

    Lee, Soo Jin; Paeng, Jin Chul

    2015-01-01

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

  5. Quantitative Evaluation of the Polarization Characteristics of Coronary Arteries Atherosclerotic Plaques at Different Development Stages

    Directory of Open Access Journals (Sweden)

    E.V. Gubarkova

    2015-12-01

    Full Text Available The aim of the investigation was to develop an approach to quantitative evaluation of polarization properties (birefringence and cross-scattering basing on cross-polarization OCT images (CP OCT in order to characterize the development stages of atherosclerotic plaques and to reveal unstable ones. Materials and Methods. We report on quantitative analysis of CP OCT images of the seven development stages of atherosclerotic plaques ex vivo. Integral depolarization factor (IDF and effective birefringence coefficient (Δn were proposed as parameters for quantitative characterization of the CP OCT images. Results. Calculation of the IDF and Δn in the local region of interest (intima/fibrous cap showed a statistically relevant difference between stable (stage IV and unstable (stage Va plaques (0.46±0.21 against 0.09±0.04 for IDF and (0.47±0.10·10–3 against (0.25±0.07·10–3 for Δn; (p<0.05. It was found that Δn value in the range (0.22–0.29·10–3 (within the limits of two standard deviations indicates the presence of only a small amount of highly organized collagen in the fibrous cap of an unstable plaque which can indicate its tendency to rupture. We believe that these changes are connected with the prevalence of disorganized fibers during the inflammatory process in the fibrous cap of an unstable plaque, and to the presence of clusters of foam cells and inflammatory cells between them. Conclusion. The proposed approach to the quantitative evaluation of CP OCT images (calculation of IDF and building Δn maps allows to assess both cross-scattering and birefringence of atherosclerotic plaques at various development stages and more reliably reveal their vulnerability.

  6. Electrochemical Impedance Spectroscopy to Characterize Inflammatory Atherosclerotic Plaques

    OpenAIRE

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

    2011-01-01

    Despite advances in diagnosis and therapy, atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in the Western world. Predicting metabolically active atherosclerotic lesions has remained an unmet clinical need. We hereby developed an electrochemical strategy to characterize the inflammatory states of high-risk atherosclerotic plaques. Using the concentric bipolar microelectrodes, we sought to demonstrate distinct Electrochemical Impedance Spectroscopic (...

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

    Science.gov (United States)

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

    2010-01-01

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

  8. Ultrafast laser ablation for targeted atherosclerotic plaque removal

    Science.gov (United States)

    Lanvin, Thomas; Conkey, Donald B.; Descloux, Laurent; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

    2015-07-01

    Coronary artery disease, the main cause of heart disease, develops as immune cells and lipids accumulate into plaques within the coronary arterial wall. As a plaque grows, the tissue layer (fibrous cap) separating it from the blood flow becomes thinner and increasingly susceptible to rupturing and causing a potentially lethal thrombosis. The stabilization and/or treatment of atherosclerotic plaque is required to prevent rupturing and remains an unsolved medical problem. Here we show for the first time targeted, subsurface ablation of atherosclerotic plaque using ultrafast laser pulses. Excised atherosclerotic mouse aortas were ablated with ultrafast near-infrared (NIR) laser pulses. The physical damage was characterized with histological sections of the ablated atherosclerotic arteries from six different mice. The ultrafast ablation system was integrated with optical coherence tomography (OCT) imaging for plaque-specific targeting and monitoring of the resulting ablation volume. We find that ultrafast ablation of plaque just below the surface is possible without causing damage to the fibrous cap, which indicates the potential use of ultrafast ablation for subsurface atherosclerotic plaque removal. We further demonstrate ex vivo subsurface ablation of a plaque volume through a catheter device with the high-energy ultrafast pulse delivered via hollow-core photonic crystal fiber.

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

    Science.gov (United States)

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

    2016-12-01

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

  10. Controlling the angiogenic switch in developing atherosclerotic plaques: Possible targets for therapeutic intervention

    Directory of Open Access Journals (Sweden)

    Slevin Mark

    2009-09-01

    Full Text Available Abstract Plaque angiogenesis may have an important role in the development of atherosclerosis. Vasa vasorum angiogenesis and medial infiltration provides nutrients to the developing and expanding intima and therefore, may prevent cellular death and contribute to plaque growth and stabilization in early lesions. However in more advanced plaques, inflammatory cell infiltration, and concomitant production of numerous pro-angiogenic cytokines may be responsible for induction of uncontrolled neointimal microvessel proliferation resulting in production of immature and fragile neovessels similar to that seen in tumour development. These could contribute to development of an unstable haemorrhagic rupture-prone environment. Increasing evidence has suggested that the expression of intimal neovessels is directly related to the stage of plaque development, the risk of plaque rupture, and subsequently, the presence of symptomatic disease, the timing of ischemic neurological events and myocardial/cerebral infarction. Despite this, there is conflicting evidence regarding the causal relationship between neovessel expression and plaque thrombosis with some in vivo experimental models suggesting the contrary and as yet, few direct mediators of angiogenesis have been identified and associated with plaque instability in vivo. In recent years, an increasing number of angiogenic therapeutic targets have been proposed in order to facilitate modulation of neovascularization and its consequences in diseases such as cancer and macular degeneration. A complete knowledge of the mechanisms responsible for initiation of adventitial vessel proliferation, their extension into the intimal regions and possible de-novo synthesis of neovessels following differentiation of bone-marrow-derived stem cells is required in order to contemplate potential single or combinational anti-angiogenic therapies. In this review, we will examine the importance of angiogenesis in complicated plaque

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

    LENUS (Irish Health Repository)

    Maher, Eoghan

    2009-12-11

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

  12. Imaging Atherosclerotic Plaque Calcification: Translating Biology.

    Science.gov (United States)

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

    2016-08-01

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

  13. Hyperspectral imaging of atherosclerotic plaques in vitro

    Science.gov (United States)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Olstad, Elisabeth; Haugen, Olav A.; Aksnes, Astrid; Svaasand, Lars O.

    2011-02-01

    Vulnerable plaques constitute a risk for serious heart problems, and are difficult to identify using existing methods. Hyperspectral imaging combines spectral- and spatial information, providing new possibilities for precise optical characterization of atherosclerotic lesions. Hyperspectral data were collected from excised aorta samples (n = 11) using both white-light and ultraviolet illumination. Single lesions (n = 42) were chosen for further investigation, and classified according to histological findings. The corresponding hyperspectral images were characterized using statistical image analysis tools (minimum noise fraction, K-means clustering, principal component analysis) and evaluation of reflectance/fluorescence spectra. Image analysis combined with histology revealed the complexity and heterogeneity of aortic plaques. Plaque features such as lipids and calcifications could be identified from the hyperspectral images. Most of the advanced lesions had a central region surrounded by an outer rim or shoulder-region of the plaque, which is considered a weak spot in vulnerable lesions. These features could be identified in both the white-light and fluorescence data. Hyperspectral imaging was shown to be a promising tool for detection and characterization of advanced atherosclerotic plaques in vitro. Hyperspectral imaging provides more diagnostic information about the heterogeneity of the lesions than conventional single point spectroscopic measurements.

  14. Atherosclerotic plaque detection by confocal Brillouin and Raman microscopies

    Science.gov (United States)

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

    2015-02-01

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

  15. Increased ADRP expression in human atherosclerotic lesions correlates with plaque instability

    OpenAIRE

    Xu, Bin; Zhao, Huiying; Wang, Shengnan; Sun, Xiwei; Qin, Xiujiao

    2015-01-01

    Adipose differentiation-related protein (ADRP) is intrinsically associated with the surface of lipid droplets implicated in the development of atherosclerosis. We analyzed expression of ADRP in human popliteal artery plaques. Atherosclerotic plaque tissue from the popliteal artery was obtained from 18 patients undergoing lower extremity amputation for arteriosclerosis obliterans, and with either stable (n = 6) or unstable (n = 12) atherosclerotic plaques. Plaques were histologically classifie...

  16. Multimodality imaging of carotid atherosclerotic plaque: Going beyond stenosis

    OpenAIRE

    Divyata Hingwala; Chandrasekharan Kesavadas; Sylaja, Padmavathy N; Bejoy Thomas; Tirur Raman Kapilamoorthy

    2013-01-01

    Apart from the degree of stenosis, the morphology of carotid atherosclerotic plaques and presence of neovascularization are important factors that may help to evaluate the risk and ′vulnerability′ of plaques and may also influence the choice of treatment. In this article, we aim to describe the techniques and imaging findings on CTA, high resolution MRI and contrast enhanced ultrasound in the evaluation of carotid atherosclerotic plaques. We also discuss a few representative cases from our in...

  17. Atherosclerosis and Atheroma Plaque Rupture: Imaging Modalities in the Visualization of Vasa Vasorum and Atherosclerotic Plaques

    OpenAIRE

    2014-01-01

    Invasive angiography has been widely accepted as the gold standard to diagnose cardiovascular pathologies. Despite its superior resolution of demonstrating atherosclerotic plaque in terms of degree of lumen stenosis, the morphological assessment for the plaque is insufficient for the analysis of plaque components, and therefore, unable to predict the risk status or vulnerability of atherosclerotic plaque. There is an increased body of evidence to show that the vasa vasorum play an important r...

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

    OpenAIRE

    Wilensky, Robert L.; Shi, Yi; Mohler, Emile R; Hamamdzic, Damir; Burgert, Mark E.; Li, Jun; Postle, Anthony; Fenning, Robert S.; Bollinger, James G.; Hoffman, Bryan E; Pelchovitz, Daniel J.; Yang, Jisheng; Mirabile, Rosanna C; Webb, Christine L; Zhang, LeFeng

    2008-01-01

    Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is associated with increased risk of cardiac events, but it is not known whether Lp-PLA2 is a causative agent. Here we show that selective inhibition of Lp-PLA2 with darapladib reduced development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic swine. Darapladib markedly inhibited plasma and lesion Lp-PLA2 activity and reduced lesion lysophosphatidylcholine content. Analysis of coronary gene express...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    PURPOSE: Metabolic assessment of vascular inflammation by 2-[F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG)-PET is a promising new approach for the evaluation of the vulnerability of atherosclerotic plaques. Quantitative real-time PCR allows measurement of gene expression of markers...... of atherosclerotic plaque vulnerability. These techniques were applied in advanced atherosclerotic disease to relate metabolism and inflammatory activity to the gene expression profile of the vulnerable atherosclerotic plaque. METHODS: Seventeen patients with clinical symptoms of cerebral vascular...... subsequently recovered by carotid endarterectomy. The gene expression of markers of vulnerability - CD68, IL-18, matrix metalloproteinase 9, cathepsin K, GLUT-1, and hexokinase type II (HK2) - were measured in plaques by quantitative PCR. RESULTS: In a multivariate linear regression model, GLUT-1, CD68...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    microbes isolated from human atherosclerotic vessels. However, high-resolution investigation of microbial infectious agents from human vessels that may contribute to atherosclerosis is very limited. In spite of the progress in recent sequencing technologies, analyzing host-associated metagenomes remain...... a challenge. RESULTS: To investigate microbiome diversity within human atherosclerotic tissue samples, we employed high-throughput metagenomic analysis on: (1) atherosclerotic plaques obtained from a group of patients who underwent endarterectomy due to recent transient cerebral ischemia or stroke. (2...

  1. Atherosclerosis and Atheroma Plaque Rupture: Imaging Modalities in the Visualization of Vasa Vasorum and Atherosclerotic Plaques

    Directory of Open Access Journals (Sweden)

    Zhonghua Sun

    2014-01-01

    Full Text Available Invasive angiography has been widely accepted as the gold standard to diagnose cardiovascular pathologies. Despite its superior resolution of demonstrating atherosclerotic plaque in terms of degree of lumen stenosis, the morphological assessment for the plaque is insufficient for the analysis of plaque components, and therefore, unable to predict the risk status or vulnerability of atherosclerotic plaque. There is an increased body of evidence to show that the vasa vasorum play an important role in the initiation, progression, and complications of atherosclerotic plaque leading to major adverse cardiac events. This paper provides an overview of the evidence-based reviews of various imaging modalities with regard to their potential value for comprehensive characterization of the composition, burden, and neovascularization of atherosclerotic plaque.

  2. Atherosclerosis and atheroma plaque rupture: imaging modalities in the visualization of vasa vasorum and atherosclerotic plaques.

    Science.gov (United States)

    Sun, Zhonghua

    2014-01-01

    Invasive angiography has been widely accepted as the gold standard to diagnose cardiovascular pathologies. Despite its superior resolution of demonstrating atherosclerotic plaque in terms of degree of lumen stenosis, the morphological assessment for the plaque is insufficient for the analysis of plaque components, and therefore, unable to predict the risk status or vulnerability of atherosclerotic plaque. There is an increased body of evidence to show that the vasa vasorum play an important role in the initiation, progression, and complications of atherosclerotic plaque leading to major adverse cardiac events. This paper provides an overview of the evidence-based reviews of various imaging modalities with regard to their potential value for comprehensive characterization of the composition, burden, and neovascularization of atherosclerotic plaque. PMID:24688380

  3. Multimodality imaging of carotid atherosclerotic plaque: Going beyond stenosis

    Science.gov (United States)

    Hingwala, Divyata; Kesavadas, Chandrasekharan; Sylaja, Padmavathy N; Thomas, Bejoy; Kapilamoorthy, Tirur Raman

    2013-01-01

    Apart from the degree of stenosis, the morphology of carotid atherosclerotic plaques and presence of neovascularization are important factors that may help to evaluate the risk and ‘vulnerability’ of plaques and may also influence the choice of treatment. In this article, we aim to describe the techniques and imaging findings on CTA, high resolution MRI and contrast enhanced ultrasound in the evaluation of carotid atherosclerotic plaques. We also discuss a few representative cases from our institute with the related clinical implications. PMID:23986615

  4. Multimodality imaging of carotid atherosclerotic plaque: Going beyond stenosis

    Directory of Open Access Journals (Sweden)

    Divyata Hingwala

    2013-01-01

    Full Text Available Apart from the degree of stenosis, the morphology of carotid atherosclerotic plaques and presence of neovascularization are important factors that may help to evaluate the risk and ′vulnerability′ of plaques and may also influence the choice of treatment. In this article, we aim to describe the techniques and imaging findings on CTA, high resolution MRI and contrast enhanced ultrasound in the evaluation of carotid atherosclerotic plaques. We also discuss a few representative cases from our institute with the related clinical implications.

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

    Directory of Open Access Journals (Sweden)

    Helene Hartwig

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

  6. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    International Nuclear Information System (INIS)

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

  7. Inhibiting extracellular matrix metalloproteinase inducer maybe beneficial for diminishing the atherosclerotic plaque instability

    Directory of Open Access Journals (Sweden)

    Xie S

    2009-01-01

    Full Text Available Atherosclerotic plaque rupture and local thrombosis activation in the artery cause acute serious incidents such as acute coronary syndrome and stroke. The exact mechanism of plaque rupture remains unclear but excessive degradation of the extracellular matrix scaffold by matrix-degrading metalloproteinases (MMPs has been implicated as one of the major molecular mechanisms in this process. Convincing evidence is available to prove that extracellular matrix metalloproteinase inducer (EMMPRIN induces MMP expression and is involved in the inflammatory responses in the artery wall. The inflammation and MMPs have been shown to play a critical role for atherosclerotic lesion development and progression. More recent data showed that increased EMMPRIN expression was associated with vulnerable atherosclerotic lesions. Therefore, we speculate that EMMPRIN may be pivotal for atherosclerotic plaque instability, and hence inhibition of EMMPRIN expression could be a promising approach for the prevention or treatment of atheroma instability.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2005-08-01

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

  12. Adiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques

    Directory of Open Access Journals (Sweden)

    Almer G

    2011-06-01

    Full Text Available Gunter Almer1,6, Karin Wernig2, Matthias Saba-Lepek3, Samih Haj-Yahya1, Johannes Rattenberger4, Julian Wagner4, Kerstin Gradauer3, Daniela Frascione3, Georg Pabst3, Gerd Leitinger5, Harald Mangge1, Andreas Zimmer2, Ruth Prassl31Clinical Institute of Medical and Chemical Laboratory Diagnostics, 2Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 3Institute of Biophysics and Nanosystems Research, Austrian Academy of Science, 4Institute for Electron Microscopy and Fine Structure Research, Graz University of Technology, 5Institute of Cell Biology, Histology and Embryology, Medical University of Graz, 6Center for Medical Research, Medical University of Graz, AustriaBackground: Atherosclerosis is a leading cause of mortality in the Western world, and plaque diagnosis is still a challenge in cardiovascular medicine. The main focus of this study was to make atherosclerotic plaques visible using targeted nanoparticles for improved imaging. Today various biomarkers are known to be involved in the pathophysiologic scenario of atherosclerotic plaques. One promising new candidate is the globular domain of the adipocytokine adiponectin (gAd, which was used as a targeting sequence in this study.Methods: gAd was coupled to two different types of nanoparticles, namely protamine-oligonucleotide nanoparticles, known as proticles, and sterically stabilized liposomes. Both gAd-targeted nanoparticles were investigated for their potency to characterize critical scenarios within early and advanced atherosclerotic plaque lesions using an atherosclerotic mouse model. Aortic tissue from wild type and apolipoprotein E-deficient mice, both fed a high-fat diet, were stained with either fluorescent-labeled gAd or gAd-coupled nanoparticles. Ex vivo imaging was performed using confocal laser scanning microscopy.Results: gAd-targeted sterically stabilized liposomes generated a strong signal by accumulating at the surface of

  13. 16S rRNA-based detection of oral pathogens in coronary atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Mahendra Jaideep

    2010-01-01

    Full Text Available Background: Atherosclerosis develops as a response of the vessel wall to injury. Chronic bacterial infections have been associated with an increased risk for atherosclerosis and coronary artery disease. The ability of oral pathogens to colonize in coronary atheromatous plaque is well known. Aim: The aim of this study was to detect the presence of Treponema denticola, Porphyromonas gingivalis and Campylobacter rectus in the subgingival and atherosclerotic plaques of patients with coronary artery disease. Materials and Methods: Fifty-one patients in the age group of 40-80 years with coronary artery disease were selected for the study. DNA was extracted from the plaque samples. The specific primers for T. denticola, C. rectus and P. gingivalis were used to amplify a part of the 16S rRNA gene by polymerase chain reaction. Statistical Analysis Used: Chi-square analysis, correlation coefficient and prevalence percentage of the microorganisms were carried out for the analysis. Results: Of the 51 patients, T. denticola, C. rectus and P. gingivalis were detected in 49.01%, 21.51% and 45.10% of the atherosclerotic plaque samples. Conclusions: Our study revealed the presence of bacterial DNA of the oral pathogenic microorganisms in coronary atherosclerotic plaques. The presence of the bacterial DNA in the coronary atherosclerotic plaques in significant proportion may suggest the possible relationship between periodontal bacterial infection and genesis of coronary atherosclerosis.

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  16. Quantitative evaluation of lipid concentration in atherosclerotic plaque phantom by near-infrared multispectral angioscope at wavelengths around 1200 nm

    Science.gov (United States)

    Matsui, Daichi; Ishii, Katsunori; Awazu, Kunio

    2015-07-01

    Atherosclerosis is a primary cause of critical ischemic diseases like heart infarction or stroke. A method that can provide detailed information about the stability of atherosclerotic plaques is required. We focused on spectroscopic techniques that could evaluate the chemical composition of lipid in plaques. A novel angioscope using multispectral imaging at wavelengths around 1200 nm for quantitative evaluation of atherosclerotic plaques was developed. The angioscope consists of a halogen lamp, an indium gallium arsenide (InGaAs) camera, 3 optical band pass filters transmitting wavelengths of 1150, 1200, and 1300 nm, an image fiber having 0.7 mm outer diameter, and an irradiation fiber which consists of 7 multimode fibers. Atherosclerotic plaque phantoms with 100, 60, 20 vol.% of lipid were prepared and measured by the multispectral angioscope. The acquired datasets were processed by spectral angle mapper (SAM) method. As a result, simulated plaque areas in atherosclerotic plaque phantoms that could not be detected by an angioscopic visible image could be clearly enhanced. In addition, quantitative evaluation of atherosclerotic plaque phantoms based on the lipid volume fractions was performed up to 20 vol.%. These results show the potential of a multispectral angioscope at wavelengths around 1200 nm for quantitative evaluation of the stability of atherosclerotic plaques.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Ida Rune

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

  19. In-vivo Attenuation and Equivalent Scatterer size parameters for Atherosclerotic Carotid Plaque: Preliminary Results

    OpenAIRE

    Shi, Hairong; Varghese, Tomy; Mitchell, Carol C; McCormick, Matthew; Dempsey, Robert J; Kliewer, Mark A.

    2009-01-01

    We have previously reported on the equivalent scatterer size, attenuation coefficient, and axial strain properties of atherosclerotic plaque ex-vivo. Since plaque structure and composition may be damaged during a carotid endarterectomy procedure, characterization of in-vivo properties of atherosclerotic plaque is essential. The relatively shallow depth of the carotid artery and plaque enables non-invasive evaluation of carotid plaque utilizing high frequency linear array transducers. We inves...

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

    Science.gov (United States)

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

    2000-05-01

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

  1. Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques

    Science.gov (United States)

    Cui, Dongyao; Yu, Xiaojun; Chen, Si; Liu, Xinyu; Tang, Hongying; Wang, Xianghong; Liu, Linbo

    2016-01-01

    Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals. PMID:27149381

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  3. Phage display identification of CD100 in human atherosclerotic plaque macrophages and foam cells.

    Directory of Open Access Journals (Sweden)

    Maria Carolina Aquino Luque

    Full Text Available Atherosclerosis is a complex disease in which vessels develop plaques comprising dysfunctional endothelium, monocyte derived lipid laden foam cells and activated lymphocytes. Considering that humans and animal models of the disease develop quite distinct plaques, we used human plaques to search for proteins that could be used as markers of human atheromas. Phage display peptide libraries were probed to fresh human carotid plaques, and a bound phage homologous to plexin B1, a high affinity receptor for CD100, was identified. CD100 is a member of the semaphorin family expressed by most hematopoietic cells and particularly by activated T cells. CD100 expression was analyzed in human plaques and normal samples. CD100 mRNA and protein were analyzed in cultured monocytes, macrophages and foam cells. The effects of CD100 in oxLDL-induced foam cell formation and in CD36 mRNA abundance were evaluated. Human atherosclerotic plaques showed strong labeling of CD100/SEMA4D. CD100 expression was further demonstrated in peripheral blood monocytes and in in vitro differentiated macrophages and foam cells, with diminished CD100 transcript along the differentiation of these cells. Incubation of macrophages with CD100 led to a reduction in oxLDL-induced foam cell formation probably through a decrease of CD36 expression, suggesting for the first time an atheroprotective role for CD100 in the human disease. Given its differential expression in the numerous foam cells and macrophages of the plaques and its capacity to decrease oxLDL engulfment by macrophages we propose that CD100 may have a role in atherosclerotic plaque development, and may possibly be employed in targeted treatments of these atheromas.

  4. Mechanical modeling of cholesterol crystallization in atherosclerotic plaques base on Micro-OCT images (Conference Presentation)

    Science.gov (United States)

    Luo, Yuemei; Liu, Xinyu; Chen, Si; Cui, Dongyao; Wang, Xianghong; Liu, Linbo

    2016-02-01

    Plaque rupture is the critical cause of cardiovascular thrombosis but this process is still under discussion. Recent studies show that, during crystallization, cholesterol crystals in atheromatous plaques accumulate rapidly in a limited space and may result in plaque rupture. However, the actual role of cholesterol crystals on plaque rupture remains unclear due to the lack of detailed morphological information of cholesterol crystals. In this study, we used a Micro-optical coherence tomography (µOCT) setup with 1-2 µm spatial resolution to extract the geometry of cholesterol crystals from human atherosclerotic artery ex vivo firstly. With measured dimensions of cholesterol crystals by this µOCT system (the average length and thickness of 269.1±80.16 µm and 3.0±0.33 µm), we developed a two-dimensional mechanical model in which rectangular shaped cholesterol crystals distribute at different locations spatially. We predicted the stress on the thin cap induced by the expansion of cholesterol crystals by use of finite-element method. Since a large portion of plaques (58%) rupture at points of peak circumferential stress (PCS), we used PCS as the primary indicator of plaque stability with blood pressure of 14.6 kPa on the lumen. The results demonstrate that loading of the concentrated crystals especially at the cap shoulder destabilize the plaque by proportionally increasing the PCS, while evenly distributed crystals loading along the cap might impose less PCS to the plaque than the concentrated case.

  5. Monocytes/macrophages activation contributes to b-gamma-glutamyltransferase accumulation inside atherosclerotic plaques

    OpenAIRE

    Belcastro, Eugenia; Franzini, Maria; Cianchetti, Silvana; Lorenzini, Evelina; Masotti, Silvia; Fierabracci, Vanna; Pucci, Angela; Pompella, Alfonso; Corti, Alessandro

    2015-01-01

    Background Gamma-glutamyltransferase (GGT) is a well-established independent risk factor for cardiovascular mortality related to atherosclerotic disease. Four GGT fractions have been identified in plasma, but only b-GGT fraction accumulates in atherosclerotic plaques, and correlates with other histological markers of vulnerability. The present study was aimed to evaluate whether macrophagic lineage cells may provide a source of b-GGT within the atherosclerotic plaque. Methods GGT expression a...

  6. Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice

    DEFF Research Database (Denmark)

    Bentzon, Jacob F; Sondergaard, Claus S; Kassem, Mustafa;

    2007-01-01

    circulating bone marrow-derived progenitor cells. Here, we analyzed the contribution of this mechanism to plaque healing after spontaneous and mechanical plaque disruption in apolipoprotein E knockout (apoE-/-) mice. METHODS AND RESULTS: To determine the origin of SMCs after spontaneous plaque disruption......GFP+ SMCs were detected. To examine the origin of healing SMCs in a model that recapitulates more features of human plaque rupture and healing, we developed a mechanical technique that produced consistent plaque disruption, superimposed thrombosis, and SMC-mediated plaque healing in apoE-/- mice. Mechanical...... originating from outside the local arterial segment were detected in healed plaques. CONCLUSIONS: Healing SMCs after atherosclerotic plaque disruption are derived entirely from the local arterial wall and not circulating progenitor cells in apoE-/- mice. Udgivelsesdato: 2007-Oct-30...

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

    OpenAIRE

    Engelen, Arna; Niessen, Wiro; Klein, Stefan; Groen, Harald; Verhagen, Hence; Wentzel, Jolanda; van der Lugt, Aad; de Bruijne, Marleen

    2014-01-01

    textabstractAtherosclerotic plaque composition can indicate plaque vulnerability. We segment atherosclerotic plaque components from the carotid artery on a combination of in vivo MRI and CT-angiography (CTA) data using supervised voxelwise classification. In contrast to previous studies the ground truth for training is directly obtained from 3D registration with histology for fibrous and lipid-rich necrotic tissue, and with μCT for calcification. This registration does, however, not provide a...

  8. Atherosclerotic Plaque Component Segmentation in Combined Carotid MRI and CTA Data Incorporating Class Label Uncertainty

    OpenAIRE

    van Engelen, A.; Niessen, W.J.; Klein, S.; Groen, H. C.; Verhagen, H. J. M.; Wentzel, J.J.; van der Lugt, A.; De Bruijne, M.

    2014-01-01

    Atherosclerotic plaque composition can indicate plaque vulnerability. We segment atherosclerotic plaque components from the carotid artery on a combination of in vivo MRI and CT-angiography (CTA) data using supervised voxelwise classification. In contrast to previous studies the ground truth for training is directly obtained from 3D registration with histology for fibrous and lipid-rich necrotic tissue, and with CT for calcification. This registration does, however, not provide accurate voxel...

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

    OpenAIRE

    2014-01-01

    Atherosclerotic plaque composition can indicate plaque vulnerability. We segment atherosclerotic plaque components from the carotid artery on a combination of in vivo MRI and CT-angiography (CTA) data using supervised voxelwise classification. In contrast to previous studies the ground truth for training is directly obtained from 3D registration with histology for fibrous and lipid-rich necrotic tissue, and with [Formula: see text]CT for calcification. This registration does, however, not pro...

  10. Data Mining of Atherosclerotic Plaque Transcriptomes Predicts STAT1-Dependent Inflammatory Signal Integration in Vascular Disease

    Directory of Open Access Journals (Sweden)

    Krzysztof Sikorski

    2014-08-01

    Full Text Available Atherosclerotic plaque development involves multiple extra- and intra-cellular signals engaging cells from the immune system and from the vasculature. Pro-inflammatory pathways activated by interferon gamma (IFNγ and toll-like receptor 4 (TLR4 ligands are profoundly involved in plaque formation and have been shown to involve cross-talk in all atheroma-interacting cell types leading to increased activation of signal transducer and activator of transcription-1 (STAT1 and elevated expression of pro-inflammatory mediators. Here we demonstrate that in Gene Expression Omnibus repository (GEO deposited microarray datasets, obtained from human coronary and carotid atherosclerotic plaques, a significant increase in expression of pro-inflammatory and immunomodulatory genes can be detected. Moreover, increased expression of multiple chemokines, adhesion molecules and matrix-remodeling molecules was commonly detected in both plaque types and correlated with the presence of putative STAT1 binding sites in their promoters, suggesting strong involvement of STAT1 in plaque development. We also provide evidence to suggest that STAT1-nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB or STAT1-interferon-regulated factor (IRF regulatory modules are over-represented in the promoters of these inflammatory genes, which points to a possible contribution of IFNγ and TLR4 cross-talk in the process of atherogenesis. Finally, a subset of these genes encodes for secreted proteins that could serve as a basis of a non-invasive diagnostic assay. The results of our in silico analysis in vitro provide potential evidence that STAT1-dependent IFNγ-TLR4 cross-talk plays a crucial role in coronary and carotid artery plaque development and identifies a STAT1-dependent gene signature that could represent a novel diagnostic tool to monitor and diagnose plaque progression in human atherosclerosis.

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

    Directory of Open Access Journals (Sweden)

    Leon J Schurgers

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-15

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

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

    International Nuclear Information System (INIS)

    Evaluate the progression of coronary atherosclerotic plaque during follow-up, and its association with cardiovascular risk factors. Fifty-six atherosclerotic patients with plaque were enrolled in this retrospective study. Patient's plaque was detected on repeat 64-slice multidetector CT scans with a mean interval of 25 ± 10 months changes in calcified and non-calcified plaque volumes and cardiovascular risk factors were assessed over time. Absolute and relative changes in plaque volume were compared, and the association between rapid progression and cardiovascular risk factors was determined. Diameter of the stenosis, length, calcified and non-calcified lesion plaque volumes increased significantly on follow-up CT. Absolute and relative annual changes in plaque volumes were significantly greater in non-calcified plaque (median, 22.7 mm3, 90.4%) than in calcified plaque (median, 0.7 mm3, 0%). Obesity, smoking, hypertension, hypercholesterolemia, and low high-density lipoprotein were significant predictors of progression of non-calcified plaque. Progression of calcified plaque was not associated with any cardiovascular risk factors. Coronary plaque volume increased significantly on follow-up CT. The rate of progression is related to non-calcified plaque than to calcified plaque. Cardiovascular risk factors are independently associated with the rapid progression of non-calcified plaque volume, but not associated with the progression of calcified plaque.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Huilin [Department of Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Zhao, Xihai [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing 100084 (China); Liu, Xiaosheng; Cao, Ye [Department of Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Hippe, Daniel S.; Sun, Jie [Department of Radiology, University of Washington, Seattle, WA 98109 (United States); Li, Feiyu [Department of Radiology, Peking University First Hospital, Beijing 100034 (China); Xu, Jianrong, E-mail: renjixjr@yahoo.com.cn [Department of Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Yuan, Chun [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing 100084 (China); Department of Radiology, University of Washington, Seattle, WA 98109 (United States)

    2013-09-15

    Background and purpose: It remains unclear whether direct vessel wall imaging can identify carotid high-risk lesions in symptomatic subjects and whether carotid plaque characteristics are more effective indicators for cerebral infarct severity than stenosis. This study sought to determine the associations of carotid plaque characteristics by MR imaging with stenosis and acute cerebral infarct (ACI) sizes on diffusion weighted imaging (DWI). Materials and methods: One hundred and fourteen symptomatic patients underwent carotid and brain MRI. ACI volume was determined from symptomatic internal carotid artery territory on DWI images. Ipsilateral carotid plaque morphological and compositional characteristics, and stenosis were also determined. The relationships between carotid plaque characteristics, stenosis and ACIs size were then evaluated. Results: In carotid arteries with 30–49% stenosis, 86.7% and 26.7% were found to have lipid-rich necrotic core (LRNC) and intraplaque hemorrhage, respectively. Furthermore, 45.8% of carotid arteries with 0–29% stenosis developed LRNCs. Carotid morphological measurements, such as % wall volume, and the LRNC size were significantly associated with ipsilateral ACIs volume before and after adjustment for significant demographic factors (age and LDL) or stenosis in patients with carotid plaque (all p < 0.05). Conclusions: A substantial number of high-risk plaques characterized by vessel wall imaging exist in carotid arteries with lower grade stenosis. In addition, carotid plaque characteristics, particularly the % wall volume and LRNC size, are independently associated with cerebral infarction as measured by DWI lesions. Our findings indicate that characterizing atherosclerotic plaque by MR vessel wall imaging might be useful for stratification of plaque risk and infarction severity.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  16. Alternation of histone and DNA methylation in human atherosclerotic carotid plaques.

    Science.gov (United States)

    Greißel, A; Culmes, M; Napieralski, R; Wagner, E; Gebhard, H; Schmitt, M; Zimmermann, A; Eckstein, H-H; Zernecke, A; Pelisek, J

    2015-08-01

    Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development. PMID:25993995

  17. Resolution of apoptosis in atherosclerotic plaque by dietary modification and statin therapy

    OpenAIRE

    Hartung, D; Sarai, M; Petrov, A.; Kolodgie, F; Narula, N.; Verjans, J.; Virmani, R; Reutelingsperger, C; Hofstra, L; Narula, J

    2005-01-01

    Although apoptosis within atherosclerotic plaques is associated with plaque vulnerability and rupture, the role of inhibition of the apoptotic process is not clear. We evaluated the impact of dietary modification and statin therapy (measures known to favorably influence outcomes in coronary disease) on the incidence of apoptosis in experimental atherosclerotic lesions. Methods: A total of 30 animals were studied; 1 group of 6 animals served as the controls (group 1), and the remaining 24 anim...

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

    Directory of Open Access Journals (Sweden)

    Kurt Reifenberg

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

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

    Science.gov (United States)

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

    2016-06-01

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

  20. PET Imaging of Atherosclerotic Disease: Advancing Plaque Assessment from Anatomy to Pathophysiology.

    Science.gov (United States)

    Evans, Nicholas R; Tarkin, Jason M; Chowdhury, Mohammed M; Warburton, Elizabeth A; Rudd, James H F

    2016-06-01

    Atherosclerosis is a leading cause of morbidity and mortality. It is now widely recognized that the disease is more than simply a flow-limiting process and that the atheromatous plaque represents a nidus for inflammation with a consequent risk of plaque rupture and atherothrombosis, leading to myocardial infarction or stroke. However, widely used conventional clinical imaging techniques remain anatomically focused, assessing only the degree of arterial stenosis caused by plaques. Positron emission tomography (PET) has allowed the metabolic processes within the plaque to be detected and quantified directly. The increasing armory of radiotracers has facilitated the imaging of distinct metabolic aspects of atherogenesis and plaque destabilization, including macrophage-mediated inflammatory change, hypoxia, and microcalcification. This imaging modality has not only furthered our understanding of the disease process in vivo with new insights into mechanisms but has also been utilized as a non-invasive endpoint measure in the development of novel treatments for atherosclerotic disease. This review provides grounding in the principles of PET imaging of atherosclerosis, the radioligands in use and in development, its research and clinical applications, and future developments for the field. PMID:27108163

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  2. Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice.

    Science.gov (United States)

    Jia, Fang; Wu, Chunfang; Chen, Zhenyue; Lu, Guoping; Sun, Jianhui

    2016-04-01

    Endoplasmic reticulum (ER) stress has been suggested to play a role in the progression of plaque vulnerability and the occurrence of acute complications of coronary atherosclerosis. Atorvastatin is known to exert pleiotropic effects on the cardiovascular system. The present study aimed to examine the stabilizing effects of atorvastatin on vulnerable plaques within hyperhomocysteinemic apolipoprotein E‑deficient (ApoE‑/‑) mice, and to investigate the potential mechanisms underlying ER stress in ApoE‑/‑ mice and macrophages. In the present study, ApoE‑/‑ mice were administrated methionine or atorvastatin, and were sacrificed after 2 months. Necrotic core size, collagen content and inflammatory cytokine infiltration were subsequently measured in the aortic lesions, in order to investigate plaque stability. Treatment with atorvastatin decreased the number and size of necrotic cores, increased collagen content, and downregulated tumor necrosis factor (TNF)‑α and matrix metalloproteinase (MMP)‑9 mRNA expression, as compared with the methionine group. Immunohistochemical analysis indicated that atorvastatin administration prevented ER stress activation in aortic lesions of hyperhomocysteinemic mice. Furthermore, macrophages were challenged with homocysteine (Hcy) in the presence or absence of atorvastatin and thapsigargin (an ER stress inducer). Atorvastatin suppressed Hcy‑induced ER stress, and downregulated TNF‑α and MMP‑9 mRNA expression in the macrophages. Conversely, thapsigargin attenuated the inhibitory effects of atorvastatin against Hcy‑induced TNF‑α and MMP‑9 expression. These results indicated that hyperhomocysteinemia may promote atherosclerotic plaque development and instability. In addition, atorvastatin was able to improve atherosclerotic plaque stability in hyperhomocysteinemic mice by inhibiting ER stress. PMID:26956896

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    -lymphocytes). These interactions can be mediated by proteins secreted from these cells, which therefore exert an important role in the atherosclerotic process. We recently described a novel strategy for the characterization of the human atherosclerotic plaque secretome, combining two-dimensional gel electrophoresis...... are unknown. Thus, the role that phosphorylated HSP27 could play in the atherosclerotic process is actually under study. The present work shows the strategies employed to characterize the phosphorylation in the HSP27 secreted by atheroma plaque samples. The application of liquid chromatography tandem...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-19

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

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

    International Nuclear Information System (INIS)

    Highlights: ► Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. ► PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-κB activation. ► Piperlongumine reduced vascular smooth muscle cell activation through PDGF-Rβ and NF-κB-signaling. ► PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-κB) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase Cγ1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-κB—a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

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

    OpenAIRE

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

    2011-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    International Nuclear Information System (INIS)

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

  10. A framework for the co-registration of hemodynamic forces and atherosclerotic plaque components

    International Nuclear Information System (INIS)

    Local hemodynamic forces, such as wall shear stress (WSS), are thought to trigger cellular and molecular mechanisms that determine atherosclerotic plaque vulnerability to rupture. Magnetic resonance imaging has emerged as a powerful tool to characterize human carotid atherosclerotic plaque composition and morphology, and to identify plaque features shown to be key determinants of plaque vulnerability. Image-based computational fluid dynamics has allowed researchers to obtain time-resolved WSS information of atherosclerotic carotid arteries. A deeper understanding of the mechanisms of initiation and progression of atherosclerosis can be obtained through the comparison of WSS and plaque composition and morphology. To date, however, advance in knowledge has been limited greatly due to the lack of a reliable infrastructure to perform such analysis. The aim of this study is to establish a framework that will allow for the co-registration and analysis of the three-dimensional distribution of WSS and plaque components and morphology. The use of this framework will lead to future studies targeted to determining the role of WSS in atherosclerotic plaque progression and vulnerability. (paper)

  11. Nox4 NADPH oxidase contributes to smooth muscle cell phenotypes associated with unstable atherosclerotic plaques

    Directory of Open Access Journals (Sweden)

    Shaoping Xu

    2014-01-01

    Full Text Available Plaque instability associated with acute coronary syndromes results in part from apoptosis and senescence of cells within the atherosclerotic (AS lesion. Increased cellular oxidative stress has been proposed to contribute to plaque progression and changes in composition, leading to plaque instability. Our objective was to examine the role of NADPH oxidase in smooth muscle cell (SMC phenotypes associated with an unstable plaque. Aortae were isolated from pre-lesion (8 weeks of age and post-lesion (35 weeks of age hypercholesterolemic mice (ApoE−/−/LDLR−/−, AS, and age-matched normal C57BL/6J mice. We observed an age-dependent increase in reactive oxygen species (ROS in aorta from AS mice, with evidence for elevated ROS prior to lesion development. Whereas macrophage infiltration was restricted to the lesion, oxidized lipids extended beyond the plaque and into the vessel wall. Consistent with these findings, we observed dynamic changes in the expression of NADPH oxidases in AS vessels. Specifically, Nox1 expression was increased early and decreased with lesion progression, while induction of Nox4 was a late event. Nox2 and p22phox were elevated throughout lesion development. Similar to observations in aortae, SMCs isolated from the lesion of AS aortae had decreased Nox1 and increased Nox4 levels as compared to SMCs from normal mice. AS SMCs demonstrated increased generation of ROS, cell cycle arrest, evidence of senescence, and increased susceptibility to apoptosis. Overexpression of Nox4 in normal SMCs recapitulated the phenotypes of the AS SMCs. We conclude that increased expression of Nox4 in AS may drive SMC phenotypes that lead to the plaque instability and rupture responsible for myocardial infarction and stroke.

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

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhe Wang

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

  14. Cross-Polarization Optical Coherence Tomography in Evaluation of Atherosclerotic Plaque Structure

    Directory of Open Access Journals (Sweden)

    Gubarkova Е.V.

    2013-12-01

    Full Text Available The cross-polarization optical coherence tomography (CP OCT technique allows for tissue structure imaging by registration of backscattered radiation in initial and orthogonal polarizations and further comparison of the obtained images. Spatial structure of collagen fibers gives rise not only to backscattering of probing radiation, but also to evolution of its polarization state during propagation through the tissue (depolarization. Collagen fibers of the fibrous cap play a key role in determining the stability of atherosclerotic plaques. Inflammation observed in atherosclerosis is the principal mechanism of collagen fibers disorganization, therefore, the assessment of the depolarizing properties of the fibrous cap can characterize an atherosclerotic plaque as being “vulnerable” to rupture. The aim of the study was to evaluate CP OCT efficiency to determine the condition of collagen fibers of an atherosclerotic plaque fibrous cap, which characterize its “vulnerability”. Materials and Methods. 54 post mortem samples of intact human aorta and aorta with atherosclerotic plaques at different stages were studied. The study involved 150 CP OCT-images in which the value of OCT signal in orthogonal polarization was used to evaluate the ratio of organized and disorganized by inflammation collagen fibers within the fibrous cap. For histological imaging comparison we used hematoxylin-eosine and picrosirius red staining with evaluation in polarized light. Numerical analysis of CP OCT-images was used as a complementary tool for visual assessment. Results. We showed CP OCT to have significant advantages over the traditional OCT in the assessment of atherosclerotic plaque. In orthogonal CP OCT-image one can differentiate the main structural components of a plaque: a fibrous cap and a lipid core. The thickness of the fibrous cap in the orthogonal polarization image correlates with the thickness of the fibrous cap measured from histological preparations

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

    OpenAIRE

    Sezer ED; Sozmen EY; Nart D; Onat T

    2011-01-01

    Ebru Demirel Sezer1, Eser Yildirim Sozmen1, Deniz Nart2, Taner Onat11Medical Biochemistry, 2Pathology Department, Ege University School of Medicine, Izmir, TurkeyBackground: The aim of this study was to determine the oxidant–antioxidant status and lipid peroxidation products, as well as paraoxonase and atherosclerotic plaque formation, in a hypercholesterolemic atherosclerosis rabbit model to investigate the effects of atorvastatin in the atherosclerotic process.Methods: Forty male ...

  16. Platelet activation and platelet-monocyte aggregate formation by the atherosclerotic plaque lipid lysophosphatidic acid

    OpenAIRE

    Haserück, Nadine

    2007-01-01

    Oxidized LDL and platelets play a central role in the pathogenesis of atherosclerosis and ischemic cardiovascular diseases. Lysophosphatidic acid (LPA) is a thrombogenic substance that accumulates in mildly-oxidized LDL and in human atherosclerotic lesions, and is responsible for the initial platelet activation, shape change, induced by mildly-oxidized LDL and extracts of lipid-rich atherosclerotic plaques (Siess et al., 1999 Proc Natl Acad Sci USA 1999). LPA directly induced platelet shape c...

  17. Histopathologic Characteristics of Atherosclerotic Coronary Disease and Implications of the Findings for the Invasive and Noninvasive Detection of Vulnerable Plaques

    Science.gov (United States)

    Narula, Jagat; Nakano, Masataka; Virmani, Renu; Kolodgie, Frank D.; Petersen, Rita; Newcomb, Robert; Malik, Shaista; Fuster, Valentin; Finn, Aloke V.

    2014-01-01

    Objectives The goal of this study was to identify histomorphologic characteristics of atherosclerotic plaques and to determine the amenability of some of these components to be used as markers for invasive and noninvasive imaging. Background Rupture of the atherosclerotic plaques is responsible for the majority of acute coronary events, and the culprit lesions demonstrate distinct histopathologic features. It has been tacitly believed that plaque rupture (PR) is associated with angiographically minimally occlusive lesions. Methods We obtained 295 coronary atherosclerotic plaques, including stable (fibroatheroma [FA]; n = 105), vulnerable (thin-cap fibroatheroma [TCFA]; n = 88), and disrupted plaques (plaque rupture [PR]; n = 102) from the hearts of 181 men and 32 women who had died suddenly. The hierarchical importance of fibrous cap thickness, percent luminal stenosis, macrophage area, necrotic core area, and calcified plaque area was evaluated by using recursive partitioning analysis. Because clinical assessment of fibrous cap thickness is not possible by noninvasive imaging, it was excluded from the second set of partitioning analysis. Results Thickness of the fibrous cap emerged as the best discriminator of plaque type; the cap thickness measured 84-μm cap thickness. Although the majority of TCFA were found in the 54- to 84-μm thickness group, those with <54-μm thickness were more likely to show <74% luminal stenosis (area under the curve: FA, 1.0; TCFA, 0.89; PR, 0.90). After exclusion of cap thickness, analysis of the plaque characteristics revealed macrophage infiltration and necrotic core to be the 2 best discriminators of plaque types (area under the curve: FA, 0.82; TCFA, 0.58; PR, 0.72). More than 75% cross-section area stenosis was seen in 70% of PR and 40% of TCFA; only 5% PR and 10% TCFA were <50% narrowed. Conclusions This postmortem study defines histomorphologic characteristics of vulnerable plaques, which may help develop imaging strategies for

  18. Study of 99mTc-Ap4A in detection of experimental atherosclerotic plaques

    International Nuclear Information System (INIS)

    Aim: The observe was to study 99mTc labeling diadenosine tetraphosphate (Ap4A) which can bind on P2 purine receptors on atherosclerotic lesions for imaging experimental atherosclerotic plaques in New Zealand White (NZW) rabbits. Material and Methods: Studies were performed in 20 male NZW rabbits ranging in weight from 1.5-2.0 kg. Rabbits were intravenous administrated bovine serum albumin (250 mg/kg body weight), and then fed with cholesterol 1.0g, lard 3.0 g every day for 2 months. To couple the 99mTc to Ap4A, 1mg of Ap4A was dissolved in 1ml of saline and added to a solution of technetium pertechnetate (740-1 850 MBq/1 ml). One milliliter of stannous tartrate solution (25 mg in 25 ml of 0.01M HCl) was added to reduce the 99mTc, and the solution was mixed under a nitrogen atmosphere for 5-15 min. The mixture was then separate on a Sephadex G-25 column (2 cm long, 0.8 cm diameter). The product was eluted with saline into vials. The product was tested for radiochemistry purity on TLC plates developed with saline and acetone. 0.74 MBq 99mTc-Ap4A was injected to the tail veins of KM mice. The animals were sacrificed in 5 min, 30 min, 1 hr, 2 hr and 24 hr post injection. Samples of blood, heart, lung, liver, spleen, kidney, stomach, muscle and intestines were washed, their radioactivity were measured with a well type gamma counter. To correct for radioactive decay and permit calculation of the concentration of radioactivity in each organ as a fraction of the administered dose, aliquots of the injected doses (IDs) were counted simultaneously. The results were expressed as %ID/g. 30 minutes after intravenous injection of 74 MBq 99mTc-Ap4A, 5 normal NZW rabbits and 5 NZW rabbits with atherosclerotic lesions were sacrificed; their aortas were removed and covered with autoradiographic films (Kodak X-OMAT AR). Exposed for 24 hours in refrigerator, the films were developed and fixed, to get 99mTc-Ap4A autoradiograms. In another 5 NZW rabbits with atherosclerotic lesions

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

  1. Automatic plaque characterization and vessel wall segmentation in magnetic resonance images of atherosclerotic carotid arteries

    Science.gov (United States)

    Adame, Isabel M.; van der Geest, Rob J.; Wasserman, Bruce A.; Mohamed, Mona; Reiber, Johan H. C.; Lelieveldt, Boudewijn P. F.

    2004-05-01

    Composition and structure of atherosclerotic plaque is a primary focus of cardiovascular research. In vivo MRI provides a meanse to non-invasively image and assess the morphological features of athersclerotic and normal human carotid arteries. To quantitatively assess the vulnerability and the type of plaque, the contours of the lumen, outer boundary of the vessel wall and plaque components, need to be traced. To achieve this goal, we have developed an automated contou detection technique, which consists of three consecutive steps: firstly, the outer boundary of the vessel wall is detected by means of an ellipse-fitting procedure in order to obtain smoothed shapes; secondly, the lumen is segnented using fuzzy clustering. Thre region to be classified is that within the outer vessel wall boundary obtained from the previous step; finally, for plaque detection we follow the same approach as for lumen segmentation: fuzzy clustering. However, plaque is more difficult to segment, as the pixel gray value can differ considerably from one region to another, even when it corresponds to the same type of tissue. That makes further processing necessary. All these three steps might be carried out combining information from different sequences (PD-, T2-, T1-weighted images, pre- and post-contrast), to improve the contour detection. The algorithm has been validated in vivo on 58 high-resolution PD and T1 weighted MR images (19 patients). The results demonstrate excellent correspondence between automatic and manual area measurements: lumen (r=0.94), outer (r=0.92), and acceptable for fibrous cap thickness (r=0.76).

  2. Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

    DEFF Research Database (Denmark)

    Barascuk, Natasha; Skjøt-Arkil, Helene; Register, Thomas C; Larsen, Lise; Byrjalsen, Inger; Christiansen, Claus; Karsdal, Morten A

    2010-01-01

    BACKGROUND: Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular...... matrix (ECM) of atherosclerotic plaques by cathepsin K mediated processes. METHODS: We 1) cultured human macrophages on ECM and measured cathepsin K generated fragments of type I collagen (C-terminal fragments of Type I collagen (CTX-I) 2) investigated the presence of CTX-I in human coronary arteries and......-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in...

  3. The content of copper and zinc in human ulcered atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Radak Đorđe

    2004-01-01

    Full Text Available INTRODUCTION Copper and zinc have significant antiatherogenic effect influencing activity of antioxidant enzyms (giutathion-peroxidase i superoxid-dismutase, mechanism of apoptosis and other mechanisms. Few studies showed increased copper and zinc concentration in atherosclerotic plaque in comparison to normal vascular tissue. AIM The aim of the study was to compare copper and zinc concentrations in carotid artery tissue without significant atherosclerotic changes and human ulcered atherosclerotic plaque. MATERIAL AND METHODS Study was conducted on 66 patients. Carotid endarterectomy due to the significant carotid atherosclerotic changes with cerebrovascular disorders was performed in 54 patients (81.8%. Control group consisted of 12 patients (18.2% without carotid atherosclerotic changes operated due to the symptomatic kinking and coiling of carotid artery. Operated group consisted of 38 man (62.96% and 16 woman (37.04%. Control group had the same number of patients: six men (50% and six women (50%. Preoperatively, all patients were examined by vascular surgeon, neurologist and cardiologist. Duplex sonografy of carotid and vertebral arteries was performed by Aloca DSD 630 ultrasound with mechanical and linear transducer 7.7 MHz. Indication for surgical treatment was obtained according to non-invasive diagnostic protocol and neurological symptoms. Copper and zinc concentration in human ulcered atherosclerotic plaque and carotid artery segment were estimated by spectophotometry (Varian AA-5. RESULTS Average age of our patients was 59.8±8.1 years. For males average age was 76.1 ±9.8 years. And for females 42.4±5.8 years. In group with carotid endarterectomy female patients were significantly younger than male patients (p<0.01. In group with carotid endarterectomy clinically determined neurological disorders were found in 47 patients (87.03%-35 male (74.47% and 12 female patients (25.53%. Regarding risk factors for cardiovascular diseases, no

  4. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    International Nuclear Information System (INIS)

    Increased expression of αvβ3/αvβ5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel 68Ga-DOTA-RGD peptide binds with high affinity to αvβ3/αvβ5 integrin. The aim of this study was to investigate the uptake of the 68Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered 68Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR-/-ApoB100/100 atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced 68Ga. The tracer had reasonably good specific radioactivity (8.7 ± 1.1 GBq/μmol) and was quite stable in vivo. According to ex vivo biodistribution results, 68Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of 68Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio ± SD 1.4 ± 0.1, p = 0.0004). We observed that 68Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

  5. Assessment of 320-slice computed tomography angiography in distinguishing hemorrhage in carotid atherosclerotic plaques

    Directory of Open Access Journals (Sweden)

    Xiao-jie ZHANG

    2014-01-01

    Full Text Available Objective To assess the value of 320⁃slice computed tomography angiography (CTA in distinguishing hemorrhage/thrombus from lipid-rich necrotic core (LRNC in atherosclerotic plaques of carotid artery. Methods Thirty-seven subjects who prepared to perform carotid endarterectomy (CEA, with stenosis rate about 50%-99% in at least unilateral carotid artery detected by ultrasound, were enrolled in this study. Both 320-slice CTA and 3.0T high-resolution MRI were conducted within one week before operation. CTA, MRI and pathological sections were matched with the carotid bifurcation and calcification features as the mark. According to American Heart Association (AHA modified classification, CT slices were selected and divided into 2 groups: Type Ⅳ -Ⅴ (lipid plaques and Type Ⅵ (hemorrhage plaques, and the density difference between lipid plaques and hemorrhage/thrombus plaques was analyzed. Results A total of 217 slices were included in final analysis, including 88 slices of Type Ⅳ -Ⅴ (lipid plaques and 129 slices of Type Ⅵ (hemorrhage plaques. There was statistically significant difference in CT value between 2 groups. The mean CT value of lipid necrosis core in Type Ⅳ -Ⅴ and hemorrhage/thrombus in Type Ⅵ was (28.07 ± 26.84 and (97.17 ± 35.82 HU respectively, and the former was significantly lower than the latter (t = 16.141, P = 0.000. Conclusions CTA can distinguish hemorrhage/thrombus from lipid-rich necrotic core in carotid atherosclerotic plaques.

  6. Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase

    DEFF Research Database (Denmark)

    Morgan, P E; Laura, R P; Maki, R A;

    2015-01-01

    appreciably altered. Serum MPO levels steadily increased in mice on the high-fat diet, however, comparison of SCN(-)-supplemented versus control mice showed no significant changes in MPO protein, cholesterol, or triglyceride levels; thiol levels were decreased in supplemented mice at one time-point. Plaque...... curve (AUC). Mean serum SCN(-) concentrations were elevated in the supplemented mice (200-320 μM) relative to controls (< 120 μM). Normalized aortic root plaque areas at sacrifice were 26% lower in the SCN(-)-supplemented mice compared with controls (P = 0.0417), but plaque morphology was not...

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Omid MASOUMI

    2015-10-01

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

  9. Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Bo Li

    Full Text Available Although there is evidence that visfatin is associated with atherogenesis, the effect of visfatin on plaque stability has not yet been explored.In vivo, vulnerable plaques were established by carotid collar placement in apolipoprotein E-deficient (ApoE-/- mice, and lentivirus expressing visfatin (lenti-visfatin was locally infused in the carotid artery. The lipid, macrophage, smooth muscle cell (SMC and collagen levels were evaluated, and the vulnerability index was calculated. In vitro, RAW264.7 cells were stimulated with visfatin, and the MMPs expressions were assessed by western blot and immunofluorescence. And the mechanism that involved in visfatin-induced MMP-8 production was investigated.Transfection with lenti-visfatin significantly promoted the expression of visfatin which mainly expressed in macrophages in the plaque. Lenti-visfatin transfection significantly promoted the accumulation of lipids and macrophages, modulated the phenotypes of smooth muscle cells and decreased the collagen levels in the plaques, which significantly decreased the plaque stability. Simultaneously, transfection with lenti-visfatin significantly up-regulated the expression of MMP-8 in vivo, as well as MMP-1, MMP-2 and MMP-9. Recombinant visfatin dose- and time-dependently up-regulated the in vitro expression of MMP-8 in macrophages. Visfatin promoted the translocation of NF-κB, and inhibition of NF-κB significantly reduced visfatin-induced MMP-8 production.Visfatin increased MMP-8 expression, promoted collagen degradation and increased the plaques vulnerability index.

  10. Characteristics of carotid atherosclerotic plaques of chronic lipid apheresis patients as assessed by In Vivo High-Resolution CMR - a comparative analysis

    Directory of Open Access Journals (Sweden)

    Grimm Jochen M

    2012-11-01

    Full Text Available Abstract Background Components of carotid atherosclerotic plaques can reliably be identified and quantified using high resolution in vivo 3-Tesla CMR. It is suspected that lipid apheresis therapy in addition to lowering serum lipid levels also has an influence on development and progression of atherosclerotic plaques. The purpose of this study was to evaluate the influence of chronic lipid apheresis (LA on the composition of atherosclerotic carotid plaques. Methods 32 arteries of 16 patients during chronic LA-therapy with carotid plaques and stenosis of 1–80% were matched according to degree of stenosis with 32 patients, who had recently suffered an ischemic stroke. Of these patients only the asymptomatic carotid artery was analyzed. All patients underwent black-blood 3 T CMR of the carotids using parallel imaging and dedicated surface coils. Cardiovascular risk factors were recorded. Morphology and composition of carotid plaques were evaluated. For statistical evaluation Fisher’s Exact and unpaired t-test were used. A p-value Results Patients in the LA-group were younger (63.5 vs. 73.9. years, p2, p Conclusion Results of this study suggest that, despite a severer risk profile for cardiovascular complications in LA-patients, chronic LA is associated with significantly lower lipid content in carotid plaques compared to plaques of patients without LA with similar degrees of stenosis, which is characteristic of clinically stable plaques.

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

    Science.gov (United States)

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

    2014-01-01

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

  12. A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation

    Science.gov (United States)

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

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show this effect is mediated through inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show they accumulate in atherosclerotic lesions where they directly affect plaque macrophages. Finally we demonstrate that a three-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a one-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation. PMID:24445279

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

    Science.gov (United States)

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

    1987-10-01

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

  14. The effect of serum MMP-9 and IL-6 on the vulnerability of carotid atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    WANG Wei

    2012-04-01

    Full Text Available Objective To explore the relationship of MMP-9 and IL-6 and the vulnerability of carotid atherosclerotic plaque. Methods According to the plaque vulnerability, 69 patients with acute cerebral infarction were divided into vulnerable plaque group (n = 35 and unvulnerable plaque group (n = 34. Twenty healthy subjects were selected as controls (control group. The levels of serum IL-6 and MMP-9 were examined. Results The level of MMP-9 and IL-6 in the unvulnerable plaque group was significantly higher than that in control group (P = 0.000, for all. The level of MMP-9 and IL-6 in the vulnerable plaque group was higher than that in the unvulnerable plaque group and control group (P = 0.000, for all. A positive correlation was observed between the expression of MMP-9 and IL-6 plaque (r = 0.836, P = 0.043. Conclusion MMP-9 and IL-6 are important factors for the promotion of vulnerable plaque. IL-6 may up-regulate the expression of MMP-9.

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

    International Nuclear Information System (INIS)

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

  16. Vulnerability of atherosclerotic plaques is associated with type I interferon in a murine model of lupus and atherosclerosis.

    Science.gov (United States)

    Zhang, C Y; Qu, B; Ye, P; Li, J; Bao, C D

    2015-01-01

    This study aimed to investigate the relationship between type I interferon (IFN-I) and plaque stability in pristane-treated apolipoprotein E-knockout (ApoE(-/-)) mice. Antinuclear antibody (ANA) and extractable nuclear antigen antibody (ENA) levels were measured by immunofluorescence and enzyme-linked immunospot assay. Atherosclerotic plaques were detected by Sirius red/fast green staining. Cell apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling. Gene expression was determined by real-time PCR analyses. We found that pristane-treated ApoE(-/-) mice developed a lupus-like syndrome characterized by an increased production of serum ANA and ENA. Pristane treatment decreased the collagen content and increased the number of apoptotic cells in plaques. Moreover, IFN-induced ISG15, IFIT1-1, and IFIT1-2 gene expression was increased in peripheral blood cells and aortic plaques. An IFN-α-stimulated macrophage supernatant inhibited collagen type I, alpha 1 gene expression in vascular smooth muscle cells. We concluded that the vulnerability of plaques was associated with the activation of IFN-I in pristane-treated ApoE(-/-) mice. Thus, we speculated that the higher prevalence of cardiovascular events in patients with systemic lupus erythematosus could be due to plaque instability. PMID:26600548

  17. Multislice CT characteristics of coronary atherosclerotic plaques in acute coronary syndrome

    International Nuclear Information System (INIS)

    Objective: To compare the plaque characteristics of acute coronary, syndrome (ACS) and stable angina (SA) by multislice CT(MSCT). Methods: MSCT images of 27 patients with ACS and SA were compared. Results: The frequency of positive vascular remodeling was significantly different in ACS (19/31) and SA (6/41, χ2=16.95, P2=8.00, P2=3.62, P<0.05). The mean CT value of non- calcified plaques in ACS [(35.0±15.1) HU] was lower than in SA [(67.5±26.5) HU(t=4.82,P< 0.01)]. Conclusion: The MSCT characteristics of atherosclerotic plaques in ACS include positive vascular remodeling, low plaque density, spotty calcification, and eccentric stenosis. (authors)

  18. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    Science.gov (United States)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2000-01-01

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

  1. Associations of Biomarkers of Atherosclerotic Plaques Instability (MMP-9, TIMP-1 and Zinc Levels in Carotid Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Gulnora A. Rozikhodjaeva

    2015-03-01

    Full Text Available The levels of matrix metalloproteinase-9 (MMP-9 and its tissue inhibitor (TIMP-1 in serum, and the concentration of Zn in the serum, hair and carotid atherosclerotic plaques were examined. The relationships zinc-dependent endopeptidases as biomarkers instability of atherosclerotic plaques and zinc in patients with carotid atherosclerosis were studied. The results contribute to the selection of patients at high risk for cardiovascular events.

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

    OpenAIRE

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

    2015-01-01

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

  3. Selective expansion of influenza A virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques

    OpenAIRE

    Keller, Tymen; Meer, Jelger; Teeling, Peter; Sluijs, Koenraad; Idu, Mirza; Rimmelzwaan, Guus; Levi, Michael; Wal, Allard; Boer, Onno

    2008-01-01

    textabstractBACKGROUND AND PURPOSE - Evidence is accumulating that infection with influenza A virus contributes to atherothrombotic disease. Vaccination against influenza decreases the risk of atherosclerotic syndromes, indicating that inflammatory mechanisms may be involved. We tested the hypothesis that influenza A virus-specific T cells contribute to atherosclerotic plaque inflammation, which mediates the onset of plaque rupture. METHODS - T-cell cultures were generated from atheroscleroti...

  4. Evaluating intensity normalization for multispectral classification of carotid atherosclerotic plaque

    Science.gov (United States)

    Gao, Shan; van't Klooster, Ronald; van Wijk, Diederik F.; Nederveen, Aart J.; Lelieveldt, Boudewijn P. F.; van der Geest, Rob J.

    2015-03-01

    Intensity normalization is an important preprocessing step for automatic plaque analysis in MR images as most segmentation algorithms require the images to have a standardized intensity range. In this study, we derived several intensity normalization approaches with inspiration from expert manual analysis protocols, for classification of carotid vessel wall plaque from in vivo multispectral MRI. We investigated intensity normalization based on a circular region centered at lumen (nCircle); based on sternocleidomastoid muscle (nSCM); based on intensity scaling (nScaling); based on manually classified fibrous tissue (nManuFibrous) and based on automatic classified fibrous tissue (nAutoFibrous). The proposed normalization methods were evaluated using three metrics: (1) Dice similarity coefficient (DSC) between manual and automatic segmentation obtained by classifiers using different normalizations; (2) correlation between proposed normalizations and normalization used by expert; (3) Mahalanobis Distance between pairs of components. In the performed classification experiments, features of normalized image, smoothed, gradient magnitude and Laplacian images at multi-scales, distance to lumen, distance to outer wall, wall thickness were calculated for each vessel wall (VW) pixel. A supervised pattern recognition system, based on a linear discriminate classifier, was trained using the manual segmentation result to classify each VW pixel to be one of the four classes: fibrous tissue, lipid, calcification, and loose matrix according to the highest posterior probability. We evaluated our method on image data of 23 patients. Compared to the result of conventional square region based intensity normalizatio n, nScaling resulted in significant increase in DSC for lipid (p = 0.006) and nAutoFibrous resulted in significant increase in DSC for calcification (p = 0.004). In conclusion, it was demonstrated that the conventional region based normalization approach is not optimal and n

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

    Science.gov (United States)

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

    2015-01-01

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

  6. IL-19 Halts Progression of Atherosclerotic Plaque, Polarizes, and Increases Cholesterol Uptake and Efflux in Macrophages.

    Science.gov (United States)

    Gabunia, Khatuna; Ellison, Stephen; Kelemen, Sheri; Kako, Farah; Cornwell, William D; Rogers, Thomas J; Datta, Prasun K; Ouimet, Mireille; Moore, Kathryn J; Autieri, Michael V

    2016-05-01

    Atherosclerosis regression is an important clinical goal, and treatments that can reverse atherosclerotic plaque formation are actively being sought. Our aim was to determine whether administration of exogenous IL-19, a Th2 cytokine, could attenuate progression of preformed atherosclerotic plaque and to identify molecular mechanisms. LDLR(-/-) mice were fed a Western diet for 12 weeks, then administered rIL-19 or phosphate-buffered saline concomitant with Western diet for an additional 8 weeks. Analysis of atherosclerosis burden showed that IL-19-treated mice were similar to baseline, in contrast to control mice which showed a 54% increase in plaque, suggesting that IL-19 halted the progression of atherosclerosis. Plaque characterization showed that IL-19-treated mice had key features of atherosclerosis regression, including a reduction in macrophage content and an enrichment in markers of M2 macrophages. Mechanistic studies revealed that IL-19 promotes the activation of key pathways leading to M2 macrophage polarization, including STAT3, STAT6, Kruppel-like factor 4, and peroxisome proliferator-activated receptor γ, and can reduce cytokine-induced inflammation in vivo. We identified a novel role for IL-19 in regulating macrophage lipid metabolism through peroxisome proliferator-activated receptor γ-dependent regulation of scavenger receptor-mediated cholesterol uptake and ABCA1-mediated cholesterol efflux. These data show that IL-19 can halt progression of preformed atherosclerotic plaques by regulating both macrophage inflammation and cholesterol homeostasis and implicate IL-19 as a link between inflammation and macrophage cholesterol metabolism. PMID:26952642

  7. Magnetic resonance imaging features of vulnerable plaques in an atherosclerotic rabbit model

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xue-cheng; ZHAO Quan-ming; MA Xiao-hai; ZENG Cong-he; FENG Ting-ting; ZHAO Xin; ZHANG Zhao-qi

    2013-01-01

    Background Noninvasive detection of vulnerable plaque has a significant implication for prevention and treatment of atherosclerotic diseases.The aim of this study is to investigate the difference between vulnerable plaques and stable plaques in magnetic resonance (MR) images.Methods Atherosclerosis was induced in twenty male New Zealand white rabbits by high cholesterol diet and balloon injury of the abdominal aorta.After baseline (pre-triggering) MR imaging (MRI) scan,the rabbits underwent pharmaceutical triggering with Russell's viper venom and histamine to induce atherothrombosis,followed by another MRI scan 48 hours later (post-triggering).Rabbits were euthanized to obtain pathological and histological data.The results of MRI were compared with those of pathology and histology.Results MRI showed that abdominal aorta of the rabbits had pathological change of atherosclerosis in different degrees.Seventy-five plaques were analysed,among which 14 had vulnerable thrombi and 61 stable.Thrombosis was identified in 7 of 11 rabbits by post-triggering MRI,the sensitivity and K value of MR in detection of vulnerable plaque was 71% and 0.803 (P <0.05).MRI data significantly correlated with the histopathological data in fibrous cap thickness (t=0.749) plaque area (r=0.853),lipid core area (r=0.900).Compared with stable plaques,vulnerable plaques had a significantly thinner fibrous cap ((0.58+0.27) mm vs.(0.95+0.22) mm),larger lipid core area ((7.56+2.78) mm2 vs.(3.29+1.75) mm2),and a higher ratio of lipid core area/plaque area ((55+16)% vs.(27±17)%),but plaque area was comparable in two groups on MRI.The ratio of lipid core area/plaque area was a strong predictor of vulnerable plaques.Conclusion MRI could distinguish vulnerable plaques from stable plaques in a rabbit model of atherothrombosis and may thus be useful as a noninvasive modality for detection of vulnerable plaques in humans.

  8. Phage Display Identification of CD100 in Human Atherosclerotic Plaque Macrophages and Foam Cells

    OpenAIRE

    Luque, Maria Carolina Aquino; Gutierrez, Paulo Sampaio; Debbas, Victor; Martins, Waleska Kerllen; Puech-Leao, Pedro; Porto, Georgia; Coelho, Verônica; Boumsell, Laurence; Kalil, Jorge; Stolf, Beatriz

    2013-01-01

    Atherosclerosis is a complex disease in which vessels develop plaques comprising dysfunctional endothelium, monocyte derived lipid laden foam cells and activated lymphocytes. Considering that humans and animal models of the disease develop quite distinct plaques, we used human plaques to search for proteins that could be used as markers of human atheromas. Phage display peptide libraries were probed to fresh human carotid plaques, and a bound phage homologous to plexin B1, a high affinity rec...

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

    International Nuclear Information System (INIS)

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

  10. IVUS-based histology of atherosclerotic plaques: improving longitudinal resolution

    Science.gov (United States)

    Taki, Arash; Pauly, Olivier; Setarehdan, S. Kamaledin; Unal, Gozde; Navab, Nassir

    2010-03-01

    Although Virtual Histology (VH) is the in-vivo gold standard for atherosclerosis plaque characterization in IVUS images, it suffers from a poor longitudinal resolution due to ECG-gating. In this paper, we propose an image-based approach to overcome this limitation. Since each tissue have different echogenic characteristics, they show in IVUS images different local frequency components. By using Redundant Wavelet Packet Transform (RWPT), IVUS images are decomposed in multiple sub-band images. To encode the textural statistics of each resulting image, run-length features are extracted from the neighborhood centered on each pixel. To provide the best discrimination power according to these features, relevant sub-bands are selected by using Local Discriminant Bases (LDB) algorithm in combination with Fisher's criterion. A structure of weighted multi-class SVM permits the classification of the extracted feature vectors into three tissue classes, namely fibro-fatty, necrotic core and dense calcified tissues. Results shows the superiority of our approach with an overall accuracy of 72% in comparison to methods based on Local Binary Pattern and Co-occurrence, which respectively give accuracy rates of 70% and 71%.

  11. Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Ikuko, E-mail: nakamuri@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Cardiovascular Medicine, Saga University, Saga (Japan); Hasegawa, Koki [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Pathology and Experimental Medicine, Kumamoto University, Kumamoto (Japan); Wada, Yasuhiro [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Hirase, Tetsuaki; Node, Koichi [Department of Cardiovascular Medicine, Saga University, Saga (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan)

    2013-03-29

    Highlights: ► P-selectin regulates leukocyte recruitment as an early stage event of atherogenesis. ► We developed an antibody-based molecular imaging probe targeting P-selectin for PET. ► This is the first report on successful PET imaging for delineation of P-selectin. ► P-selectin is a candidate target for atherosclerotic plaque imaging by clinical PET. -- Abstract: Background: Sensitive detection and qualitative analysis of atherosclerotic plaques are in high demand in cardiovascular clinical settings. The leukocyte–endothelial interaction mediated by an adhesion molecule P-selectin participates in arterial wall inflammation and atherosclerosis. Methods and results: A {sup 64}Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated anti-P-selectin monoclonal antibody ({sup 64}Cu-DOTA-anti-P-selectin mAb) probe was prepared by conjugating an anti-P-selectin monoclonal antibody with DOTA followed by {sup 64}Cu labeling. Thirty-six hours prior to PET and CT fusion imaging, 3 MBq of {sup 64}Cu-DOTA-anti-P-selectin mAb was intravenously injected into low density lipoprotein receptor-deficient Ldlr-/- mice. After a 180 min PET scan, autoradiography and biodistribution of {sup 64}Cu-DOTA-anti-P-selectin monoclonal antibody was examined using excised aortas. In Ldlr-/- mice fed with a high cholesterol diet for promotion of atherosclerotic plaque development, PET and CT fusion imaging revealed selective and prominent accumulation of the probe in the aortic root. Autoradiography of aortas that demonstrated probe uptake into atherosclerotic plaques was confirmed by Oil red O staining for lipid droplets. In Ldlr-/- mice fed with a chow diet to develop mild atherosclerotic plaques, probe accumulation was barely detectable in the aortic root on PET and CT fusion imaging. Probe biodistribution in aortas was 6.6-fold higher in Ldlr-/- mice fed with a high cholesterol diet than in those fed with a normal chow diet. {sup 64}Cu-DOTA-anti-P-selectin m

  12. MRI-based Biomechanical Modeling of Carotid Atherosclerotic Plaques: The stable plaque paradigm

    OpenAIRE

    Nieuwstadt, Harm

    2015-01-01

    markdownabstract__Abstract__ Carotid atherosclerosis is a common cause of acute ischemic stroke and places a major burden on worldwide health-related quality of life. The currently-used stenosis-degree guidelines to decide on surgical intervention through carotid endarterectomy in order to prevent a future event are imperfect. This is because they insufficiently target plaque vulnerability. To provide an alternative carotid plaque vulnerability assessment, one can compute the biomechanical pe...

  13. Ex vivo identification of atherosclerotic plaque calcification by a 31P solid-state magnetic resonance imaging technique.

    Science.gov (United States)

    Hallock, Kevin J; Hamilton, James A

    2006-12-01

    Calcified tissue is a common component of atherosclerotic plaques, and occurs most often in mature plaques. The process of calcification is a poorly understood risk factor that may contribute to a plaque's vulnerability to sudden rupture. In this study a solid-state imaging sequence, termed single-point imaging (SPI), was used to observe calcification directly in ex vivo atherosclerotic plaques. Standards were used to validate the ability of (31)P SPI to detect and differentiate calcification from crystalline cholesterol, phospholipids, and other plaque components. After suitable experimental parameters were found, human carotid specimens obtained by endarterectomy were imaged ex vivo by (31)P solid-state imaging and standard (1)H methods. In contrast to (1)H imaging methods, (31)P imaging detected only the calcification in the plaque. PMID:17089379

  14. The Role of Septal Perforators and “Myocardial Bridging Effect” in Atherosclerotic Plaque Distribution in the Coronary Artery Disease

    OpenAIRE

    Wasilewski, Jarosław; Roleder, Marcin; Niedziela, Jacek; Nowakowski, Andrzej; Osadnik, Tadeusz; Głowacki, Jan; Mirota, Kryspin; Poloński, Lech

    2015-01-01

    Summary The distribution of atherosclerotic plaque burden in the human coronary arteries is not uniform. Plaques are located mostly in the left anterior descending artery (LAD), then in the right coronary artery (RCA), circumflex branch (LCx) and the left main coronary artery (LM) in a decreasing order of frequency. In the LAD and LCx, plaques tend to cluster within the proximal segment, while in the RCA their distribution is more uniform. Several factors have been involved in this phenomenon...

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

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Rosendal, Kim; Grønholdt, Marie-Louise Moes; Jespersen, Søren Kragh; Hansen, Lars Kai; Sillesen, Henrik

    This paper reports on a study of how well texture features extracted from B-mode images of atherosclerotic plaque correlates with histological results obtained from the same plaque after carotid endarterectomy. The study reveals that a few second order texture features (diagonal moment, standard...... deviation and autocorrelation) provide good correlation within the training set (p = 0.04); However, the correlation found so far is not so high, that the method can be used in clinical prediction of plaque constituents....

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

    Science.gov (United States)

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

    2011-03-01

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

  17. Wall shear stress as a stimulus for carotid atherosclerotic plaque progression: An MRI-based CFD pilot study

    Science.gov (United States)

    Canton, Gador; Chiu, Bernard; Hatsukami, Tom; Kerwin, William; Yuan, Chun

    2010-11-01

    The aim of this study was to explore the hypothesis that intra-plaque hemorrhage, a feature associated with adverse outcomes and atherosclerotic plaque progression and destabilization, is more likely to occur in plaques with elevated levels of wall shear stress (WSS). We used multi-sequence in-vivo magnetic resonance imaging (MRI) to characterize ten human carotid atherosclerotic plaques and an MRI-based computational fluid dynamics (CFD) model to solve the equations governing the blood flow. Hemorrhage was detected within the necrotic core (intra-plaque hemorrhage) in five of these ten cases. WSS data were extracted from the results of the CFD simulations to compare patterns between the cases with and without hemorrhage. We computed the mean value of the WSS (for each time point of the cardiac cycle) at the region where a necrotic core was detected. The results from this pilot study indicate a possible link between the presence of hemorrhage within a lipid-rich necrotic core in human carotid atherosclerotic plaques and elevated levels of shear stress force acting on the luminal surface. Thus, elevated wall shear stress may be used as a high risk feature in advanced carotid atherosclerotic plaques.

  18. Comparison between Adventitial and Intimal Inflammation of Ruptured and Nonruptured Atherosclerotic Plaques in Human Coronary Arteries

    Directory of Open Access Journals (Sweden)

    Higuchi Maria L.

    2002-01-01

    Full Text Available OBJECTIVE: To verify the possible role of adventitial inflammation in atherosclerotic plaque vulnerability and coronary artery remodelling. METHODS: We compared the mean numbers of lymphocytes in the adventitia and in the plaque of ruptured thrombosed and stable equi-stenotic coronary segments of 34 patients who died due to acute myocardial infarction. We also analysed adventitial microvessels, adventitial fibrosis and the external elastic membrane. RESULTS: In the adventitia, the numbers of lymphocytes and microvessels/mm² were 69.5±88.3 and 60.9± 32.1 in culprit lesions and 16.4 ± 21.1 and 44.3±16.1 in stable lesions (p<0.05; within the plaques, the mean number of lymphocytes was 24±40.8 in culprit lesions and 10.9±13.2 in stable ones (p=0.17. The mean percent area of adventitial fibrosis/cross-sectional area of the vessel was significantly lower in unstable plaques (p<0.001. The confocal images showed holes in the external elastic membrane. CONCLUSION: Unstable plaques exhibit chronic pan-arteritis, accompanied by enlargement, medial thinning, and less fibrosis than in stable lesions, which is compatible with vessel aneurysm. Adventitial inflammation may contribute significantly to atheroma instability.

  19. Echolucency of computerized ultrasound images of carotid atherosclerotic plaques are associated with increased levels of triglyceride-rich lipoproteins as well as increased plaque lipid content

    DEFF Research Database (Denmark)

    Grønholdt, Marie-Louise M.; Nordestgaard, Børge; Wiebe, Britt M.; Wilhjelm, Jens Erik; Sillesen, Henrik

    1998-01-01

    Background-Echo-lucency of carotid atherosclerotic plaques on computerized ultrasound B-mode images has been associated with a high incidence of brain infarcts as evaluated on CT scans. We tested the hypotheses that triglyceride-rich lipoproteins in the fasting and postprandial state predict......-rich lipoproteins predict echo-lucency of carotid plaques, which is associated with increased plaque Lipid content, Because echo-lucency has been associated with a high incidence of brain infarcts on CT scans, triglyceride-rich lipoproteins may predict a plaque type particularly vulnerable to rupture....

  20. An integrated system for the segmentation of atherosclerotic carotid plaque ultrasound video.

    Science.gov (United States)

    Loizou, Christos; Petroudi, Styliani; Pantziaris, Marios; Nicolaides, Andrew; Pattichis, Constantinos

    2014-01-01

    The robust border identification of atherosclerotic carotid plaque, the corresponding degree of stenosis of the common carotid artery (CCA), and also the characteristics of the arterial wall, including plaque size, composition, and elasticity, have significant clinical relevance for the assessment of future cardiovascular events. To facilitate the follow-up and analysis of the carotid stenosis in serial clinical investigations, we propose and evaluate an integrated system for the segmentation of atherosclerotic carotid plaque in ultrasound videos of the CCA based on video frame normalization, speckle reduction filtering, M-mode state-based identification, parametric active contours, and snake segmentation. Initially, the cardiac cycle in each video is identified and the video M-mode is generated, thus identifying systolic and diastolic states. The video is then segmented for a time period of at least one full cardiac cycle. The algorithm is initialized in the first video frame of the cardiac cycle, with human assistance if needed, and the moving atherosclerotic plaque borders are tracked and segmented in the subsequent frames. Two different initialization methods are investigated in which initial contours are estimated every 20 video frames. In the first initialization method, the initial snake contour is estimated using morphology operators; in the second initialization method, the Chan-Vese active contour model is used. The performance of the algorithm is evaluated on 43 real CCA digitized videos from B-mode longitudinal ultrasound segments and is compared with the manual segmentations of an expert, available every 20 frames in a time span of 3 to 5 s, covering, in general, 2 cardiac cycles. The segmentation results were very satisfactory, according to the expert objective evaluation, for the two different methods investigated, with true-negative fractions (TNF-specificity) of 83.7 ± 7.6% and 84.3 ± 7.5%; true-positive fractions (TPF-sensitivity) of 85.42 ± 8

  1. Aortic atherosclerotic plaque detection using a multiwavelength handheld photoacoustic imaging system

    Science.gov (United States)

    Hirano, Susumu; Namita, Takeshi; Kondo, Kengo; Yamakawa, Makoto; Shiina, Tsuyoshi

    2016-03-01

    Patients affected by diseases caused by arteriosclerosis are increasing. Atherosclerosis, which is becoming an especially difficult health problem, forms plaques from lipids such as cholesterol located in walls of the aorta, cerebral artery, and coronary artery. Because lipid-rich plaques are vulnerable and because arterial rupture causes acute vascular occlusion, early detection is crucially important to prevent plaque growth and rupture. Ultrasound systems can detect plaques but cannot discriminate between vulnerable and equable plaques. To evaluate plaques non-invasively and easily, we developed a handheld photoacoustic imaging device. Its usefulness was verified in phantom experiments with a bovine aorta in which mimic plaque had been embedded. Photoacoustic images taken at wavelengths that produce high light absorbance by lipids show strong photoacoustic signals from the boundary of the mimic plaque. Results confirmed that our system can evaluate plaque properties by analysis with the photoacoustic spectrum. The effects of surrounding tissues and tissue components on plaque evaluation were investigated using a layered phantom. The mimic plaque located under a 6 mm blood layer was also evaluated. Results of these analyses demonstrate the system's usefulness.

  2. Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques

    Directory of Open Access Journals (Sweden)

    Fagerberg Björn

    2005-08-01

    Full Text Available Abstract Background The protective role of high-density lipoprotein (HDL in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. Methods The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL, two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15 and healthy controls (n = 15. Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. Results SR-BI expression was decreased in macrophages after hypoxia (p Conclusion We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.

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

    OpenAIRE

    Kalanuria AA; Nyquist P; Ling G

    2012-01-01

    Atul Ashok Kalanuria,1 Paul Nyquist,1 Geoffrey Ling1,21Division of Neuro Critical Care, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, 2Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, USAAbstract: Occlusive vascular diseases, such as sudden coronary syndromes, stroke, and peripheral arterial disease, are a huge burden on the health care systems of developed and developing countri...

  4. Assessment of 320-slice computed tomography angiography in distinguishing hemorrhage in carotid atherosclerotic plaques

    OpenAIRE

    Zhang, Xiao-Jie; Yu, Wei; Tao BI; Zi-xu YAN; Feng-ru SHI; SUN, Li-yuan; Zhao-qi ZHANG

    2014-01-01

    Objective To assess the value of 320⁃slice computed tomography angiography (CTA) in distinguishing hemorrhage/thrombus from lipid-rich necrotic core (LRNC) in atherosclerotic plaques of carotid artery. Methods Thirty-seven subjects who prepared to perform carotid endarterectomy (CEA), with stenosis rate about 50%-99% in at least unilateral carotid artery detected by ultrasound, were enrolled in this study. Both 320-slice CTA and 3.0T high-resolution MRI were conducted within one week before o...

  5. Meshless Generalized Finite Difference Method and Human Carotid Atherosclerotic Plaque Progression Simulation Using Multi-Year MRI Patient-Tracking Data

    OpenAIRE

    Yang, Chun; Tang, Dalin; Yuan, Chun; Kerwin, William; Liu, Fei; Canton, Gador; Hatsukami, Thomas S.; Atluri, Satya

    2008-01-01

    Atherosclerotic plaque rupture and progression have been the focus of intensive investigations in recent years. Plaque rupture is closely related to most severe cardiovascular syndromes such as heart attack and stroke. A computational procedure based on meshless generalized finite difference (MGFD) method and serial magnetic resonance imaging (MRI) data was introduced to quantify patient-specific carotid atherosclerotic plaque growth functions and simulate plaque progression. Participating pa...

  6. Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability

    International Nuclear Information System (INIS)

    Introduction: Atherosclerotic plaque rupture is the primary cause for myocardial infarction and stroke. During plaque progression macrophages and mast cells secrete matrix-degrading proteolytic enzymes, such as matrix metalloproteinases (MMPs). We studied levels of MMPs and tissue inhibitor of metalloproteinases-3 (TIMP-3) in relation to the characteristics of carotid plaques. We evaluated in vitro two radiolabeled probes targeting active MMPs towards non-invasive imaging of rupture-prone plaques. Methods: Human carotid plaques obtained from endarterectomy were classified into stable and vulnerable by visual and histological analysis. MMP-1, MMP-2, MMP-8, MMP-9, MMP-10, MMP-12, MMP-14, TIMP-3, and CD68 levels were investigated by quantitative polymerase chain reaction. Immunohistochemistry was used to localize MMP-2 and MMP-9 with respect to CD68-expressing macrophages. Western blotting was applied to detect their active forms. A fluorine-18-labeled MMP-2/MMP-9 inhibitor and a tritiated selective MMP-9 inhibitor were evaluated by in vitro autoradiography as potential lead structures for non-invasive imaging. Results: Gene expression levels of all MMPs and CD68 were elevated in plaques. MMP-1, MMP-9, MMP-12 and MMP-14 were significantly higher in vulnerable than stable plaques. TIMP-3 expression was highest in stable and low in vulnerable plaques. Immunohistochemistry revealed intensive staining of MMP-9 in vulnerable plaques. Western blotting confirmed presence of the active form in plaque lysates. In vitro autoradiography showed binding of both inhibitors to stable and vulnerable plaques. Conclusions: MMPs differed in their expression patterns among plaque phenotypes, providing possible imaging targets. The two tested MMP-2/MMP-9 and MMP-9 inhibitors may be useful to detect atherosclerotic plaques, but not the vulnerable lesions selectively

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Sezer ED

    2011-06-01

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

  9. Significance of ultrasound evaluation of carotid atherosclerotic plaque for diagnosing ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Carotid artery is the main source for craniocerebral blood supply. Its intimal plaque formation and arterial stenosis degree both are the risk factors for ischemic cerebrovascular disease.Therefore, the close relationship of carotid atherosclerotic plaque and ischemic cerebrovascular disease, and ultrasound evaluation of carotid atherosclerotic plaque have become the hot spot in studying ischemic cerebrovascular disease.OBJECTIVE: This study was to detect the degree of carotid atherosclerosis of ischemic cerebrovascular disease patients by ultrasonography, and to analyze the situation of carotid atherosclerosis and its relationship with clinic.DESIGN: Clinical randomized concurrent control experiment.SETTING: Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS: Totally 60 outpatients and inpatients with ischemic cerebrovascular disease, 42 males and 18 females, admitted to Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA between January 2006 and December 2006 were involved in the patient group. They met the diagnosis criteria of ischemic cerebrovascular disease constituted by the 4th Cerebrovascular Disease Conference in 1996, and were confirmed to suffer from ischemic cerebrovascular disease by skull CT and MRI. Another 20 subjects who received healthy examination concurrently in the same hospital, 12 males and 8 females, were involved in the control group. Informed consents of detected items were obtained from involved subjects.METHODS: The plaque thickness of mid portion, distal end and crotch of common carotid artery (CCA),internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA) of involved subjects,who received health examination was separately detected with color Doppler ultrasonograph (HDI-5000).Then, total integral of plaque was calculated. The intima-media thickness (IMT) was measured with two-dimensional ultrasonography. The inner diameter

  10. Combined micro-PIXE and NIR Raman spectroscopic plaque characterisation in a human atherosclerotic aorta sample

    International Nuclear Information System (INIS)

    Raman spectroscopy can be applied to characterise the chemical composition of an atherosclerotic plaque in vivo. In the near future this technique may become available for use in (coronary) arteries of living patients. For this moment, Raman spectroscopy is applied on artery samples in vitro, to study progression and regression of atherosclerotic plaque. Raman spectroscopy provides chemical information on a molecular basis. In this study, micro-particle induced X-ray emission (micro-PIXE) is applied to provide additional information on the elemental composition of the artery. Furthermore, the combined techniques allow for validation of the structures studied with Raman spectroscopy. This study proves that it is possible to combine and compare both techniques using the same region on the same sample if proper sample preparation is applied. Comparison shows that regions appearing in the Raman spectroscopy results can also be distinguished in micro-PIXE and backscattering spectroscopy (BS) distributions and vice versa. Combining both techniques makes it possible to separate phospholipids from triglycerides. Combined Raman spectroscopy and micro-PIXE/BS is recommended for studying progression and regression of atherosclerosis

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

    Institute of Scientific and Technical Information of China (English)

    霍煜

    2014-01-01

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

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

    Science.gov (United States)

    van Engelen, Arna; Niessen, Wiro J; Klein, Stefan; Groen, Harald C; Verhagen, Hence J M; Wentzel, Jolanda J; van der Lugt, Aad; de Bruijne, Marleen

    2014-01-01

    Atherosclerotic plaque composition can indicate plaque vulnerability. We segment atherosclerotic plaque components from the carotid artery on a combination of in vivo MRI and CT-angiography (CTA) data using supervised voxelwise classification. In contrast to previous studies the ground truth for training is directly obtained from 3D registration with histology for fibrous and lipid-rich necrotic tissue, and with μCT for calcification. This registration does, however, not provide accurate voxelwise correspondence. We therefore evaluate three approaches that incorporate uncertainty in the ground truth used for training: I) soft labels are created by Gaussian blurring of the original binary histology segmentations to reduce weights at the boundaries between components, and are weighted by the estimated registration accuracy of the histology and in vivo imaging data (measured by overlap), II) samples are weighted by the local contour distance of the lumen and outer wall between histology and in vivo data, and III) 10% of each class is rejected by Gaussian outlier rejection. Classification was evaluated on the relative volumes (% of tissue type in the vessel wall) for calcified, fibrous and lipid-rich necrotic tissue, using linear discriminant (LDC) and support vector machine (SVM) classification. In addition, the combination of MRI and CTA data was compared to using only one imaging modality. Best results were obtained by LDC and outlier rejection: the volume error per vessel was 0.9±1.0% for calcification, 12.7±7.6% for fibrous and 12.1±8.1% for necrotic tissue, with Spearman rank correlation coefficients of 0.91 (calcification), 0.80 (fibrous) and 0.81 (necrotic). While segmentation using only MRI features yielded low accuracy for calcification, and segmentation using only CTA features yielded low accuracy for necrotic tissue, the combination of features from MRI and CTA gave good results for all studied components. PMID:24762678

  13. MRI of the transplanted endothelial progenitor cells for prevent atherosclerotic plaque formation

    International Nuclear Information System (INIS)

    Objective: To evaluate the 1.5 T magnetic resonance imaging system to depict and track in vivo of magnetically labeled endothelial progenitor cells (EPCs), and to study the possibility for preventing the atherosclerotic plaque formation in New Zealand rabbit model of carotid arterial injury after transplantation. Methods: New Zealand rabbit EPCs were isolated, confirmed, expanded and then incubated with home synthesized Fe2O3-PLL, Prussian blue stain was performed for showing intracellular irons. The model of carotid arterial injury was performed by 2.5F balloons, the group A of 8 rabbits received magnetically labeled EPCs, group B of 3 rabbits received fluorescent-labeled EPCs and the group C of 5 rabbits were given same volume saline injection after endothelial injury of the carotid artery. MR imaging and histology were performed and compared 4 days later for randomly chosen three rabbit, each from one of the three group; all the other rabbits were fed with high lipid diet and examed using MR imaging and histology after 15 weeks. Results: Epcs labeling efficiency was more than 95% by Prussian blue stain, 4 days after transplantation of EPCs, only in group A, the injured endothelium of carotid artery had signal intensity loss in T2*WI, which were correlated well with the area where the most Prussian blue staining positive cells were found in histopathology analyses. The rabbits of group A and B which received EPCs transplantation exhibited fewer plaques formation than those of the group C (P2O3-PLL. The 1.5 T magnetic resonance imaging system could depict and monitor the magnetically labeled endothelial progenitor cells homing to the injured endothelium of the artery, and EPCs contribute to preventing atherosclerotic plaque formation in New Zealand rabbit model of atherosclerosis. (authors)

  14. Characterization of signal properties in atherosclerotic plaque components by intravascular MRI.

    Science.gov (United States)

    Rogers, W J; Prichard, J W; Hu, Y L; Olson, P R; Benckart, D H; Kramer, C M; Vido, D A; Reichek, N

    2000-07-01

    Magnetic resonance imaging (MRI) is capable of distinguishing between atherosclerotic plaque components solely on the basis of biochemical differences. However, to date, the majority of plaque characterization has been performed by using high-field strength units or special coils, which are not clinically applicable. Thus, the purpose of the present study was to evaluate MRI properties in histologically verified plaque components in excised human carotid endarterectomy specimens with the use of a 5F catheter-based imaging coil, standard acquisition software, and a clinical scanner operating at 0.5 T. Human carotid endarterectomy specimens from 17 patients were imaged at 37 degrees C by use of an opposed solenoid intravascular radiofrequency coil integrated into a 5F double-lumen catheter interfaced to a 0.5-T General Electric interventional scanner. Cross-sectional intravascular MRI (156x250 microm in-plane resolution) that used different imaging parameters permitted the calculation of absolute T1and T2, the magnetization transfer contrast ratio, the magnitude of regional signal loss associated with an inversion recovery sequence (inversion ratio), and regional signal loss in gradient echo (gradient echo-to-spin echo ratio) in plaque components. Histological staining included hematoxylin and eosin, Masson's trichrome, Kossa, oil red O, and Gomori's iron stain. X-ray micrographs were also used to identify regions of calcium. Seven plaque components were evaluated: fibrous cap, smooth muscle cells, organizing thrombus, fresh thrombus, lipid, edema, and calcium. The magnetization transfer contrast ratio was significantly less in the fibrous cap (0.62+/-13) than in all other components (Psmooth muscle cells) were not significantly different between groups. In vitro intravascular MRI with catheter-based coils and standard software permits sufficient spatial resolution to visualize major plaque components. Pulse sequences that take advantage of differences in biochemical

  15. Magnetization transfer magnetic resonance of human atherosclerotic plaques ex vivo detects areas of high protein density

    Directory of Open Access Journals (Sweden)

    Qiao Ye

    2011-11-01

    Full Text Available Abstract Background Proteins are major plaque components, and their degradation is related to the plaque instability. We sought to assess the feasibility of magnetization transfer (MT magnetic resonance (MR for identifying fibrin and collagen in carotid atherosclerotic plaques ex vivo. Methods Human carotid artery specimens (n = 34 were obtained after resection from patients undergoing endarterectomy. MR was completed within 12 hr after surgery on an 11.7T MR microscope prior to fixation. Two sets of T1W spoiled gradient echo images were acquired with and without the application of a saturation pulse set to 10 kHz off resonance. The magnetization transfer ratio (MTR was calculated, and the degree of MT contrast was correlated with histology. Results MT with appropriate calibration clearly detected regions with high protein density, which showed a higher MTR (thick fibers (collagen type I (54 ± 8% compared to regions with a low amount of protein including lipid (46 ± 8% (p = 0.05, thin fibers (collagen type III (11 ± 6% (p = 0.03, and calcification (6.8 ± 4% (p = 0.02. Intraplaque hemorrhage (IPH with different protein density demonstrated different MT effects. Old (rich in protein debris and recent IPH (rich in fibrin had a much higher MTR 69 ± 6% and 55 ± 9%, respectively, compared to fresh IPH (rich in intact red blood cells(9 ± 3%. Conclusions MT MR enhances plaque tissue contrast and identifies the protein-rich regions of carotid artery specimens. The additional information from MTR of IPH may provide important insight into the role of IPH on plaque stability, evolution, and the risk for future ischemic events.

  16. Assessment of atherosclerotic plaque vulnerability of coronary arteries in cases of sudden cardiac death

    International Nuclear Information System (INIS)

    To study the plaque vulnerability in coronary arteries taken from autopsy specimens, of individuals dying of ischemic heart disease in our setup and to compare it with atheroma of those who died of non-cardiac causes. Sixty coronary arteries having atherosclerosis, from autopsies of patients who died of sudden cardiac death were divided into case and control groups. Case group included thirty coronary arteries having atherosclerosis from autopsies of patients of whose death was attributable to Ischemic Heart Disease (IHD). Control group included thirty coronary arteries where atherosclerotic changes were found by chance (death not attributable to ischemic heart disease). Plaques were assessed for fibrous cap thickness, foam cells; mean percentage of inflammatory cells on Haemotoxylin and Eosin (H and E) stained slides whereas immunohistochemical (IHC) markers for T-Cells were done by IHC stain method. In present study, foam cells are significantly more in study group than in control group (P=0.007). Fibrous cap thickness fulfilling the criteria of vulnerable plaque was more in study group as compared to control group (P<0.001). The present study demonstrated that there was insignificant difference (P=0.152), in the mean percentage of inflammatory cells in case group and control group. An overall significant association was found between vulnerable plaque and death due to ischemic heart disease (P<0.001). Conclusion: Patients dying of ischemic heart disease have more vulnerable plaque in their coronary arteries as compared to those dying from non ischemic cause. Although this is an autopsy study but the significance of in this study can be very important to guide cardiologists to identify patients at high risk of acute coronary syndrome and use new diagnostic modalities like intravascular ultrasonography and therapeutic strategies like genomic and proteomic techniques. This will help the early detection and treatment of such cases and may ultimately reduce the

  17. Support vector machine based classification and mapping of atherosclerotic plaques using fluorescence lifetime imaging (Conference Presentation)

    Science.gov (United States)

    Fatakdawala, Hussain; Gorpas, Dimitris S.; Bec, Julien; Ma, Dinglong M.; Yankelevich, Diego R.; Bishop, John W.; Marcu, Laura

    2016-02-01

    The progression of atherosclerosis in coronary vessels involves distinct pathological changes in the vessel wall. These changes manifest in the formation of a variety of plaque sub-types. The ability to detect and distinguish these plaques, especially thin-cap fibroatheromas (TCFA) may be relevant for guiding percutaneous coronary intervention as well as investigating new therapeutics. In this work we demonstrate the ability of fluorescence lifetime imaging (FLIm) derived parameters (lifetime values from sub-bands 390/40 nm, 452/45 nm and 542/50 nm respectively) for generating classification maps for identifying eight different atherosclerotic plaque sub-types in ex vivo human coronary vessels. The classification was performed using a support vector machine based classifier that was built from data gathered from sixteen coronary vessels in a previous study. This classifier was validated in the current study using an independent set of FLIm data acquired from four additional coronary vessels with a new rotational FLIm system. Classification maps were compared to co-registered histological data. Results show that the classification maps allow identification of the eight different plaque sub-types despite the fact that new data was gathered with a different FLIm system. Regions with diffuse intimal thickening (n=10), fibrotic tissue (n=2) and thick-cap fibroatheroma (n=1) were correctly identified on the classification map. The ability to identify different plaque types using FLIm data alone may serve as a powerful clinical and research tool for studying atherosclerosis in animal models as well as in humans.

  18. A Framework for Local Mechanical Characterization of Atherosclerotic Plaques: Combination of Ultrasound Displacement Imaging and Inverse Finite Element Analysis.

    Science.gov (United States)

    Akyildiz, Ali C; Hansen, Hendrik H G; Nieuwstadt, Harm A; Speelman, Lambert; De Korte, Chris L; van der Steen, Antonius F W; Gijsen, Frank J H

    2016-04-01

    Biomechanical models have the potential to predict plaque rupture. For reliable models, correct material properties of plaque components are a prerequisite. This study presents a new technique, where high resolution ultrasound displacement imaging and inverse finite element (FE) modeling is combined, to estimate material properties of plaque components. Iliac arteries with plaques were excised from 6 atherosclerotic pigs and subjected to an inflation test with pressures ranging from 10 to 120 mmHg. The arteries were imaged with high frequency 40 MHz ultrasound. Deformation maps of the plaques were reconstructed by cross correlation of the ultrasound radiofrequency data. Subsequently, the arteries were perfusion fixed for histology and structural components were identified. The histological data were registered to the ultrasound data to construct FE model of the plaques. Material properties of the arterial wall and the intima of the atherosclerotic plaques were estimated using a grid search method. The computed displacement fields showed good agreement with the measured displacement fields, implying that the FE models were able to capture local inhomogeneities within the plaque. On average, nonlinear stiffening of both the wall and the intima was observed, and the wall of the atheroslcerotic porcine iliac arteries was markedly stiffer than the intima (877 ± 459 vs. 100 ± 68 kPa at 100 mmHg). The large spread in the data further illustrates the wide variation of the material properties. We demonstrated the feasibility of a mixed experimental-numerical framework to determine the material properties of arterial wall and intima of atherosclerotic plaques from intact arteries, and concluded that, due to the observed variation, plaque specific properties are required for accurate stress simulations. PMID:26399991

  19. Comparison of MRI and DSA in assessment of carotid artery stenosis and atherosclerotic plaque

    International Nuclear Information System (INIS)

    Objective: To compare the efficacy of MRI and DSA in assessment of carotid artery stenosis and atherosclerotic plaque. Methods: Forty-six patients with carotid plaque detected by ultrasound were enrolled in this study, and 89 carotid arteries were evaluated by MRI and DSA. MRI examination was acquired with 3.0 T MR scanner and 8 channel phase-array surface coil. The MRI sequences consisted of pre-and post-contrast T1WI, T2WI, PDWI, TOF. Anterior-posterior and lateral views of carotid artery were performed on DSA. The degree of carotid artery stenosis was evaluated by the NASCET standard. Fibrous cap rupture, intraplaque hemorrhage, and calcification were also evaluated on MRI and DSA. Statistical comparison was performed with the Kappa value and paired Chi-square test. Results: The degree of carotid artery stenosis was 50% (16%-78%) on MRI and 47% (7%-73%) on DSA. Two imaging modalities were in good consistency in evaluation of the degree of stenosis (Kappa = 0.882, P2 =20.346, P<0.01). Furthermore, thirty-seven vessels with intraplaque hemorrhage and 71 vessels with calcification in the plaque were found on MRI but none on DSA. Conclusion: MRI is a reliable tool in assessment of the degree of the carotid stenosis and it is superior to DSA in detecting fibrous cap rupture, intraplaque hemorrhage, and calcification. (authors)

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    83-96% of the total oxidized protein side-chain products detected in these plaques. Oxidation of matrix components extracted from healthy artery tissue, and model proteins, with reagent HOCl is shown to give rise to a similar pattern of products to those detected in advanced human lesions. The......Oxidation is believed to play a role in atherosclerosis. Oxidized lipids, sterols and proteins have been detected in early, intermediate and advanced human lesions at elevated levels. The spectrum of oxidized side-chain products detected on proteins from homogenates of advanced human lesions has...... material obtained from advanced human atherosclerotic lesions are shown to contain elevated levels of oxidized amino acids [3,4-dihydroxyphenylalanine (DOPA), di-tyrosine, 2-hydroxyphenylalanine ( o-Tyr)] when compared with healthy (human and pig) arterial tissue. These matrix-derived materials account for...

  1. Biomechanics of atherosclerotic coronary plaque: site, stability and in vivo elasticity modeling.

    OpenAIRE

    Ohayon, Jacques; Finet, Gérard; Le Floc’h, Simon; Cloutier, Guy; Gharib, Ahmed M.; Heroux, Julie; Pettigrew, Roderic I.

    2014-01-01

    International audience Coronary atheroma develop in local sites that are widely variable among patients and are considerably variable in their vulnerability for rupture. This article summarizes studies conducted by our collaborative laboratories on predictive biomechanical modeling of coronary plaques. It aims to give insights into the role of biomechanics in the development and localization of atherosclerosis, the morphologic features that determine vulnerable plaque stability, and emergi...

  2. Painting blood vessels and atherosclerotic plaques with an adhesive drug depot

    Science.gov (United States)

    Kastrup, Christian J.; Nahrendorf, Matthias; Figueiredo, Jose Luiz; Lee, Haeshin; Kambhampati, Swetha; Lee, Timothy; Cho, Seung-Woo; Gorbatov, Rostic; Iwamoto, Yoshiko; Dang, Tram T.; Dutta, Partha; Yeon, Ju Hun; Cheng, Hao; Pritchard, Christopher D.; Vegas, Arturo J.; Siegel, Cory D.; MacDougall, Samantha; Okonkwo, Michael; Thai, Anh; Stone, James R.; Coury, Arthur J.; Weissleder, Ralph; Langer, Robert; Anderson, Daniel G.

    2012-01-01

    The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques. PMID:23236189

  3. Intravascular optical coherence tomography: differentiation of atherosclerotic plaques and quantification of vessel dimensions in crural arterial specimens

    International Nuclear Information System (INIS)

    Purpose: Intravascular optical coherence tomography (OCT) is a new technique based on infrared light that visualizes the arteries with a resolution of 10-20 μm. Intravascular ultrasound (IVUS) is the current in vivo reference standard and provides a resolution of 100-150 μm. This study compared OCT to IVUS and histopathology with respect to the ability to differentiate atherosclerotic plaques and quantify vascular dimensions in peripheral crural arteries ex vivo. Materials and Methods: 50 segments of atherosclerotic arteries derived from five amputated human lower extremities were examined. The different plaque types (fibrous, high-lipid content, calcified) were assigned by two independent examiners, and the sensitivity and specificity of OCT in comparison with histopathology as well as intra- and interobserver consensus were calculated. A comparison of OCT with IVUS addressed the parameters: luminal area (LA), vascular wall area (VA) and plaque area (PA). Results: When comparing OCT and histopathology with respect to the differentiation of various plaque types, sensitivities of 81% and specificities of 89% for fibrous plaques, of 100% and 93% for lipid-rich plaques and of 80% and 89% for calcified plaques were achieved (overall correlation 83%). Intra- and interobserver consensus was very high (κ=0.86 and κ=0.89, p2 accuracy ±1.8 mm2, r=0.95[p2 accuracy ±2.3 mm2, r=0.94[p2 accuracy ±2.3 mm2, r=0.80[p<0.01]). Conclusion: OCT allows the differentiation of atherosclerotic plaque types in crural arteries with high accuracy compared to histopathology. Quantitative measurements show a high correlation with IVUS, the current reference standard. (orig.)

  4. Detection of thrombosis and plaque rupture in atherosclerotic rabbit model by using 3.0 T MR imaging

    International Nuclear Information System (INIS)

    Objective: To explore the imaging of the thrombosis after pharmacological triggering of plaque rupture in atherosclerotic rabbit model by using 3.0 T high-resolution magnetic resonance imaging. Methods: Twenty male New Zealand white rabbits were divided into an experimental group (n=16) and a control group (n=4). The aortic wall injuries were induced by an intravascular balloon in experimental group rabbits after high cholesterol diet. The pharmacological triggering with Russell's viper venom and histamine was performed after 3 months of establishment of model. All of the animals underwent pre-trigger and post-trigger MR examinations including 3D time of fight (3D TOF), T1WI, T2WI and post contrast T1WI. Euthanasia was performed in all rabbits and gross anatomy and histological specimen of aorta were obtained. Comparing the location and length of the thrombus between MRI images and histopathology was used Pearson test. Comparing the calculated indexes of abdominal aorta between rabbits with and without thrombosis was used AVONA test and LSD-t test. Results: After triggering, 8 in 14 survived rabbits developed thrombosis in experimental group, meanwhile, no thrombus was found in control group. The accuracy of multi-sequences MRI for detecting of thrombus was 87.1% (27/31). MRI data correlated with the histopathology regarding thrombus length (r=0.85, P2 vs. (8.93±5.36) mm2, P<0.01]. Conclusion: MRI is useful tool to determine the thrombosis and plaque rupture in atherosclerotic rabbit model. (authors)

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

    Directory of Open Access Journals (Sweden)

    J.M. Aldrighi

    2005-05-01

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

  6. Identification of atherosclerotic plaque components using cluster analysis of multispectral MR images: comparison with histology

    Science.gov (United States)

    Clarke, Sharon; Rutt, Brian K.; Lucas, Alexandra; Lownie, Stephen P.; Hammond, Robert; Mitchell, Ross

    2000-04-01

    The composition of atherosclerotic lesions in the carotid arteries is believed to be an important predictor of stroke risk. Several MR contrasts may be necessary to discriminate between different plaque components, and multispectral analysis can used to integrate the information obtained from these multiple contrasts. This study presents the use of registered MR and histological images of carotid endarterectomy specimens as a tool for the quantitative assessment of maximum likelihood classification and other segmentation algorithms. Carotid endarterectomy specimens were imaged in a 1.5T GE Signa scanner. PD, T1, T2, diffusion spin echo weightings were obtained. MR images were registered with digitized images of the corresponding histology. A pathologist identified regions of collagen, calcification, cholesterol, hemorrhage on the histological images. Training and ground truth regions were selected. The accuracy of the maximum likelihood classification was assessed on a pixel by pixel basis using truth regions identified on histological images. The accuracy of multispectral analysis was calcification (73%), fibrin (68%), cholesterol (62%), fibrous plaque (53%). This technique was limited by registration inaccuracies caused by partial volume effects and histological artifacts. Despite these limitations, accuracy results were reasonable. This technique, with continued improvements, provides a framework for evaluating the accuracy of different segmentation algorithms.

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

    Directory of Open Access Journals (Sweden)

    Filippo Canducci

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

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

    Directory of Open Access Journals (Sweden)

    Chunmei Qi

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

  9. Relationship between changes in coronary atherosclerotic plaque burden measured by intravascular ultrasound and cardiovascular disease outcomes: a systematic literature review.

    Science.gov (United States)

    Forbes, Carol; Quek, Ruben G W; Deshpande, Sohan; Worthy, Gill; Ross, Janine; Kleijnen, Jos; Gandra, Shravanthi R; Kassahun, Helina; Wong, Nathan D; Nicholls, Stephen J

    2016-06-01

    Objective Evidence from coronary imaging studies suggests an association between increased atherosclerotic plaque burden and cardiovascular disease (CVD) outcomes. A systematic review was performed to evaluate the relationship between coronary atherosclerotic plaque burden changes measured by intravascular ultrasound (IVUS) and CVD outcomes. Research design and methods Rigorous systematic review methodology was used to identify prospective studies of any design assessing the relationship between atherosclerotic plaque volume (percentage or total atheroma volume [PAV or TAV]) changes and CVD outcomes, using multivariable analyses. Main outcome measures CVD outcomes including major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). Results Literature searches from inception to February 2015 retrieved 6958 records after de-duplication. From these four studies (14 papers) were included. One study reported a significantly lower rate of CVD outcomes associated with a greater reduction in PAV (hazard ratio [HR] 0.26, 95% confidence interval [CI] 0.07-0.83). One study reported that large plaque volume was significantly associated with a greater risk of major adverse cardiac events (MACEs) (HR 1.73, 95% CI: 1.02-2.96). Similarly, a third study reported a significant increase in MACE with an increase in baseline PAV (HR 1.51, 95% CI: 1.06-2.51). Only one potentially inadequately powered Japanese study did not find a statistically significant relationship between PAV changes and MACE. Conclusions The current evidence suggests an independent and statistically significant association between increases in coronary atherosclerotic plaque burden measured by IVUS and greater long-term risk of future CVD outcomes. However, this evidence comes from a limited number of studies which mainly focus on Japanese populations and populations after PCI. Further large prospective studies are required to confirm these findings. PMID:26949994

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  11. Adhesive strength of atherosclerotic plaque in a mouse model depends on local collagen content and elastin fragmentation.

    Science.gov (United States)

    Wang, Ying; Johnson, John A; Fulp, Abigail; Sutton, Michael A; Lessner, Susan M

    2013-02-22

    Atherosclerotic plaque rupture is a major cause of myocardial infarction and ischemic stroke. The adhesive strength of the bond between a plaque and the vascular wall, measured as local energy release rate, G, is used for quantitative plaque stability estimation. We tested the hypothesis that adhesive strength varies with plaque composition. Matrix metalloproteinase-12 (MMP12) deficiency was previously reported to alter lesion composition. To estimate G values, peeling experiments are performed on aortic plaques from apolipoprotein E knockout (apoE KO) and apoE MMP12 double knockout (DKO) male mice after 8 months on high-fat diet. For plaques in apoE KO and apoE MMP12 DKO mice, experimental values for G differ significantly (paveraging 19.2J/m(2) and 12.1J/m(2), respectively. Histology confirms that plaques delaminate along their interface with the underlying internal elastic lamina (IEL) in both genotypes. Quantitative image analysis of stained tissue sections demonstrates a significant positive correlation (p<0.05) between local collagen content of lesions and G values in both genotypes, indicating that adhesive strength of plaques depends on local collagen content. Surprisingly, macrophage content of aortic plaques is neither significantly correlated with G values nor significantly different between genotypes. The IEL underlying plaques in apoE KO mice is significantly more fragmented (number of breaks and length of breaks) than in apoE MMP12 DKO mice, suggesting that elastin fragmentation also influences adhesion strength of plaques. Overall, our results suggest that plaques adhere more strongly to the underlying IEL in apoE KO mice than in apoE MMP12 DKO mice. PMID:23261250

  12. Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors

    OpenAIRE

    Rozie, S.; de Weert, T. T.; de Monyé, C.; Homburg, P. J.; Tanghe, H L J; Dippel, D W J; van der Lugt, A.

    2009-01-01

    The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic a...

  13. Tiaozhi Tongmai Granules reduce atherogenesis and promote the expression of ATP-binding cassette transporter A1 in rabbit atherosclerotic plaque macrophages and the liver

    Directory of Open Access Journals (Sweden)

    Qing Sun

    2014-07-01

    Conclusions: Tiaozhi Tongmai Granules appear to have an anti-atherogenic effect that is most likely mediated by simultaneously upregulating the protein expression of ABCA1 in rabbit atherosclerotic plaque macrophages and in the liver.

  14. Cadmium exposure and atherosclerotic carotid plaques –Results from the Malmö diet and Cancer study

    Energy Technology Data Exchange (ETDEWEB)

    Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.se [Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg (Sweden); Barregard, Lars, E-mail: lars.barregard@amm.gu.se [Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE 413 45 Gothenburg (Sweden); Sallsten, Gerd, E-mail: gerd.sallsten@amm.gu.se [Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE 413 45 Gothenburg (Sweden); Forsgard, Niklas, E-mail: niklas.forsgard@vgregion.se [Department of Clinical Chemistry, Sahlgrenska University Hospital, SE-413 45 Gothenburg (Sweden); Östling, Gerd, E-mail: gerd.ostling@med.lu.se [Cardiovascular Epidemiology, Department of Clinical Sciences in Malmö, CRC, Jan Waldenströms gata 35, Skane University Hospital, Malmö, 205 02 Malmö (Sweden); Persson, Margaretha, E-mail: margaretha.persson@med.lu.se [Cardiovascular Epidemiology, Department of Clinical Sciences in Malmö, CRC, Jan Waldenströms gata 35, Skane University Hospital, Malmö, 205 02 Malmö (Sweden); Borné, Yan, E-mail: yan.borne@med.lu.se [Cardiovascular Epidemiology, Department of Clinical Sciences in Malmö, CRC, Jan Waldenströms gata 35, Skane University Hospital, Malmö, 205 02 Malmö (Sweden); and others

    2015-01-15

    Background: Epidemiological studies indicate that cadmium exposure through diet and smoking is associated with increased risk of cardiovascular disease. There are few data on the relationship between cadmium and plaques, the hallmark of underlying atherosclerotic disease. Objectives: To examine the association between exposure to cadmium and the prevalence and size of atherosclerotic plaques in the carotid artery. Methods: A population sample of 4639 Swedish middle-aged women and men was examined in 1991–1994. Carotid plaque was determined by B-mode ultrasound. Cadmium in blood was analyzed by inductively coupled plasma mass spectrometry. Results: Comparing quartile 4 with quartile 1 of blood cadmium, the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6–2.2) after adjustment for sex and, age; 1.4 (1.1–1.8) after additional adjustment for smoking status; 1.4 (1.1–1.7) after the addition of education level and life style factors; 1.3 (1.03–1.8) after additional adjustment for risk factors and predictors of cardiovascular disease. No effect modification by sex was found in the cadmium-related prevalence of plaques. Similarly, ORs for the prevalence of small and large plaques were after full adjustment 1.4 (1.0–2.1) and 1.4 (0.9–2.0), respectively. The subgroup of never smokers showed no association between cadmium and atherosclerotic plaques. Conclusions: These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans. The role of smoking remains unclear. It may both cause residual confounding and be a source of pro-atherogenic cadmium exposure. - Highlights: • Blood cadmium level is associated with atherosclerotic plaques in the carotid artery. • The results extend previous knowledge of cadmium exposure and clinical events. • The role of smoking remains unclear.

  15. Cadmium exposure and atherosclerotic carotid plaques –Results from the Malmö diet and Cancer study

    International Nuclear Information System (INIS)

    Background: Epidemiological studies indicate that cadmium exposure through diet and smoking is associated with increased risk of cardiovascular disease. There are few data on the relationship between cadmium and plaques, the hallmark of underlying atherosclerotic disease. Objectives: To examine the association between exposure to cadmium and the prevalence and size of atherosclerotic plaques in the carotid artery. Methods: A population sample of 4639 Swedish middle-aged women and men was examined in 1991–1994. Carotid plaque was determined by B-mode ultrasound. Cadmium in blood was analyzed by inductively coupled plasma mass spectrometry. Results: Comparing quartile 4 with quartile 1 of blood cadmium, the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6–2.2) after adjustment for sex and, age; 1.4 (1.1–1.8) after additional adjustment for smoking status; 1.4 (1.1–1.7) after the addition of education level and life style factors; 1.3 (1.03–1.8) after additional adjustment for risk factors and predictors of cardiovascular disease. No effect modification by sex was found in the cadmium-related prevalence of plaques. Similarly, ORs for the prevalence of small and large plaques were after full adjustment 1.4 (1.0–2.1) and 1.4 (0.9–2.0), respectively. The subgroup of never smokers showed no association between cadmium and atherosclerotic plaques. Conclusions: These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans. The role of smoking remains unclear. It may both cause residual confounding and be a source of pro-atherogenic cadmium exposure. - Highlights: • Blood cadmium level is associated with atherosclerotic plaques in the carotid artery. • The results extend previous knowledge of cadmium exposure and clinical events. • The role of smoking remains unclear

  16. Control study of MRI and histopathology in early atherosclerotic plaque of rabbits

    International Nuclear Information System (INIS)

    Objective: To explore the diagnostic value of MRI in the early atherosclerosis. Materials and Methods: Atherosclerosis was induced in 20 New Zealand White male rabbits with high cholesterol diet. Rabbits underwent serial MRI at 9 and 18 weeks after high cholesterol diet. Axial T1 and fat-suppressed PDWI spin echo images of the abdominal aorta were obtained above and below the right renal arteries. The signal intensity and morphologic features of plaque in the various phases after high cholesterol diet in MRI were analyzed and compared with those of histopathology. Results: Plaque could be observed in all animals on MRI at 9 weeks after high cholesterol diet, and mild enhancement of the plaque could be noted on enhanced imaging. Imaging effect was the best at T1 sequence. Plaque size increased gradually at 18 weeks. Plaque and vessel wall were all enrichment. In histopathology, foam cells, collagen and matrix fiber component can be seen in the various phases. Conclusion: The conventional MRI technique can be used to assess the formation and development of the early atherosclerosis dynamically and histologically. (authors)

  17. Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation

    International Nuclear Information System (INIS)

    Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of 18F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model. Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta. Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity. PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion

  18. Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques

    International Nuclear Information System (INIS)

    Genes induced or suppressed by oxidized low-density lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using the differential display reverse transcriptase polymerase chain reaction. One of the differentially expressed (up-regulated) cDNA fragments was found to contain sequences corresponding to monocyte chemotactic protein-3 (MCP-3). The stimulatory effect of the oxLDL on the expression of MCP-3 mRNA was both time- and dose-dependent. Treatment with GF109203X and genistein, inhibitors of protein kinase C and tyrosine kinase, respectively, had no effect on the induction of MCP-3 mRNA by oxLDL, while treatment with cycloheximide inhibited the induction. The induction was reproduced by the lipid components in oxLDL such as 9-HODE and 13-HODE, which are known to activate the peroxisome proliferator-activated receptor γ (PPARγ). Introduction of an endogenous PPARγ ligand, 15d-PGJ2, in the culture of THP-1 cells resulted in the induction of MCP-3 gene expression. Furthermore, analyses of human atherosclerotic plaques revealed that the expressional pattern of MCP-3 in the regions of neointimal and necrotic core overlapped with that of PPARγ. These results suggest that oxLDL delivers its signal for MCP-3 expression via PPARγ, which may be further related to the atherogenesis

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

    Directory of Open Access Journals (Sweden)

    Kim Taehong

    2007-03-01

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

  20. Carotid ultrasound symptomatology using atherosclerotic plaque characterization: a class of Atheromatic systems.

    Science.gov (United States)

    Acharya, U Rajendra; S, Vinitha Sree; Molinari, Filippo; Saba, Luca; Nicolaides, Andrew; Shafique, Shoaib; Suri, Jasjit S

    2012-01-01

    In this paper, we present a Computer Aided Diagnosis (CAD) based technique (Atheromatic system) for classification of carotid plaques in B-mode ultrasound images into symptomatic or asymptomatic classes. This system, called Atheromatic, has two steps: (i) feature extraction using a combination of Discrete Wavelet Transform (DWT) and averaging algorithms and (ii) classification using Support Vector Machine (SVM) classifier for automated decision making. The CAD system was built and tested using a database consisting of 150 asymptomatic and 196 symptomatic plaque regions of interests which were manually segmented. The ground truth of each plaque was determined based on the presence or absence of symptoms. Three-fold cross-validation protocol was adapted for developing and testing the classifiers. The SVM classifier with a polynomial kernel of order 2 recorded the highest classification accuracy of 83.7%. In the clinical scenario, such a technique, after much more validation, can be used as an adjunct tool to aid physicians by giving a second opinion on the nature of the plaque (symptomatic/asymptomatic) which would help in the more confident determination of the subsequent treatment regime for the patient. PMID:23366606

  1. Lipid volume fraction in atherosclerotic plaque phantoms classified under saline conditions by multispectral angioscopy at near-infrared wavelengths around 1200 nm.

    Science.gov (United States)

    Matsui, Daichi; Ishii, Katsunori; Awazu, Kunio

    2016-05-01

    To identify high-risk atherosclerotic lesions, we require detailed information on the stability of atherosclerotic plaques. In this study, we quantitatively classified the lipid volume fractions in atherosclerotic plaque phantoms by a novel angioscope combined with near-infrared multispectral imaging. The multispectral angioscope was operated at peak absorption wavelengths of lipid in vulnerable plaques (1150, 1200, and 1300 nm) and at lower absorption wavelengths of water. The potential of the multispectral angioscope was demonstrated in atherosclerotic plaque phantoms containing 10-60 vol.% lipid and immersed in saline solution. The acquired multispectral data were processed by a spectral angle mapper algorithm, which enhanced the simulated plaque areas. Consequently, we classified the lipid volume fractions into five categories (0-5, 5-15, 15-30, 30-50, and 50-60 vol.%). Multispectral angioscopy at wavelengths around 1200 nm is a powerful tool for quantitatively evaluating the stability of atherosclerotic plaques based on the lipid volume fractions. PMID:26861978

  2. Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors

    International Nuclear Information System (INIS)

    The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic artery. The contribution of different components was measured as the number of voxels within defined ranges of HU values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid artery. The severity of stenosis and PV were moderately correlated. Age and smoking were independently related to PV. Patients with hypercholesterolemia had significantly less lipid and more calcium in their plaques than patients without hypercholesterolemia. Other cardiovascular risk factors were not significantly related to PV or plaque composition. Luminal stenosis of the carotid artery partly reflects the amount of atherosclerotic carotid disease. Plaque volume and plaque composition are associated with cardiovascular risk factors. (orig.)

  3. Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Rozie, S.; Weert, T.T. de; Monye, C. de; Homburg, P.J.; Tanghe, H.L.J.; Lugt, A. van der [Erasmus MC, University Medical Center Rotterdam, Departments of Radiology, Rotterdam (Netherlands); Dippel, D.W.J. [Erasmus MC, University Medical Center Rotterdam, Department of Neurology, PO Box 2040, Rotterdam (Netherlands)

    2009-09-15

    The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic artery. The contribution of different components was measured as the number of voxels within defined ranges of HU values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid artery. The severity of stenosis and PV were moderately correlated. Age and smoking were independently related to PV. Patients with hypercholesterolemia had significantly less lipid and more calcium in their plaques than patients without hypercholesterolemia. Other cardiovascular risk factors were not significantly related to PV or plaque composition. Luminal stenosis of the carotid artery partly reflects the amount of atherosclerotic carotid disease. Plaque volume and plaque composition are associated with cardiovascular risk factors. (orig.)

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Hashimura, Keisuke; Ishii, Katsunori; Awazu, Kunio

    2015-11-01

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

  6. Comparison between MDCT and Grayscale IVUS in a Quantitative Analysis of Coronary Lumen in Segments with or without Atherosclerotic Plaques

    Energy Technology Data Exchange (ETDEWEB)

    Falcão, João L. A. A.; Falcão, Breno A. A. [Heart Institute (InCor), University of São Paulo Medical School (USP), São Paulo, SP (Brazil); Gurudevan, Swaminatha V. [Cedars-Sinai Heart Institute, Los Angeles, California, USA (United States); Campos, Carlos M.; Silva, Expedito R.; Kalil-Filho, Roberto; Rochitte, Carlos E.; Shiozaki, Afonso A.; Coelho-Filho, Otavio R.; Lemos, Pedro A. [Heart Institute (InCor), University of São Paulo Medical School (USP), São Paulo, SP (Brazil)

    2015-04-15

    The diagnostic accuracy of 64-slice MDCT in comparison with IVUS has been poorly described and is mainly restricted to reports analyzing segments with documented atherosclerotic plaques. We compared 64-slice multidetector computed tomography (MDCT) with gray scale intravascular ultrasound (IVUS) for the evaluation of coronary lumen dimensions in the context of a comprehensive analysis, including segments with absent or mild disease. The 64-slice MDCT was performed within 72 h before the IVUS imaging, which was obtained for at least one coronary, regardless of the presence of luminal stenosis at angiography. A total of 21 patients were included, with 70 imaged vessels (total length 114.6 ± 38.3 mm per patient). A coronary plaque was diagnosed in segments with plaque burden > 40%. At patient, vessel, and segment levels, average lumen area, minimal lumen area, and minimal lumen diameter were highly correlated between IVUS and 64-slice MDCT (p < 0.01). However, 64-slice MDCT tended to underestimate the lumen size with a relatively wide dispersion of the differences. The comparison between 64-slice MDCT and IVUS lumen measurements was not substantially affected by the presence or absence of an underlying plaque. In addition, 64-slice MDCT showed good global accuracy for the detection of IVUS parameters associated with flow-limiting lesions. In a comprehensive, multi-territory, and whole-artery analysis, the assessment of coronary lumen by 64-slice MDCT compared with coronary IVUS showed a good overall diagnostic ability, regardless of the presence or absence of underlying atherosclerotic plaques.

  7. Clinical feasibility of 3D automated coronary atherosclerotic plaque quantification algorithm on coronary computed tomography angiography: Comparison with intravascular ultrasound

    International Nuclear Information System (INIS)

    To evaluate the diagnostic performance of automated coronary atherosclerotic plaque quantification (QCT) by different users (expert/non-expert/automatic). One hundred fifty coronary artery segments from 142 patients who underwent coronary computed tomography angiography (CCTA) and intravascular ultrasound (IVUS) were analyzed. Minimal lumen area (MLA), maximal lumen area stenosis percentage (%AS), mean plaque burden percentage (%PB), and plaque volume were measured semi-automatically by expert, non-expert, and fully automatic QCT analyses, and then compared to IVUS. Between IVUS and expert QCT analysis, the correlation coefficients (r) for the MLA, %AS, %PB, and plaque volume were excellent: 0.89 (p < 0.001), 0.84 (p < 0.001), 0.91 (p < 0.001), and 0.94 (p < 0.001), respectively. There were no significant differences in the mean parameters (all p values >0.05) except %AS (p = 0.01). The automatic QCT analysis showed comparable performance to non-expert QCT analysis, showing correlation coefficients (r) of the MLA (0.80 vs. 0.82), %AS (0.82 vs. 0.80), %PB (0.84 vs. 0.73), and plaque volume (0.84 vs. 0.79) when they were compared to IVUS, respectively. Fully automatic QCT analysis showed clinical utility compared with IVUS, as well as a compelling performance when compared with semiautomatic analyses. (orig.)

  8. Clinical feasibility of 3D automated coronary atherosclerotic plaque quantification algorithm on coronary computed tomography angiography: Comparison with intravascular ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyung-Bok [Yonsei University Health System, Yonsei-Cedar Sinai Integrative Cardiovascular Imaging Research Center, Seoul (Korea, Republic of); Myongji Hospital, Division of Cardiology, Cardiovascular Center, Goyang (Korea, Republic of); Lee, Byoung Kwon [Yonsei University College of Medicine, Division of Cardiology, Gangnam Severance Hospital, Seoul (Korea, Republic of); Shin, Sanghoon [Yonsei University Health System, Yonsei-Cedar Sinai Integrative Cardiovascular Imaging Research Center, Seoul (Korea, Republic of); National Health Insurance Corporation Ilsan Hospital, Division of Cardiology, Goyang (Korea, Republic of); Heo, Ran; Chang, Hyuk-Jae; Chung, Namsik [Yonsei University Health System, Yonsei-Cedar Sinai Integrative Cardiovascular Imaging Research Center, Seoul (Korea, Republic of); Yonsei University Health System, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of); Arsanjani, Reza [Cedars-Sinai Medical Center, Departments of Imaging and Medicine, Cedars-Sinai Heart Institute, Los Angeles, CA (United States); Kitslaar, Pieter H. [Leiden University Medical Center, Department of Radiology, Division of Image Processing, Leiden (Netherlands); Medis medical Imaging Systems B.V., Leiden (Netherlands); Broersen, Alexander; Dijkstra, Jouke [Leiden University Medical Center, Department of Radiology, Division of Image Processing, Leiden (Netherlands); Ahn, Sung Gyun [Yonsei University Wonju Severance Christian Hospital, Division of Cardiology, Wonju (Korea, Republic of); Min, James K. [New York-Presbyterian Hospital, Institute for Cardiovascular Imaging, Weill-Cornell Medical College, New York, NY (United States); Hong, Myeong-Ki; Jang, Yangsoo [Yonsei University Health System, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of)

    2015-10-15

    To evaluate the diagnostic performance of automated coronary atherosclerotic plaque quantification (QCT) by different users (expert/non-expert/automatic). One hundred fifty coronary artery segments from 142 patients who underwent coronary computed tomography angiography (CCTA) and intravascular ultrasound (IVUS) were analyzed. Minimal lumen area (MLA), maximal lumen area stenosis percentage (%AS), mean plaque burden percentage (%PB), and plaque volume were measured semi-automatically by expert, non-expert, and fully automatic QCT analyses, and then compared to IVUS. Between IVUS and expert QCT analysis, the correlation coefficients (r) for the MLA, %AS, %PB, and plaque volume were excellent: 0.89 (p < 0.001), 0.84 (p < 0.001), 0.91 (p < 0.001), and 0.94 (p < 0.001), respectively. There were no significant differences in the mean parameters (all p values >0.05) except %AS (p = 0.01). The automatic QCT analysis showed comparable performance to non-expert QCT analysis, showing correlation coefficients (r) of the MLA (0.80 vs. 0.82), %AS (0.82 vs. 0.80), %PB (0.84 vs. 0.73), and plaque volume (0.84 vs. 0.79) when they were compared to IVUS, respectively. Fully automatic QCT analysis showed clinical utility compared with IVUS, as well as a compelling performance when compared with semiautomatic analyses. (orig.)

  9. Attenuation-based characterization of coronary atherosclerotic plaque: Comparison of dual source and dual energy CT with single-source CT and histopathology

    International Nuclear Information System (INIS)

    Objective: To compare different CT acquisition techniques regarding for attenuation-based characterization of coronary atherosclerotic plaques using histopathology as the standard of reference. Materials and methods: In a post mortem study 17 human hearts were studied with dual-source CT (DSCT) and dual energy CT (DECT) mode on a DSCT as well as with 16-slice single-source CT (SSCT). At autopsy, atherosclerotic lesions were cut at 5 μm sections. Histopathologic classification of the plaques according to the American Heart Association (AHA) criteria was performed by two pathologists. Attenuation values of all plaques were measured in DSCT, DECT and SSCT studies, respectively and classified based on attenuation according to modified AHA criteria. Results: 58 coronary plaques were identified at autopsy. Regardless of the CT technique only 52/58 plaques were found at CT (sensitivity = 89.6%). There was no significant difference between the mean attenuation values of different plaque types between DSCT, DECT, and SSCT: type IV: 11 HU/8 HU/19 HU; type Va: 44 HU/45 HU/52 HU; type Vb: 1088 HU/966 HU/1079 HU). The sensitivity for correct classification varied depending on the plaque type (type II = 0%, type III = 0%, type IV = 43%, type Va = 58%, Vb = 97%). Conclusion: Independent of the used acquisition technique, SSCT, DSCT and DECT show similar results for attenuation-based characterization of atherosclerotic coronary plaques.

  10. Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque

    DEFF Research Database (Denmark)

    Fu, S; Davies, Michael Jonathan; Stocker, R;

    1998-01-01

    Oxidative damage might be important in atherogenesis. Oxidized lipids are present at significant concentrations in advanced human plaque, although tissue antioxidants are mostly present at normal concentrations. Indirect evidence of protein modification (notably derivatization of lysine) or...... close similarities in relative abundances in the latter two circumstances indicate that hydroxyl radical damage might occur in plaque. The relatively higher level of dityrosine in plaque than that observed after radiolysis suggests the additional involvement of HOCl-mediated reactions in advanced plaque....

  11. The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine

    Directory of Open Access Journals (Sweden)

    Saskia J. H. Brinkmann

    2015-05-01

    Full Text Available Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS and thereby nitric oxide (NO, respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9, standard rabbit chow plus atorvastatin (group S, n = 8, standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8 or standard rabbit chow (group C, n = 9 as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.

  12. Data on the lipoprotein (a), coronary atherosclerotic burden and vulnerable plaque phenotype in angiographic obstructive coronary artery disease.

    Science.gov (United States)

    Niccoli, Giampaolo; Chin, Diana; Scalone, Giancarla; Panebianco, Mario; Abbolito, Sofia; Cosentino, Nicola; Jacoangeli, Francesca; Refaat, Hesham; Gallo, Giovanna; Salerno, Gerardo; Volpe, Massimo; Crea, Filippo; De Biase, Luciano

    2016-06-01

    Lipoprotein Lp(a) represents an independent risk factor for coronary artery disease (CAD). However, its association with CAD burden and lipid rich plaques prone to rupture in patients with acute coronary syndrome (ACS) still remains unknown. These data aim to investigate the association among serum Lipoprotein(a) (Lpa) levels, coronary atherosclerotic burden and features of culprit plaque in patients with ACS and obstructive CAD. For his reason, a total of 500 ACS patients were enrolled for the angiographic cohort and 51 ACS patients were enrolled for the optical coherence tomography (OCT) cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index, whereas OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. In the angiographic cohort, Lp(a) was a weak independent predictor of Sullivan score (p30 md/dl) compared to patients with lower Lp(a) levels (<30 md/dl) exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (P=0.02), a wider lipid arc (p=0.003) and a higher prevalence of thin-cap fibroatheroma (p=0.004). PMID:27158659

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

    Science.gov (United States)

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

    2012-01-01

    Hyperlipidemia is the cause of many complications in the human societies. In this study, the effect of methanol extracts of Quercus infectoria (QI) galls and Rosa damascena (RD) Mill flower were studied on lipid profile and atherosclerotic plaques formation in hyperlipidemic rabbits. Thirty-six New Zeland white rabbits randomly divided into 6 groups as control (I), hyperlipidemic (II), hyperlipidemic+QI (III), hyperlipidemic+RD (IV), +Atorvastolin (V) and hyperlipidemic+Orlistat (VI) and were fed with high fat diet (0.5% cholesterol and 16% hydrogenated vegetable oil) for 45 days. At the end of the study period, lipid profile and plaque formation were assessed. Total Cholesterol (TC), Low Density Lipoprotein (LDL) and Triglyceride (TG) levels were significantly increased in hyperlipidemic group compared with control group (p Quercus infectoria significantly decreased plasma levels of TC, TG and LDL (p < 0.001). It also decreased plaques formation in semi lunar valve and thoracic aorta. Rosa damascena mill flower methanol extract moderately decreased the levels of TC, TG, LDL and plaques formation but it was not significant. HDL levels and weight of animals did not show significant difference among groups. Based on the doses used in this study, our finding indicated that QI but no RD methanol extract has anti atherogenic and hypolipidemic activities. PMID:22530439

  14. Ultrasonic echolucent carotid plaques predict future strokes

    DEFF Research Database (Denmark)

    Grønholdt, Marie-Louise; Nordestgaard, B G; Schroeder, T V; Vorstrup, S; Sillesen, H

    2001-01-01

    We tested prospectively the hypothesis that stroke development can be predicted by echolucency of carotid atherosclerotic plaques in previously symptomatic and asymptomatic patients.......We tested prospectively the hypothesis that stroke development can be predicted by echolucency of carotid atherosclerotic plaques in previously symptomatic and asymptomatic patients....

  15. Characterising human atherosclerotic carotid plaque tissue composition and morphology using combined spectroscopic and imaging modalities.

    Science.gov (United States)

    Barrett, Hilary E; Mulvihill, John J; Cunnane, Eoghan M; Walsh, Michael T

    2015-01-01

    Calcification is a marked pathological component in carotid artery plaque. Studies have suggested that calcification may induce regions of high stress concentrations therefore increasing the potential for rupture. However, the mechanical behaviour of the plaque under the influence of calcification is not fully understood. A method of accurately characterising the calcification coupled with the associated mechanical plaque properties is needed to better understand the impact of calcification on the mechanical behaviour of the plaque during minimally invasive treatments. This study proposes a comparison of biochemical and structural characterisation methods of the calcification in carotid plaque specimens to identify plaque mechanical behaviour. Biochemical analysis, by Fourier Transform Infrared (FTIR) spectroscopy, was used to identify the key components, including calcification, in each plaque sample. However, FTIR has a finite penetration depth which may limit the accuracy of the calcification measurement. Therefore, this FTIR analysis was coupled with the identification of the calcification inclusions located internally in the plaque specimen using micro x-ray computed tomography (μX-CT) which measures the calcification volume fraction (CVF) to total tissue content. The tissue characterisation processes were then applied to the mechanical material plaque properties acquired from experimental circumferential loading of human carotid plaque specimen for comparison of the methods. FTIR characterised the degree of plaque progression by identifying the functional groups associated with lipid, collagen and calcification in each specimen. This identified a negative relationship between stiffness and 'lipid to collagen' and 'calcification to collagen' ratios. However, μX-CT results suggest that CVF measurements relate to overall mechanical stiffness, while peak circumferential strength values may be dependent on specific calcification geometries. This study

  16. Characterising human atherosclerotic carotid plaque tissue composition and morphology using combined spectroscopic and imaging modalities

    OpenAIRE

    Barrett, Hilary E; Mulvihill, John J.; Cunnane, Eoghan M; Walsh, Michael T

    2015-01-01

    Calcification is a marked pathological component in carotid artery plaque. Studies have suggested that calcification may induce regions of high stress concentrations therefore increasing the potential for rupture. However, the mechanical behaviour of the plaque under the influence of calcification is not fully understood. A method of accurately characterising the calcification coupled with the associated mechanical plaque properties is needed to better understand the impact of ...

  17. In-vivo quantitative T2 mapping of carotid arteries in atherosclerotic patients: segmentation and T2 measurement of plaque components

    OpenAIRE

    Biasiolli, Luca; Lindsay, Alistair C.; Chai, Joshua T.; Choudhury, Robin P.; Robson, Matthew D

    2013-01-01

    Background Atherosclerotic plaques in carotid arteries can be characterized in-vivo by multicontrast cardiovascular magnetic resonance (CMR), which has been thoroughly validated with histology. However, the non-quantitative nature of multicontrast CMR and the need for extensive post-acquisition interpretation limit the widespread clinical application of in-vivo CMR plaque characterization. Quantitative T2 mapping is a promising alternative since it can provide absolute physical measurements o...

  18. The relationship of the gene polymorphisms of matrix metalloproteinase-1, -2, -3 and -9 to the progression of coronary atherosclerotic plaque

    International Nuclear Information System (INIS)

    Objective: To evaluate the influence of the gene polymorphisms of matrix metalloproteinase(mmp)-1, -2, -3 and -9 on coronary atherosclerotic plaque progression. Methods: During the period of January 2005-December 2008, 80 patients with coronary heart disease underwent two times coronary angiography at authors' hospital. Based on the angiographic findings, the patients were classified into plaque progression group (n = 31) and plaque non-progression group (n = 49). Coronary atherosclerotic plaque progression was arbitrarily defined as that the minimal lumen diameter (MLD) of coronary artery showed a decrease ≥ 0.4 mm on the second coronary angiography. The detailed history and clinical examination results were collected, including serum concentrations of lipid profiling, fasting glucose and hs-CRP. Genotypings for polymorphic variances of MMP-1 (-1607 G / GG), MMP-2 (-955 A / C), MMP-3 (-1612 5A / 6A ) and MMP-9 (-1562 C/T) were performed by polymerase chain reaction (PCR) and sequencing analysis in two groups. Comparison of the clinical characteristics and polymorphisms between two groups was made to assess their effects on coronary atherosclerotic plaque progression. Results: More female patients and patients with acute coronary syndrome (ACS) were noted in patients with plaque progression compare to those with no progression (41.9% vs. 18.4%, P < 0.05 and 77.4% vs. 46.3%, P < 0.01, respectively). The serum hs-CRP level also significantly increased in group with plaque progression (0.26 ± 0.44 mg / L vs. 0.02 ± 0.14 mg / L, P < 0.01). Multivariable logistic regression analysis revealed that serum hs-CRP concentration and ACS were independent risk factors of coronary atherosclerotic plaque progression (OR: 12.63,95% CI:1.45-110.29, P < 0.05 and OR:2.99,95% CI:1.04-8.63, P < 0.05, respectively). The frequencies of 6A / 6A genotype and 6A allele of MMP-3 promoter at location -1612 were significantly higher in group with plaque progression than that in group with

  19. Chlamydia pneumoniae in atherosclerotic carotid artery plaques: high prevalence among heavy smokers.

    Science.gov (United States)

    Dobrilovic, N; Vadlamani, L; Meyer, M; Wright, C B

    2001-06-01

    This study was designed to determine the prevalence of Chlamydia pneumoniae in carotid artery plaques. Although there have been numerous studies evaluating coronary plaques for this bacterium fewer studies have assessed noncoronary vasculature. In addition we wished to evaluate whether correlation exists between the presence of C. pneumoniae in carotid plaques and established risk factors for atherosclerosis. Sixty intact carotid artery plaques removed during surgery (carotid endarterectomy) were formalin-fixed and paraffin-embedded according to conventional techniques. These samples were evaluated by polymerase chain reaction analysis to detect presence of C. pneumoniae DNA. Results were tabulated and compared against established risk factors for atherosclerosis: diabetes, hypertension, hyperlipidemia, age, and smoking. Forty-two (70.0%) of the 60 plaques that were evaluated tested positive for the presence of C. pneumoniae DNA by polymerase chain reaction analysis. In the sample defined as being from heavy smokers (greater than 15-pack-year history) 33 (94.3%) of 35 plaques tested positive whereas two (5.7%) tested negative. This correlation demonstrated statistical significance (P = 1.36 x 10(-6), two-tailed Fisher exact test). Presence of C. pneumoniae in carotid plaques demonstrated no statistically significant correlation with diabetes, hypertension, or hyperlipidemia. Age as a risk factor was examined but not statistically evaluated because of the narrow range within our patient sample. Analysis of the data reveals that C. pneumoniae is present in large numbers of atheromatous plaques as is consistent with emerging data. What is interesting though is that 33 (94.3%) of the 35 smokers had plaques that tested positive for the bacterium as opposed to only nine (36.0%) of the 25 nonsmokers. Identification of specific populations exhibiting a high prevalence of C. pneumoniae may serve to focus future studies. Ongoing investigation will seek to determine whether C

  20. Repeatability of in vivo quantification of atherosclerotic carotid artery plaque components by supervised multispectral classification

    OpenAIRE

    Gao, Shan; van ’t Klooster, Ronald; van Wijk, Diederik F.; Nederveen, Aart J.; Lelieveldt, Boudewijn P.F.; van der Geest, Rob J.

    2015-01-01

    Objective To evaluate the agreement and scan–rescan repeatability of automated and manual plaque segmentation for the quantification of in vivo carotid artery plaque components from multi-contrast MRI. Materials and methods Twenty-three patients with 30–70 % stenosis underwent two 3T MR carotid vessel wall exams within a 1 month interval. T1w, T2w, PDw and TOF images were acquired around the region of maximum vessel narrowing. Manual delineation of the vessel wall and plaque components (lipid...

  1. TU-F-12A-06: BEST IN PHYSICS (IMAGING) - A Novel Catheter-Based Radionuclide Imaging System to Characterize Atherosclerotic Plaque

    Energy Technology Data Exchange (ETDEWEB)

    Zaman, R; Kosuge, H; Carpenter, C; Pratx, G; Sun, C; McConnell, M; Xing, L [Stanford University School of Medicine, Stanford, CA (United States)

    2014-06-15

    Purpose: Atherosclerosis underlies coronary artery diseases, the leading cause of death in the United States and worldwide. In this study, we developed a novel catheter-based radionuclide imaging (CRI) system to image 18F-fluorodeoxyglucose (18F-FDG), a radionuclide, a marker of vascular inflammation, in murine carotid arteries and characterized the system for spatial resolution from multiple scintillating materials. Methods: The catheter system includes 35 mm and 8 mm fixed focal length lenses, which are subsequently connected to a CMOS camera and fiber holder. The distal ferrule of an image bundle is terminated with a wide-angle lens. The novelty of this system is a scintillating balloon with a crystal tip in the front of the wide angle lens to image light from the decay of 18F-FDG emission signal. The scintillating balloon is fabricated from 1mL of silicone RTV catalyst mixed with 1 mL base and 50 mg/mL calcium fluoride doped with Europium (CaF2:Eu). To identify the optimal scintillating materials with respect to resolution, we calculated modulation transfer function (MTF) of Yttrium Aluminum Garnet doped with Cerium (YAG:Ce), anthracene, and CaF2:Eu phosphors using a thin line optical phantom (Fig. 1a-1b). Macrophage-rich FVB murine atherosclerotic carotid plaque model (n = 4) was used in ex vivo experiments. Confirmatory imaging was also performed by an external optical imaging system (IVIS-200). Results: Analysis of the different phosphors (Fig 1b) showed that CaF2:Eu enabled the best resolution of 1.2μm. The CRI system visualized 18F-FDG in atherosclerotic plaques (Fig. 1d). The ligated left carotid (LR) artery exhibited 4× higher 18F-FDG signal intensity compared to the non-ligated right carotid (negative control) artery (1.65×10{sup 2} ±4.07×10{sup 1} vs. 4.44×10{sup 1}±2.17×10{sup 0}, A.U., p = 0.005) and confirmed with IVIS-200 (Fig. 1d). Conclusion: This CRI system enables high-resolution and sensitive detection of 18F-FDG uptake by murine

  2. Impaired gait pattern as a sensitive tool to assess hypoxic brain damage in a novel mouse model of atherosclerotic plaque rupture

    NARCIS (Netherlands)

    Roth, Lynn; Van Dam, Debby; Van der Donckt, Carole; Schrijvers, Dorien M.; Lemmens, Katrien; Van Brussel, Ilse; De Deyn, Peter P.; Martinet, Wim; De Meyer, Guido R. Y.

    2015-01-01

    Apolipoprotein E deficient (ApoE(-/-)) mice with abeterozygous mutation in the flbrillin-1 gene (Fbn1(C1039G+/-) show spontaneous atherosclerotic plaque ruptures, disturbances in cerebral flow and sudden death when fed a Western-type diet (WD). The present study focused on motor coordination and spa

  3. [Mycoplasma pneumoniae and Chlamydia pneumoniae are associated to inflammation and rupture of the atherosclerotic coronary plaques].

    Science.gov (United States)

    Ramires, José Antonio F; Higuchi, Maria de Lourdes

    2002-01-01

    In this review we report recent findings of our lab showing that Mycoplasma pneumoniae and Chlamydia pneumoniae are present in higher amount, associated with adventitial inflammation and positive vessel remodeling, in thrombosed coronary artery segments (CAS) of patients who died due to acute myocardial infarction. CD8T cell was the predominant lymphocytes in the plaque and CD24(B) cell in the adventitia. The mean numbers of lymphocytes were significantly higher in adventitia than in the plaque. Vulnerable plaques were usually associated with focal positive vessel remodeling and large lipidic atheromas. Mycoplasma is the only bacterium that needs cholesterol for proliferation. We hypothesized that the association of Mycoplasma pneumoniae and Chlamydia pneumoniae increases virulence of both bacteria, inducing inflammation and rupture of the plaque. The search of CMV and Helicobacter pylori resulted negative. PMID:15626350

  4. Carotid and femoral atherosclerotic plaques show different morphology. : Patterns of Peripheral Arterial Disease

    OpenAIRE

    Herisson, Fanny; Heymann, Marie-Françoise; Chétiveaux, Maud; Charrier, Céline; Battaglia, Séverine; Pilet, Paul; Rouillon, Thierry; Krempf, Michel; Lemarchand, Patricia; Heymann, Dominique; Gouëffic, Yann

    2011-01-01

    OBJECTIVE: Results of endovascular repair vary according to the arterial bed. We hypothesized that these differences may be related to the plaque features. To explore this hypothesis, we designed a prospective study that compared carotid and femoral atheroma. METHODS AND RESULTS: Patients that underwent femoral or carotid endarterectomy were included in our study. Demographic data and blood sampling were obtained prior to surgery. Plaques were evaluated for AHA grading, calcification and lipi...

  5. Association between albuminuria, atherosclerotic plaques, elevated pulse wave velocity, age, risk category and prognosis in apparently healthy individuals

    DEFF Research Database (Denmark)

    Greve, Sara V; Blicher, Marie K; Blyme, Adam;

    2014-01-01

    , with moderate SCORE or with high-intermediate or high FRS (all P hazard ratio 2.7 (1.6-4.8)] and 61...... years [hazard ratio 2.7 (1.5-4.7)], moderate [hazard ratio 2.4 (1.6-3.7)] or high SCORE risk group [hazard ratio 2.3 (1.2-4.7)] and low-intermediate [hazard ratio 3.3 (1.5-7.0)], high-intermediate [hazard ratio 2.3 (1.5-3.5)] and high FRS risk group [hazard ratio 2.0 (1.4-3.0)]. CONCLUSION: SVD...... atherosclerotic plaques or albuminuria defined as urine albumin/creatinine ratio at least 90th percentile of 0.73/1.06 mg/mmol men/women. In 2006, the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for ischemic heart disease was recorded (n...

  6. 99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques

    International Nuclear Information System (INIS)

    Several histopathological studies have demonstrated that vulnerable plaques are enriched in inflammatory cells. The aims of this study were: (1a) to test the ability of 99mTc-labelled interleukin-2 (99mTc-IL2) to bind to IL2R-positive (IL2R+) cells in carotid plaques and (1b) to correlate the plaque uptake of 99mTc-IL2, measured in vivo, with the number of IL2R+ cells within the plaque, measured ex vivo by histology (transversal study, TS), and (2) to evaluate changes in 99mTc-IL2 uptake in plaques, before and after treatment with a statin or a hypocholesterolaemic diet (longitudinal study, LS). Ultrasound scan was performed for plaque characterisation and localisation. Fourteen patients (16 plaques) eligible for endoarterectomy were recruited for the TS and underwent 99mTc-IL2 scintigraphy before surgery. Nine patients (13 plaques) were recruited for the LS; these patients received atorvastatin or a standard hypocholesterolaemic diet and 99mTc-IL2 scintigraphy was performed before and after 3 months of treatment. The degree of 99mTc-IL2 uptake was expressed as the plaque/background (T/B) ratio. In patients from TS, T/B ratios correlated with the percentage of IL2R+ cells at histology (r=0.707; p=0.002) and the number of IL2R+ cells at flow cytometry (r=0.711; p=0.006). No correlations were observed between ultrasound scores and either scintigraphic or histological findings. In patients from the LS, the mean 99mTc-IL2 uptake decreased in statin-treated patients (1.75±0.50 vs 2.16±0.44; p=0.012), while it was unchanged in the patients on the hypocholesterolaemic diet (2.33±0.45 vs 2.34±0.5). 99mTc-IL2 accumulates in vulnerable carotid plaques; this accumulation is correlated with the amount of IL2R+ cells and is influenced by lipid-lowering treatment with a statin. (orig.)

  7. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque

    Science.gov (United States)

    Fan, Yue-Mei; Hernesniemi, Jussi; Oksala, Niku; Levula, Mari; Raitoharju, Emma; Collings, Auni; Hutri-Kähönen, Nina; Juonala, Markus; Marniemi, Jukka; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Mennander, Ari; Tarkka, Matti; Kangas, Antti J.; Soininen, Pasi; Salenius, Juha Pekka; Klopp, Norman; Illig, Thomas; Laitinen, Tomi; Ala-Korpela, Mika; Laaksonen, Reijo; Viikari, Jorma; Kähönen, Mika; Raitakari, Olli T.; Lehtimäki, Terho

    2014-01-01

    Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT < CT < CC and rs1556259 AA < AG < GG as well as according to USF1 H3 (GCCCGG) copy number 0 < 1 < 2. Furthermore, the carriers of minor alleles of rs2516839 (C) and rs1556259 (G) of USF1 gene had decreased USF1 expression in atherosclerotic plaques (P = 0.028 and 0.08, respectively) as compared to non-carriers. The genetic variation in USF1 influence USF1 transcript expression in advanced atherosclerosis and regulates levels and metabolism of circulating apoB and apoB-containing lipoprotein particles in sex-dependent manner, but is not a major determinant of early markers of atherosclerosis. PMID:24722012

  8. The influence of inaccuracies in carotid MRI segmentation on atherosclerotic plaque stress computations.

    Science.gov (United States)

    Nieuwstadt, Harm A; Speelman, Lambert; Breeuwer, Marcel; van der Lugt, Aad; van der Steen, Anton F W; Wentzel, Jolanda J; Gijsen, Frank J H

    2014-02-01

    Biomechanical finite element analysis (FEA) based on in vivo carotid magnetic resonance imaging (MRI) can be used to assess carotid plaque vulnerability noninvasively by computing peak cap stress. However, the accuracy of MRI plaque segmentation and the influence this has on FEA has remained unreported due to the lack of a reliable submillimeter ground truth. In this study, we quantify this influence using novel numerical simulations of carotid MRI. Histological sections from carotid plaques from 12 patients were used to create 33 ground truth plaque models. These models were subjected to numerical computer simulations of a currently used clinically applied 3.0 T T1-weighted black-blood carotid MRI protocol (in-plane acquisition voxel size of 0.62 × 0.62 mm2) to generate simulated in vivo MR images from a known underlying ground truth. The simulated images were manually segmented by three MRI readers. FEA models based on the MRI segmentations were compared with the FEA models based on the ground truth. MRI-based FEA model peak cap stress was consistently underestimated, but still correlated (R) moderately with the ground truth stress: R = 0.71, R = 0.47, and R = 0.76 for the three MRI readers respectively (p carotid plaques with thin caps, the current clinically used in-plane acquisition voxel size (∼0.6 mm) is inadequate. FEA plaque stress computations would be considerably more reliable if they would be used to identify thick-cap carotid plaques with low stresses instead. PMID:24317274

  9. Cardiovascular magnetic resonance parameters of atherosclerotic plaque burden improve discrimination of prior major adverse cardiovascular events

    Directory of Open Access Journals (Sweden)

    Bansilal Sameer

    2009-04-01

    Full Text Available Abstract Aims Patients with prior major cardiovascular or cerebrovascular events (MACE are more likely to have future recurrent events independent of traditional cardiovascular disease risk factors. The purpose of this study was to determine if patients with traditional risk factors and prior MACE had increased cardiovascular magnetic resonance (CMR plaque burden measures compared to patients with risk factors but no prior events. Methods and Results Black blood carotid and thoracic aorta images were obtained from 195 patients using a rapid extended coverage turbo spin echo sequence. CMR measures of plaque burden were obtained by tracing lumen and outer vessel wall contours. Patients with prior MACE had significantly higher MR plaque burden (wall thickness, wall area and normalized wall index in carotids and thoracic aorta compared to those without prior MACE (Wall thickness carotids: 1.03 ± 0.03 vs. 0.93± 0.03, p = 0.001; SD wall thickness carotids: 0.137 ± 0.0008 vs. 0.102 ± 0.0004, p Conclusion A greater plaque burden and plaque eccentricity is prevalent among patients with prior MACE.

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

    OpenAIRE

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

    2012-01-01

    Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significant...

  11. Quantification of [18F]-FDG uptake in atherosclerotic plaque. Impact of renal function

    International Nuclear Information System (INIS)

    Impaired renal function causes both increased and prolonged tracer availability in the blood-pool which might result in increased tracer accumulation in atherosclerotic lesions. Therefore, the aim of this study was to investigate a possible correlation between the intensity of tracer uptake in atherosclerotic lesions and renal function. Data from 50 [18F]-fluoro-2-deoxy-D-glucose (FDG) scans were visually evaluated for tracer uptake in vessel wall alterations. Lesions were analyzed semiquantitatively by determining the blood-pool standardized uptake values (SUVblood-pools), maximum SUVs (SUVmaxs), and the target-to-background ratio (TBR). These parameters were tested for correlation with estimated glomerular filtration rate (eGFR), and cardiovascular risk factors. Both SUVblood-pools (rs=-0.32, p=0.03) and SUVmaxs for [18F]-FDG (rs=-0.50, p18F]-FDG demonstrated a significant positive correlation with eGFRs (rs=0.21, p=0.02). This study found that both intravascular tracer availability (SUVblood-pool) and intralesional tracer uptake (SUVmax) are influenced by renal function. Calculation of TBR to account for that effect may result in overcorrection in case of [18F]-FDG. Renal insufficiency or subclinical changes in renal function have to be considered as a confounding factor in PET of atherosclerotic lesions. (author)

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

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Jespersen, Søren Kragh; Hansen, J. U.; Nyssen, N.I.H.

    1998-01-01

    ) volts was calculated for the plaque region in each image. The standard deviation over the 48 MAL values were for each of the 7 angles between 0.12 V and 0.18 V. For each scan plane, the standard deviation was also calculated over the 7 images. The mean and standard deviation of these 48 numbers were 0...

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

    OpenAIRE

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

    2010-01-01

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

  14. Nuclear medicine and coronary artery disease: evaluation of tracers of myocardial perfusion and vulnerable atherosclerotic plaque; Medecine nucleaire et maladie coronarienne: evaluation de traceurs de la perfusion myocardique et de la plaque d'atherome vulnerable

    Energy Technology Data Exchange (ETDEWEB)

    Broisat, A

    2005-04-15

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

  15. Development and validation of an enzyme-linked immunosorbent assay for the quantification of a specific MMP-9 mediated degradation fragment of type III collagen--A novel biomarker of atherosclerotic plaque remodeling

    DEFF Research Database (Denmark)

    Barascuk, Natasha; Vassiliadis, Efstathios; Larsen, Lise;

    2011-01-01

    Degradation of collagen in the arterial wall by matrix metalloproteinases is the hallmark of atherosclerosis. We have developed an ELISA for the quantification of type III collagen degradation mediated by MMP-9 in urine....

  16. Correction of lumen contrast-enhancement influence on non-calcified coronary atherosclerotic plaque quantification on CT.

    Science.gov (United States)

    Kristanto, Wisnumurti; Tuncay, Volkan; Vliegenthart, Rozemarijn; van Ooijen, Peter M A; Oudkerk, Matthijs

    2015-02-01

    Lumen contrast-enhancement influences non-calcified atherosclerotic plaque Hounsfield-unit (HU) values in computed tomography (CT). This study aimed to construct and validate an algorithm to correct for this influence. Three coronary vessel phantoms with 1, 2, and 4 mm circular hollow lumina; with normal and plaque-infested walls were scanned simultaneously in oil using a dual-source CT scanner. Scanning was repeated as the lumina were alternately filled with water and four contrast solutions (100-400 HU, at 100 HU intervals). Images were reconstructed at 0.4 mm x-y pixel size. Pixel-by-pixel comparisons of contrast-enhanced and non-contrast-enhanced images confirmed exponential declining patterns in lumen contrast-enhancement influence on wall HU-values from the lumen border (y = Ae(-λx) + c). The median difference of the inside and outside 2-pixel radius part of the contrast-enhanced coronary phantom wall to the reference (non-contrast-enhanced images) was 45 and 2 HU, respectively. Based on the lumen contrast-enhancement influence patterns, a generalized correction algorithm was formulated. Application of the generalized correction algorithm to the inside 2-pixel radius part of the wall reduced the median difference to the reference to 4 HU. In conclusion, lumen contrast-enhancement influence on the vessel wall can be defined by an exponential approximation, allowing correction of the CT density of the vessel wall closest to the lumen. With this correction, a more accurate determination of vessel wall composition can be made. PMID:25326412

  17. Bacteria and bacterial DNA in atherosclerotic plaque and aneurysmal wall biopsies from patients with and without periodontitis

    Directory of Open Access Journals (Sweden)

    Zahra Armingohar

    2014-05-01

    Full Text Available Background: Several studies have reported an association between chronic periodontitis (CP and cardiovascular diseases. Detection of periodontopathogens, including red complex bacteria (RCB, in vascular lesions has suggested these bacteria to be involved in the pathogenesis of atherosclerosis and abdominal aortic aneurysms. Objective: In this study, we investigate bacteria and their DNA in vascular biopsies from patients with vascular diseases (VD; i.e. abdominal aortic aneurysms, atherosclerotic carotid, and common femoral arteries, with and without CP. Methods: DNA was extracted from vascular biopsies selected from 40 VD patients: 30 with CP and 10 without CP. The V3-V5 region of the 16S rDNA (V3-V5 was polymerase chain reaction (PCR-amplified, and the amplicons were cloned into Escherichia coli, sequenced, and classified (GenBank and the Human Oral Microbiome database. Species-specific primers were used for the detection of Porphyromonas gingivalis. In addition, 10 randomly selected vascular biopsies from the CP group were subjected to scanning electron microscopy (SEM for visualization of bacteria. Checkerboard DNA–DNA hybridization was performed to assess the presence of RCB in 10 randomly selected subgingival plaque samples from CP patients. Results: A higher load and mean diversity of bacteria were detected in vascular biopsies from VD patients with CP compared to those without CP. Enterobacteriaceae were frequently detected in vascular biopsies together with cultivable, commensal oral, and not-yet-cultured bacterial species. While 70% of the subgingival plaque samples from CP patients showed presence of RCB, only P. gingivalis was detected in one vascular biopsy. Bacterial cells were seen in all 10 vascular biopsies examined by SEM. Conclusions: A higher bacterial load and more diverse colonization were detected in VD lesions of CP patients as compared to patients without CP. This indicated that a multitude of bacterial species both

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

    Directory of Open Access Journals (Sweden)

    Dheeraj eKhurana

    2013-04-01

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

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

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    Ivanović Miloš

    2013-01-01

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

  20. HMGB1 is associated with atherosclerotic plaque composition and burden in patients with stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Martin Andrassy

    Full Text Available OBJECTIVES: The role of inflammation in atherosclerosis is widely appreciated. High mobility group box 1 (HMGB1, an injury-associated molecular pattern molecule acting as a mediator of inflammation, has recently been implicated in the development of atherosclerosis. In this study, we sought to investigate the association of plasma HMGB1 with coronary plaque composition in patients with suspected or known coronary artery disease (CAD. DESIGN: HMGB1, high sensitive troponin T (hsTnT and high sensitive C-reactive protein (hsCRP were determined in 152 consecutive patients with suspected or known stable CAD who underwent clinically indicated 256-slice coronary computed tomography angiography (CCTA. Using CCTA, we assessed 1 coronary calcification, 2 non-calcified plaque burden and 3 the presence of vascular remodeling in areas of non-calcified plaques. RESULTS: Using univariate analysis, hsCRP, hsTnT and HMGB1 as well as age, and atherogenic risk factors were associated with non-calcified plaque burden (r = 0.21, p = 0.009; r = 0.48, p<0.001 and r = 0.34, p<0.001, respectively. By multivariate analysis, hsTnT and HMGB1 remained independent predictors of the non-calcified plaque burden (r = 0.48, p<0.01 and r = 0.34, p<0.001, respectively, whereas a non-significant trend was noticed for hs-CRP (r = 0.21, p = 0.07. By combining hsTnT and HMGB1, a high positive predictive value for the presence of non-calcified and remodeled plaque (96% and 77%, respectively was noted in patients within the upper tertiles for both biomarkers, which surpassed the positive predictive value of each marker separately. CONCLUSIONS: In addition to hs-TnT, a well-established cardiovascular risk marker, HMGB1 is independently associated with non-calcified plaque burden in patients with stable CAD, while the predictive value of hs-CRP is lower. Complementary value was observed for hs-TnT and HMGB1 for the prediction of complex coronary plaque.

  1. Intraplaque hemorrhage is associated with higher structural stresses in human atherosclerotic plaques: an in vivo MRI-based 3d fluid-structure interaction study

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    Canton Gador

    2010-12-01

    Full Text Available Abstract Background Studies using medical images have shown that intraplaque hemorrhage may accelerate plaque progression and may produce a stimulus for atherosclerosis development by increasing lipid core and plaque volume and creating new destabilizing factors. Image-based 3D computational models with fluid-structure interactions (FSI will be used to perform plaque mechanical analysis and investigate possible associations between intraplaque hemorrhage and both plaque wall stress (PWS and flow shear stress (FSS. Methods In vivo MRI data of carotid plaques from 5 patients with intraplaque hemorrhage confirmed by histology were acquired. 3D multi-component FSI models were constructed for each plaque to obtain mechanical stresses. Plaque Wall Stress (PWS and Flow Shear Stress (FSS were extracted from all nodal points on the lumen surface of each plaque for analysis. Results The mean PWS value from all hemorrhage nodes of the 5 plaques combined was higher than that from non-hemorrhage nodes (75.6 versus 68.1 kPa, P = 0.0003. The mean PWS values from hemorrhage nodes for each of the 5 plaques were all significantly higher (5 out of 5 than those from non-hemorrhage nodes (P 2, P = 0.0002. However, the mean flow shear stress values from individual cases showed mixed results: only one out of five plaques showed mean FSS value from hemorrhage nodes was higher than that from non-hemorrhage nodes; three out of five plaques showed that their mean FSS values from hemorrhage nodes were lower than those from non-hemorrhage nodes; and one plaque showed that the difference had no statistical significance. Conclusion The results of this study suggested that intraplaque hemorrhage nodes were associated with higher plaque wall stresses. Compared to flow shear stress, plaque wall stress has a better correlation with plaque component feature (hemorrhage linked to plaque progression and vulnerability. With further validation, plaque stress analysis may provide

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

    OpenAIRE

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

    2015-01-01

    Background Despite systemic exposure to risk factors, the circulatory system develops varying patterns of atherosclerosis for unclear reasons. In a porcine model, we investigated the relationship between site‐specific lesion development and inflammatory pathways involved in the coronary arteries (CORs) and distal abdominal aortas (AAs). Methods and Results Diabetes mellitus (DM) and hypercholesterolemia (HC) were induced in 37 pigs with 3 healthy controls. Site‐specific plaque development was...

  3. Assessment of atherosclerotic plaque inflammation can be improved by delayed time point FDG PET CT imaging

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene;

    2013-01-01

    contrast between plaque activity and blood pool activity over time. Global aortic uptake of 18-FDG was quantified by subtracting the blood pool SUVmean from aortic SUVmax (cSUV). The change in aortic TBR and cSUV over time was determined by a Student’s paired t-test. Regression coefficients summarized the...... data. Results: At 90 minutes, the aortic TBR was 2.072 ± 0.599. At 180 minutes, the aortic TBR significantly increased to 3.488 ± 1.138 (P = <0.0001). At 90 minutes, the aortic cSUV was 1.122 ± 0.505. A significant relationship was observed between aortic cSUV, aging (β = 0.019; t = 2.79; df = 12; P...... = 0.016) and gender (β = 0.502; t = 2.30; df = 12; P = 0.040). At 180 minutes, the aortic cSUV significantly increased to 1.524 ± 0.577 (P = <0.0001). This resulted in a more significant relationship between aortic cSUV, aging (β = 0.025; t = 3.44; df = 12; P = 0.005) and gender (β = 0.542; t = 2...

  4. The effect of interleukin and matrix metalloproteinase on the vulnerability of carotid atherosclerotic plaque and cerebral infarction

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    HUANG Yan

    2012-06-01

    Full Text Available Objective To investigate the relationship of IL-17, IL-10 and MMP-12 with the vulnerability of carotid atherosclerotic plaque and cerebral infarction. Methods According to clinical stroke event 70 carotid atherosclersis patients were divided into asymptomatic carotid atherosclerosis (ACAS group (n = 35 and acute atherosclerotic cerebral infarction (AACI group (n = 35. The patients were also divided into vulnerable plague (VP group (n = 38 and unvulnerable plague (UVP group (n = 32 by color ultrasonic technique. Normal control group (n = 35 was established. The plasma levels of cytokines were tested by enzyme-linked immunosorbent assay (ELISA. Results Compared with the control group, the concentrations of IL-17, IL-10 and MMP-12 in ACAS group and AACI group were significantly elevated (P = 0.000; P = 0.000, moreover, the concentrations of IL-17 and MMP-12 in AACI group were higher than those in ACAS group (P = 0.000; P = 0.002, respectively. In AACI group, the level of IL-10 was lower than the ACAS group and control group (P = 0.000, for all, whereas, no significant difference of IL-10 level was seen between ACAS group and control group (P = 0.275. In VP group, the concentrations of IL-17 and MMP-12 were higher than those in UVP group (P = 0.000 and 0.014, respectively. In VP group, the level of IL-10 was lower than that in UVP group and control group (P = 0.000, for all, but no significant difference of IL-10 level was seen between UVP group and control group (P = 0.742. Correlation analysis showed, the level of IL-17 was positively correlated with the level of MMP-12 (r = 0.640, P = 0.000, and was negatively correlated with the level of IL-10 (r =-0.430, P = 0.000. The level of MMP-12 was weakly negatively correlated with the level of IL-10 (r =-0.242, P = 0.013. Conclusion IL-17, IL-10 and MMP-12 all participate the pathological process of atherosclerosis and cerebral infarction. The elevated IL-17 and MMP-12 levels and decreased IL-10 level

  5. Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques

    International Nuclear Information System (INIS)

    Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of 99mTc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG3 and negative control IgG3 were radiolabelled with 99mTc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield 99mTc-MT1-MMP mAb and 99mTc-IgG3, respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed. 99mTc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional 99mTc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p 99mTc-IgG3 accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest 99mTc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 ± 1.9, %ID x BW/mm2 x 102), followed in decreasing order by fibroatheromatous (1.8 ± 1.3), collagen-rich (1.6 ± 1.0) and neointimal lesions (1.5 ± 1.5). In contrast, 99mTc-IgG3 accumulation was almost independent of the histological grade of lesions. Higher 99mTc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with 99mTc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required. (orig.)

  6. 颈动脉粥样硬化斑块与血浆纤维蛋白原的关系%Relationship between Carotid Atherosclerotic Plaque and Plasma Fibrinogen

    Institute of Scientific and Technical Information of China (English)

    戴志刚; 王涛; 武文元

    2011-01-01

    [ Objective ] To study the relationship between carotid atherosclerosis and plasma fibrinogen. [ Methods] Color Doppler was carried out on carotid artery of 65 carotid atherosclerotic patients, recording position, echo intensity of artherosclerotic plaque,carotid artery intima-media thickness and vessel inside diameter. According to carotid artery stenosis, the patients were divided into 4 groups, and were re-divided into 2 groups ( hard plaque and soft plaque ) on the basis of character of atherosclerotic plaque, meanwhile, detecting the level of plasma fibrinogen, and performing statistical analysis. [ Results ] With the increasing level of plasma fibrinogen , the degree of carotid atherosclerotic stenosis was increased, showing positive correlation; the rate of plasma fibrinogen soft plaque of middle and high density groups is obviously higher than the lower density group. [ Conclusion ] Plasma fibrinogen level is closely correlated with characteristic of carotid atherosclerotic plaque. Plasma fibrinogen may determine the stability of carotid atherosclerotic plaque. And the increasing level of plasma fibrinogen is closely related with carotid atherosclerosis and plays an important role in its development.%目的 探讨患者颈动脉粥样硬化程度以及颈动脉粥样硬化性质与血浆纤维蛋白原的关系.方法 对存在颈动脉粥样硬化的65例患者进行颈动脉彩色多普勒检查,记录颈动脉粥样硬化斑块的部位、回声强度、颈总动脉分叉处内膜中层厚度及血管内径,并根据颈动脉狭窄程度分为4组,再根据超声检查动脉硬化斑块性质分为硬斑和软斑2组,同时检测血浆纤维蛋白原水平,进行统计学分析.结果 随着血浆纤维蛋白原水平的升高,动脉粥样硬化狭窄程度也随之增加,且呈正相关;中、高浓度纤维蛋白原组软斑发生率明显多于低浓度组.结论 血浆纤维蛋白原水平与颈动脉粥样硬化斑块的性质有关,血浆纤维蛋

  7. Interobserver agreement for the detection of atherosclerotic plaque in coronary CT angiography: comparison of two low-dose image acquisition protocols with standard retrospectively ECG-gated reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Schuhbaeck, Annika; Rixe, Johannes; Hamm, Christian [University of Giessen, Department of Cardiology, Giessen (Germany); Marwan, Mohamed; Gauss, Soeren; Muschiol, Gerd; Ropers, Dieter; Daniel, Werner G.; Achenbach, Stephan [University of Erlangen, Department of Cardiology, Erlangen (Germany); Schneider, Christian [University of Giessen, Department of Radiology, Giessen (Germany); Lell, Michael [University of Erlangen, Department of Radiology, Erlangen (Germany)

    2012-07-15

    We compared the interobserver variability concerning the detection of calcified and non-calcified plaque in two different low-dose and standard retrospectively gated protocols for coronary CTA. 150 patients with low heart rates and less than 100 kg body weight were randomised and examined by contrast-enhanced dual-source CT coronary angiography (100 kV, 320 mAs). 50 patients were examined with prospectively ECG-triggered axial acquisition, 50 patients with prospectively ECG-triggered high pitch spiral acquisition, and 50 patients using spiral acquisition with retrospective ECG gating. Two investigators independently analysed the datasets concerning the presence of calcified and non-calcified plaque on a per-segment level. Mean effective dose was 1.4 {+-} 0.2 mSv for axial, 0.8 {+-} 0.07 mSv for high-pitch spiral, and 5.3 {+-} 2.6 mSV for standard spiral acquisition (P < 0.0001). In axial acquisition, interobserver agreement concerning the presence of atherosclerotic plaque was achieved in 650/749 coronary segments (86.8%). In high-pitch spiral acquisition, agreement was achieved in 664/748 segments (88.8%, n.s.). In standard spiral acquisition, agreement was achieved in 672/738 segments (91.0%, P < 0.0001). Interobserver agreement was significantly higher for calcified than for non-calcified plaque in all data acquisition modes. Low-dose coronary CT angiography permits the detection of coronary atherosclerotic plaque with good interobserver agreement. (orig.)

  8. Evaluation by multislice computed tomography of atherosclerotic coronary artery plaques in non-culprit, remote coronary arteries of patients with acute coronary syndrome

    International Nuclear Information System (INIS)

    Patients with acute coronary syndrome (ACS) frequently have vulnerable plaques in the remote coronary arteries, suggesting that ACS is part of the pan-coronary process. In the present study the computed tomography (CT) plaque density in non-culprit atherosclerotic coronary artery lesions was evaluated by multi-slice computed tomography (MSCT) in patients with ACS and non-ACS. MSCT was performed in 21 patients with ACS and 53 patients with non-ACS: 16 of the 21 ACS patients (76%) and 30 of the non-ACS 53 patients (57%) had non-calcified plaques in the non-culprit coronary arteries (p=0.18). CT-low-density plaques (CT density <68 Hounsfield units (HU)) were more frequent in the ACS group (13/16 patients, 81%) than in the non-ACS group (13/30 patients, 43%, p=0.03). In addition, the CT density of the non-culprit lesion was significantly lower in patients with ACS than in those with non-ACS (44.1±22.9 and 77.3±33.7 HU, respectively). Patients with ACS more frequently had CT-low-density plaques in the non-culprit, remote arteries than those with non-ACS, which suggests that ACS treatment should focus not only on stabilizing the culprit lesion but also on systemic stabilization of non-culprit lesions. (author)

  9. Cholesterol-independent effects of atorvastatin prevent cardiovascular morbidity and mortality in a mouse model of atherosclerotic plaque rupture.

    Science.gov (United States)

    Roth, Lynn; Rombouts, Miche; Schrijvers, Dorien M; Martinet, Wim; De Meyer, Guido R Y

    2016-05-01

    Because cholesterol-independent effects of statins are difficult to determine in patients, we studied these pleiotropic effects in apolipoprotein E-deficient (ApoE(-/-)) mice with a mutation in the fibrillin-1 gene (Fbn1(C1039G+/-)). These mice develop exacerbated atherosclerosis and spontaneous plaque ruptures, accompanied by myocardial infarctions (MI) and sudden death. ApoE(-/-)Fbn1(C1039G+/-) mice were fed a Western diet (WD). At week 10 of WD, mice were divided in a control (WD), atorvastatin (10mg/kg/day + WD) and cholesterol withdrawal group (cholW, normal chow). The latter was included to compare the effects of atorvastatin with dietary lipid lowering. Fifteen weeks later, the mice were sacrificed. CholW, but not atorvastatin, reduced plasma cholesterol. Survival increased from 50% to 90% both in cholW and atorvastatin treated mice. CholW as well as atorvastatin treatment increased plaque collagen and fibrous cap thickness, but they did not affect the amount of plaque macrophages and T cells. MMP-2 and MMP-9 activity was significantly lower and the expression of MMP-12, TNF-α and IL-1β was strongly reduced in both treatment groups. Blood monocytes and neutrophils returned to baseline levels (ApoE(-/-) mice before the onset of atherosclerosis). Importantly, atorvastatin but not cholW significantly reduced coronary stenosis (from 50 to 28%) and the occurrence of MI (from 43 to 10%). In conclusion, independent of cholesterol lowering, atorvastatin significantly reduced mortality, plaque vulnerability and inflammation to the same extent as cholW. In addition, atorvastatin but not cholW reduced coronary stenosis and the occurrence of MI. These data unequivocally illustrate the significance of the pleiotropic effects of atorvastatin in the prevention of cardiovascular morbidity and mortality. PMID:26826559

  10. The influence of constitutive law choice used to characterise atherosclerotic tissue material properties on computing stress values in human carotid plaques.

    Science.gov (United States)

    Teng, Zhongzhao; Yuan, Jianmin; Feng, Jiaxuan; Zhang, Yongxue; Brown, Adam J; Wang, Shuo; Lu, Qingsheng; Gillard, Jonathan H

    2015-11-01

    Calculating high stress concentration within carotid atherosclerotic plaques has been shown to be complementary to anatomical features in assessing vulnerability. Reliability of stress calculation may depend on the constitutive laws/strain energy density functions (SEDFs) used to characterize tissue material properties. Different SEDFs, including neo-Hookean, one-/two-term Ogden, Yeoh, 5-parameter Mooney-Rivlin, Demiray and modified Mooney-Rivlin, have been used to describe atherosclerotic tissue behavior. However, the capacity of SEDFs to fit experimental data and the difference in the stress calculation remains unexplored. In this study, seven SEDFs were used to fit the stress-stretch data points of media, fibrous cap, lipid and intraplaque hemorrhage/thrombus obtained from 21 human carotid plaques. Semi-analytic solution, 2D structure-only and 3D fully coupled fluid-structure interaction (FSI) analyses were used to quantify stress using different SEDFs and the related material stability examined. Results show that, except for neo-Hookean, all other six SEDFs fitted the experimental points well, with vessel stress distribution in the circumferential and radial directions being similar. 2D structural-only analysis was successful for all seven SEDFs, but 3D FSI were only possible with neo-Hookean, Demiray and modified Mooney-Rivlin models. Stresses calculated using Demiray and modified Mooney-Rivlin models were nearly identical. Further analyses indicated that the energy contours of one-/two-term Ogden and 5-parameter Mooney-Rivlin models were not strictly convex and the material stability indictors under homogeneous deformations were not always positive. In conclusion, considering the capacity in characterizing material properties and stabilities, Demiray and modified Mooney-Rivlin SEDF appear practical choices for mechanical analyses to predict the critical mechanical conditions within carotid atherosclerotic plaques. PMID:26472305

  11. Imaging of atherosclerotic aorta of rabbit model by detection of plaque inflammation with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography

    Institute of Scientific and Technical Information of China (English)

    ZHAO Quan-ming; FENG Ting-ting; ZHAO Xin; XU Zhan-min; LIU Yu; LI De-peng; LI Li-qin; SU Gong; ZHANG Xiao-xia

    2011-01-01

    Background Atherosclerotic plaque rupture is the primary mechanism of thrombosis which plays a key role in the onset of acute coronary syndromes. Detection of these plaques prone to rupture (vulnerable plaque) could be clinically significant for prevention of cardiac events. It has been shown that high metabolism cells have a high uptake of fluorine-18 fluorodeoxyglucose (18F-FDG). The objective of this study was to investigate the correlation of FDG uptake and the immuno-histochemistry parameters of plaques, and the effect of atorvastatin on vulnerable atherosclerotic plaque in a rabbit model.Methods Ten male New Zealand White rabbits were divided into three groups as follows: (1) normal control group (n=2,C group): the animals were fed a standard diet at 120 g/d and were given water ad labium; (2) atherosclerosis group (n=4,As group): animals were fed with high fat diet for 5 months after aortic endothelia damage; (3) treatment group (atherosclerosis + atorvastatin, n=4, Statin group): animals were fed with high fat diet for 5 months and then changed into normal chow plus atorvastatin (2.5 mg·d-1·kg-1) treatment for another 4 months. Then these four rabbits were imaged with fluorine-18 fluorodexyglucose positron emission tomography/computed tomography (PET/CT) and sacrificed for pathohistologic studies. FDG uptake by the aorta was expressed as target-to-background ratio (TBR). Maximal standardized uptake value (SUV) was measured over the thoracic and abdominal aortas. The aortic smooth muscle cell (SMC) number, CD-14 antibody positive cell (macrophage) number and the ratio of the thickness of fibrous cap to the thickness of lipid core (cap-to-core ratio) in atherosclerotic plaques were analyzed.Results As group showed significantly higher uptake of FDG than C group (SUVs: 0.746±0.172 vs. 0.286±0.073, P <0.001). After 4 months of atorvastatin treatment and the modification of diet, SUVs decreased significantly (Statin group:0.550±0.134, compared to As group

  12. Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture

    OpenAIRE

    Lee, K.; Santibanez-Koref, M; Polvikoski, T; BIRCHALL, D; Mendelow, A D; Keavney, B.

    2013-01-01

    Objective Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. Methods and results We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptu...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-15

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

  14. Advantage in Bright-blood and Black-blood Magnetic Resonance Imaging with High-resolution for Analysis of Carotid Atherosclerotic Plaques

    Directory of Open Access Journals (Sweden)

    Mei Li

    2015-01-01

    Full Text Available Background: About 50% of the cerebral ischemia events are induced by intracranial and extracranial atherosclerosis. This study aimed to evaluate the feasibility and accuracy for displaying atherosclerotic plaques in carotid arteries and analyzing their ingredients by using high-resolution new magnetic resonance imaging (MRI techniques. Methods: Totally, 49 patients suspected of extracranial carotid artery stenosis were subjected to cranial MRI scan and magnetic resonance angiography (MRA examination on carotid arteries, and high-resolution bright-blood and black-blood MRI analysis was carried out within 1 week. Digital subtraction angiography (DSA examination was carried out for 16 patients within 1 month. Results: Totally, 103 plaques were detected in the 49 patients, which were characterized by localized or diffusive thickening of the vessel wall, with the intrusion of crescent-shaped abnormal signal into lumens. Fibrous cap was displayed as isointensity in T1-weighted image (T1WI and hyperintensities in proton density weighted image (PDWI and T2-weighted image (T2WI, lipid core was displayed as isointensity or slight hyperintensities in T1WI, isointensity, hyperintensities or hypointensity in PDWI, and hypointensity in T2WI. Calcification in plaques was detected in 11 patients. Eight patients were detected with irregular plaque surface or ulcerative plaques, which were characterized by irregular intravascular space surface in the black-blood sequences, black hypointensity band was not detected in three-dimensional time-of-flight, or the hypointensity band was not continuous, and intrusion of hyperintensities into plaques can be detected. Bright-blood and black-blood techniques were highly correlated with the diagnosis of contrast-enhanced MRA in angiostenosis degree, Rs = 0.97, P < 0.001. In comparison to DSA, the sensitivity, specificity, and accuracy of MRI diagnosis of stenosis for ≥50% were 88.9%, 100%, and 97.9%, respectively

  15. Disturbed flow mediated modulation of shear forces on endothelial plane: A proposed model for studying endothelium around atherosclerotic plaques

    Science.gov (United States)

    Balaguru, Uma Maheswari; Sundaresan, Lakshmikirupa; Manivannan, Jeganathan; Majunathan, Reji; Mani, Krishnapriya; Swaminathan, Akila; Venkatesan, Saravanakumar; Kasiviswanathan, Dharanibalan; Chatterjee, Suvro

    2016-06-01

    Disturbed fluid flow or modulated shear stress is associated with vascular conditions such as atherosclerosis, thrombosis, and aneurysm. In vitro simulation of the fluid flow around the plaque micro-environment remains a challenging approach. Currently available models have limitations such as complications in protocols, high cost, incompetence of co-culture and not being suitable for massive expression studies. Hence, the present study aimed to develop a simple, versatile model based on Computational Fluid Dynamics (CFD) simulation. Current observations of CFD have shown the regions of modulated shear stress by the disturbed fluid flow. To execute and validate the model in real sense, cell morphology, cytoskeletal arrangement, cell death, reactive oxygen species (ROS) profile, nitric oxide production and disturbed flow markers under the above condition were assessed. Endothelium at disturbed flow region which had been exposed to low shear stress and swirling flow pattern showed morphological and expression similarities with the pathological disturbed flow environment reported previously. Altogether, the proposed model can serve as a platform to simulate the real time micro-environment of disturbed flow associated with eccentric plaque shapes and the possibilities of studying its downstream events.

  16. Distribution of ultrasonic radiofrequency signal amplitude detects lipids in atherosclerotic plaque of coronary arteries: an ex-vivo study

    Directory of Open Access Journals (Sweden)

    Moroi Masao

    2008-05-01

    Full Text Available Abstract Background Accumulation of lipids within coronary plaques is an important process in disease progression. However, gray-scale intravascular ultrasound images cannot detect plaque lipids effectively. Radiofrequency signal analysis could provide more accurate information on preclinical coronary plaques. Methods We analyzed 29 zones of mild atheroma in human coronary arteries acquired at autopsy. Two histologic groups, i.e., plaques with a lipid core (group L and plaques without a lipid core (group N, were analyzed by automatic calculation of integrated backscatter. One hundred regions of interest were set on the target zone. Radiofrequency signals from a 50 MHz transducer were digitized at 240 MHz with 12-bit resolution. The intensity of integrated backscatter and its distribution within each plaque were compared between the two groups. Results Although the mean backscatter was similar between the groups, intraplaque variation of backscatter and backscatter in the axial direction were larger in group L than in group N (p = 0.02. Conventional intravascular ultrasound showed extremely low sensitivity for lipid detection, despite a high specificity. In contrast, a cut-off value>32 for the total variance of integrated backscatter identified lipid-containing plaque with a high sensitivity (85% and specificity (75%. Conclusion Compared with conventional imaging, assessment of the intraplaque distribution of integrated backscatter is more effective for detecting lipid. As coronary atheroma progresses, its composition becomes heterogeneous and multi-layered. This radiofrequency technique can portray complex plaque histology and can detect the early stage of plaque progression.

  17. 动脉粥样硬化易损斑块的动物模型和检测技术%Animal Models and Detection Technologies of Vulnerable Atherosclerotic Plaques

    Institute of Scientific and Technical Information of China (English)

    陈文强; 张运

    2016-01-01

    Vulnerable atherosclerotic plaque rupture leading to thrombosis is the major cause of acute coronary syndromes.While early detection or prevention the vulnerable plaque would be the only way to reduce the risk of this catastrophic life-threatening event,there is frustratingly little progress in either.Lack of suitable animal models has considerably hampered the research progress in understanding the mechanisms occurring in the development of plaque rupture.This review summarizes the currently available vulnerable plaque animal models and invasive and noninvasive imaging modalities used to detect vulnerable plaques,including high frequency duplex ultrasound,coronary tomographic angiography (CTA),magnetic resonance imaging (MRI),intravascular ultrasound (IVUS),optical coherence tomography (OCT),intravascular ultrasound elastography,and inflammatory markers.%动脉粥样硬化易损斑块破裂、血栓形成是急性冠状动脉综合征的发病机制已成为共识.由于缺乏理想的易损斑块的动物模型,对斑块破裂前的血清学及影像学特征研究较少,尚缺乏能够早期识别易损斑块及预防斑块破裂的最佳方法.本实验室已成功构建家兔和ApoE-/-小鼠的易损斑块模型.易损斑块的检测技术主要包括非侵入性及侵入性的影像学检测及功能学检测技术.对易损斑块的早期准确识别以便及时干预具有十分重要的临床意义.

  18. Mast cell degranulator compound 48-80 promotes atherosclerotic plaque in apolipoprotein E knockout mice with perivascular common carotid collar placement

    Institute of Scientific and Technical Information of China (English)

    TANG Ya-ling; YANG Yong-zong; WANG Shuang; HUANG Tao; TANG Chao-ke; XU Zeng-xiang; SUN Yu-hui

    2009-01-01

    Background Study of the relationship between mast cells and atherosclerosis is mostly dependent on pathological observation and cytology experiments. To investigate the effects of mast cells degranulation on plaque and their possible mechanisms we used apolipoprotein E knockout mice which had been placed perivascular common carotid collar with mast cells degranulator compound 48-80.Methods Forty apolipoprotein E knockout mice were fed a western-type diet and operated on with placement of perivascular right common carotid collar. Four weeks after surgery, the mice were intraperitoneally injected with compound 48-80 (0.5 mg/kg) or D-Hanks every other day for 4 times. The serum lipids and activity of tryptase were measured. Tissue sections were stained with hematoxylin and eosin. Corresponding sections were stained with toluidine blue and immunohistochemically with antibodies against macrophage-specific antigen, α-smooth muscle actin, interleukin-1β and van Willebrand factor. Simultaneously, basic fibroblast growth factor was detected by in situ hybridization and immunofluorescence.Results No pathological change was observed in common carotid non-collar placement but atherogenesis in common carotid collar placement of both groups. There was a significant increase in plaque area ((5.85±0.75)×104 vs (0.86±0.28)×104 μm2, P<0.05), the degree of lumen stenosis ((81±15)% vs (41±12)%, P <0.05), the activity of tryptase in serum ((0.57±0.13) U/L vs (0.36±0.10) U/L, P <0.05), and the percentage of degranulated mast cells ((80.6±17.8)% vs (13.5±4.1)%, P <0.05). The expressions of macrophage-specific antigen, α-smooth muscle actin, interleukin-1β, basic fibroblast growth factor and the density of neovessel in plaque were more in the compound 48-80 group than in the control group.Conclusions Perivascular common carotid collar placement can promote atherosclerotic plaque formation in apolipoprotein E knockout mice. Compound 48-80 increases plaque area and the degree

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

    DEFF Research Database (Denmark)

    Iversen, Kasper; Teisner, Ane; Dalager, Soren;

    2011-01-01

    To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A.......To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A....

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

    DEFF Research Database (Denmark)

    Iversen, Kasper K; Teisner, Ane Søgaard; Dalager, Soren;

    2011-01-01

    OBJECTIVE: To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A. DESIGN AND METHODS: Vulnerable plaques and control tissues were examined by immunohistochemistry. Volunteers and...

  1. A direct vulnerable atherosclerotic plaque elasticity reconstruction method based on an original material-finite element formulation: theoretical framework

    International Nuclear Information System (INIS)

    The peak cap stress (PCS) amplitude is recognized as a biomechanical predictor of vulnerable plaque (VP) rupture. However, quantifying PCS in vivo remains a challenge since the stress depends on the plaque mechanical properties. In response, an iterative material finite element (FE) elasticity reconstruction method using strain measurements has been implemented for the solution of these inverse problems. Although this approach could resolve the mechanical characterization of VPs, it suffers from major limitations since (i) it is not adapted to characterize VPs exhibiting high material discontinuities between inclusions, and (ii) does not permit real time elasticity reconstruction for clinical use. The present theoretical study was therefore designed to develop a direct material-FE algorithm for elasticity reconstruction problems which accounts for material heterogeneities. We originally modified and adapted the extended FE method (Xfem), used mainly in crack analysis, to model material heterogeneities. This new algorithm was successfully applied to six coronary lesions of patients imaged in vivo with intravascular ultrasound. The results demonstrated that the mean relative absolute errors of the reconstructed Young's moduli obtained for the arterial wall, fibrosis, necrotic core, and calcified regions of the VPs decreased from 95.3±15.56%, 98.85±72.42%, 103.29±111.86% and 95.3±10.49%, respectively, to values smaller than 2.6 × 10−8±5.7 × 10−8% (i.e. close to the exact solutions) when including modified-Xfem method into our direct elasticity reconstruction method. (paper)

  2. The Clinical Value of High-Intensity Signals on the Coronary Atherosclerotic Plaques: Noncontrast T1-Weighted Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Shoichi Ehara

    2016-07-01

    Full Text Available Over the past several decades, significant progress has been made in the pathohistological assessment of vulnerable plaques and in invasive intravascular imaging techniques. However, the assessment of plaque morphology by invasive modalities is of limited value for the detection of subclinical coronary atherosclerosis and the subsequent prediction or prevention of acute cardiovascular events. Recently, magnetic resonance (MR imaging technology has reached a sufficient level of spatial resolution, which allowed the plaque visualization of large and static arteries such as the carotids and aorta. However, coronary wall imaging by MR is still challenging due to the small size of coronary arteries, cardiac and respiratory motion, and the low contrast-to-noise ratio between the coronary artery wall and the surrounding structures. Following the introduction of carotid plaque imaging with noncontrast T1-weighted imaging (T1WI, some investigators have reported that coronary artery high-intensity signals on T1WI are associated with vulnerable plaque morphology and an increased risk of future cardiac events. Although there are several limitations and issues that need to be resolved, this novel MR technique for coronary plaque imaging could influence treatment strategies for atherothrombotic disease and may be useful for understanding the pathophysiological mechanisms of atherothrombotic plaque formation.

  3. Mathematical modelling of atheroma plaque formation and development in coronary arteries

    Science.gov (United States)

    Cilla, Myriam; Peña, Estefanía; Martínez, Miguel A.

    2014-01-01

    Atherosclerosis is a vascular disease caused by inflammation of the arterial wall, which results in the accumulation of low-density lipoprotein (LDL) cholesterol, monocytes, macrophages and fat-laden foam cells at the place of the inflammation. This process is commonly referred to as plaque formation. The evolution of the atherosclerosis disease, and in particular the influence of wall shear stress on the growth of atherosclerotic plaques, is still a poorly understood phenomenon. This work presents a mathematical model to reproduce atheroma plaque growth in coronary arteries. This model uses the Navier–Stokes equations and Darcy's law for fluid dynamics, convection–diffusion–reaction equations for modelling the mass balance in the lumen and intima, and the Kedem–Katchalsky equations for the interfacial coupling at membranes, i.e. endothelium. The volume flux and the solute flux across the interface between the fluid and the porous domains are governed by a three-pore model. The main species and substances which play a role in early atherosclerosis development have been considered in the model, i.e. LDL, oxidized LDL, monocytes, macrophages, foam cells, smooth muscle cells, cytokines and collagen. Furthermore, experimental data taken from the literature have been used in order to physiologically determine model parameters. The mathematical model has been implemented in a representative axisymmetric geometrical coronary artery model. The results show that the mathematical model is able to qualitatively capture the atheroma plaque development observed in the intima layer. PMID:24196695

  4. Mathematical modelling of atheroma plaque formation and development in coronary arteries.

    Science.gov (United States)

    Cilla, Myriam; Peña, Estefanía; Martínez, Miguel A

    2014-01-01

    Atherosclerosis is a vascular disease caused by inflammation of the arterial wall, which results in the accumulation of low-density lipoprotein (LDL) cholesterol, monocytes, macrophages and fat-laden foam cells at the place of the inflammation. This process is commonly referred to as plaque formation. The evolution of the atherosclerosis disease, and in particular the influence of wall shear stress on the growth of atherosclerotic plaques, is still a poorly understood phenomenon. This work presents a mathematical model to reproduce atheroma plaque growth in coronary arteries. This model uses the Navier-Stokes equations and Darcy's law for fluid dynamics, convection-diffusion-reaction equations for modelling the mass balance in the lumen and intima, and the Kedem-Katchalsky equations for the interfacial coupling at membranes, i.e. endothelium. The volume flux and the solute flux across the interface between the fluid and the porous domains are governed by a three-pore model. The main species and substances which play a role in early atherosclerosis development have been considered in the model, i.e. LDL, oxidized LDL, monocytes, macrophages, foam cells, smooth muscle cells, cytokines and collagen. Furthermore, experimental data taken from the literature have been used in order to physiologically determine model parameters. The mathematical model has been implemented in a representative axisymmetric geometrical coronary artery model. The results show that the mathematical model is able to qualitatively capture the atheroma plaque development observed in the intima layer. PMID:24196695

  5. Ultrasound and Biochemical Diagnostic Tools for the Characterization of Vulnerable Carotid Atherosclerotic Plaque.

    Science.gov (United States)

    Lechareas, Simeon; Yanni, Amalia E; Golemati, Spyretta; Chatziioannou, Achilles; Perrea, Despoina

    2016-01-01

    Stroke is a leading cause of morbidity and mortality worldwide, and characterization of vulnerable carotid plaque remains the spearhead of scientific research. Plaque destabilization, the key factor that induces the series of events leading to the clinical symptoms of carotid artery disease, is a consequence of complex mechanical, structural and biochemical processes. Novel imaging and molecular markers have been studied as predictors of disease outcome with promising results. The aim of this review is to present the current state of research on the association between ultrasound-derived echogenicity indices and blood parameters indicative of carotid plaque stability and activity. Bibliographic research revealed that there are limited available data. Among the biomarkers studied, those related to oxidative stress, lipoproteins and diabetes/insulin resistance are associated with echolucent plaques, whereas adipokines are associated with echogenic plaques. Biomarkers of inflammation and coagulation have not exhibited any conclusive relationship with plaque echogenicity, and it is not possible to come to any conclusion regarding calcification-, apoptosis- and neo-angiogenesis-related parameters because of the extremely limited bibliographic data. PMID:26493239

  6. {sup 99m}Tc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Annovazzi, Alessio; D' Alessandria, Calogero; Scopinaro, Francesco [University La Sapienza, Nuclear Medicine, 2nd Faculty of Medicine, Rome (Italy); Bonanno, Elena; Spagnoli, Luigi G. [University Tor Vergata, Department of Biopathology and Diagnostic Imaging, Rome (Italy); Arca, Marcello [University La Sapienza, Department of Clinical and Applied Medical Therapy, 1st Faculty of Medicine, Rome (Italy); Marcoccia, Antonella; Violi, Francesco [University La Sapienza, Medical Clinical Institute 1, 1st Faculty of Medicine, Rome (Italy); Toma, Giorgio De [University La Sapienza, Department of Surgery Pietro Valdoni, 1st Faculty of Medicine, Rome (Italy); Signore, Alberto [University La Sapienza, Nuclear Medicine, 2nd Faculty of Medicine, Rome (Italy); University of Groningen, Department of Nuclear Medicine, Groningen (Netherlands); Ospedale S. Andrea, Nuclear Medicine, Roma (Italy)

    2006-02-01

    Several histopathological studies have demonstrated that vulnerable plaques are enriched in inflammatory cells. The aims of this study were: (1a) to test the ability of {sup 99m}Tc-labelled interleukin-2 ({sup 99m}Tc-IL2) to bind to IL2R-positive (IL2R+) cells in carotid plaques and (1b) to correlate the plaque uptake of {sup 99m}Tc-IL2, measured in vivo, with the number of IL2R+ cells within the plaque, measured ex vivo by histology (transversal study, TS), and (2) to evaluate changes in {sup 99m}Tc-IL2 uptake in plaques, before and after treatment with a statin or a hypocholesterolaemic diet (longitudinal study, LS). Ultrasound scan was performed for plaque characterisation and localisation. Fourteen patients (16 plaques) eligible for endoarterectomy were recruited for the TS and underwent {sup 99m}Tc-IL2 scintigraphy before surgery. Nine patients (13 plaques) were recruited for the LS; these patients received atorvastatin or a standard hypocholesterolaemic diet and {sup 99m}Tc-IL2 scintigraphy was performed before and after 3 months of treatment. The degree of {sup 99m}Tc-IL2 uptake was expressed as the plaque/background (T/B) ratio. In patients from TS, T/B ratios correlated with the percentage of IL2R+ cells at histology (r=0.707; p=0.002) and the number of IL2R+ cells at flow cytometry (r=0.711; p=0.006). No correlations were observed between ultrasound scores and either scintigraphic or histological findings. In patients from the LS, the mean {sup 99m}Tc-IL2 uptake decreased in statin-treated patients (1.75{+-}0.50 vs 2.16{+-}0.44; p=0.012), while it was unchanged in the patients on the hypocholesterolaemic diet (2.33{+-}0.45 vs 2.34{+-}0.5). {sup 99m}Tc-IL2 accumulates in vulnerable carotid plaques; this accumulation is correlated with the amount of IL2R+ cells and is influenced by lipid-lowering treatment with a statin. (orig.)

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Gajda, Mariusz; Kowalska, Joanna; Banaś, Agnieszka; Banaś, Krzysztof; Kwiatek, Wojciech M.; Kostogrys, Renata B.; Mateuszuk, łukasz; ChŁopicki, Stefan; Litwin, Jan A.; Appel, Karen

    2011-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-15

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

  10. Lumen segmentation and motion estimation in B-mode and contrast-enhanced ultrasound images of the carotid artery in patients with atherosclerotic plaque.

    Science.gov (United States)

    Carvalho, Diego D B; Akkus, Zeynettin; van den Oord, Stijn C H; Schinkel, Arend F L; van der Steen, Antonius F W; Niessen, Wiro J; Bosch, Johan G; Klein, Stefan

    2015-04-01

    In standard B-mode ultrasound (BMUS), segmentation of the lumen of atherosclerotic carotid arteries and studying the lumen geometry over time are difficult owing to irregular lumen shapes, noise, artifacts, and echolucent plaques. Contrast enhanced ultrasound (CEUS) improves lumen visualization, but lumen segmentation remains challenging owing to varying intensities, CEUS-specific artifacts and lack of tissue visualization. To overcome these challenges, we propose a novel method using simultaneously acquired BMUS&CEUS image sequences. Initially, the method estimates nonrigid motion (NME) from the image sequences, using intensity-based image registration. The motion-compensated image sequence is then averaged to obtain a single "epitome" image with improved signal-to-noise ratio. The lumen is segmented from the epitome image through an intensity joint-histogram classification and a graph-based segmentation. NME was validated by comparing displacements with manual annotations in 11 carotids. The average root mean square error (RMSE) was 112±73 μm . Segmentation results were validated against manual delineations in the epitome images of two different datasets, respectively containing 11 (RMSE 191±43 μm) and 10 (RMSE 351±176 μm ) carotids. From the deformation fields, we derived arterial distensibility with values comparable to the literature. The average errors in all experiments were in the inter-observer variability range. To the best of our knowledge, this is the first study exploiting combined BMUS&CEUS images for atherosclerotic carotid lumen segmentation. PMID:25423650

  11. Grating-based X-ray phase-contrast tomography of atherosclerotic plaque at high photon energies

    International Nuclear Information System (INIS)

    Background: Tissue characterization of atherosclerosis by absorption-based imaging methods is limited due to low soft-tissue contrast. Grating-based phase-contrast computed tomography (PC-CT) may become an alternative for plaque assessment if the phase signal can be retrieved at clinically applicable photon energies. The aims of this feasibility study were (i) to characterize arterial vessels at low and high photon energies, (ii) to extract qualitative features and (iii) quantitative phase-contrast Hounsfield units (HU-phase) of plaque components at 53 keV using histopathology as gold standard. Materials and methods: Five human carotid artery specimens underwent grating-based PC-CT using synchrotron radiation of either 23 keV or 53 keV and histological work-up. Specimens without advanced atherosclerosis were used to extract signal criteria of vessel layers. Diseased specimens were screened for important plaque components including fibrous tissue (FT), lipid (LIP), necrotic core (NEC), intraplaque hemorrhage (IPH), inflammatory cell infiltration (INF) and calcifications (CA). Qualitative features as well as quantitative HU-phase were analyzed. Results: Thirty-three regions in 6 corresponding PC-CT scans and histology sections were identified. Healthy samples had the same signal characteristics at 23 keV and 53 keV with bright tunica intima and adventitia and dark media. Plaque components showed differences in signal intensity and texture at 53 keV. Quantitative analysis demonstrated the highest HU-phase of soft plaque in dense FT. Less organized LIP, NEC and INF were associated with lower HU-phase values. The highest HU-phase were measured in CA. Conclusion: PC-CT of atherosclerosis is feasible at high, clinically relevant photon energies and provides detailed information about plaque structure including features of high risk vulnerable plaques. (orig.)

  12. The effect of lipid regulation with atorvastatin on the blood lipid levels and carotid artery plaques in patients with atherosclerotic cerebral infarction

    Directory of Open Access Journals (Sweden)

    Shu XU

    2015-11-01

    Full Text Available Objective To analyze the effect of intensive lipid regulation treatment with atorvastatin on the blood lipid levels and carotid artery plaques in patients with atherosclerotic cerebral infarction.  Methods Ninety-two patients with atherosclerotic cerebral infarction were randomly divided into two groups: observation group (treated by atorvastatin calcium with the dosage of 20 mg/d, N = 46 and control group (treated by diet without lipid-rich food, N=46. Besides, other drugs given to the patients in two groups were the same. The blood lipid levels and the changes of carotid artery plaques in two groups were analyzed and compared before treatment and 3 months after treatment. Results After treatment, the concentrations of total cholesterol [TC, (4.23 ± 0.92 mmol/L vs (5.24 ± 0.68 mmol/L], triglyceride [TG, (2.46 ± 0.28 mmol/L vs (3.33 ± 0.47 mmol/L], low-density lipoprotein cholesterol [LDL-C, (2.52 ± 0.38 mmol/L vs (4.78 ± 0.86 mmol/L] in the patients of observation group were all decreased and significantly lower than those in the control group (P = 0.000, for all, and the concentration of high-density lipoprotein cholesterol [HDL-C, (1.13 ± 0.41 mmol/L vs (0.85 ± 0.32 mmol/L] in the patients of observation group was increased and significantly than that in the control group (P = 0.003. The carotid artery plaque size [(20.25 ± 0.32 mm2 vs (24.42 ± 10.33 mm2] and thickness [(0.59 ± 0.13 mm vs (1.93 ± 0.23 mm] of carotid artery plaques and intima?media thickness [IMT, (1.32 ± 0.67 mm vs (1.63 ± 0.56 mm] of common carotid artery (CCA in the patients of observation group were all significantly lower than those in patients in the control group (P = 0.000, 0.000, 0.010, respectively. Comparing serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, creatine kinase (CK and creatinine (Cr levels after treatment with before treatment, there was no significant difference between 2 groups (P > 0.05, for all.  Conclusions

  13. Assessment of atherosclerotic plaque collagen content and architecture using polarization-sensitive optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Doradla, Pallavi; Villiger, Martin; Tshikudi, Diane M.; Bouma, Brett E.; Nadkarni, Seemantini K.

    2016-02-01

    Acute myocardial infarction, caused by the rupture of vulnerable coronary plaques, is the leading cause of death worldwide. Collagen is the primary extracellular matrix macromolecule that imparts the mechanical stability to a plaque and its reduction causes plaque instability. Intracoronary polarization sensitive optical coherence tomography (PS-OCT) measures the polarization states of the backscattered light from the tissue to evaluate plaque birefringence, a material property that is elevated in proteins such as collagen with an ordered structure. Here we investigate the dependence of the PS-OCT parameters on the quantity of the plaque collagen and fiber architecture. In this study, coronary arterial segments from human cadaveric hearts were evaluated with intracoronary PS-OCT and compared with Histopathological assessment of collagen content and architecture from picrosirius-red (PSR) stained sections. PSR sections were visualized with circularly-polarized light microscopy to quantify collagen birefringence, and the additional assessment of color hue indicated fibril thickness. Due to the ordered architecture of thick collagen fibers, a positive correlation between PS-OCT retardation and quantity of thick collagen fibers (r=0.54, p=0.04), and similarly with the total collagen content (r=0.51, p=0.03) was observed. In contrast, there was no perceivable relationship between PS-OCT retardation and the presence of thin collagen fibers (r=0.08, p=0.07), suggesting that thin and disorganized collagen fiber architecture did not significantly contribute to the PS-OCT retardation. Further analysis will be performed to assess the relationship between PS-OCT retardation and collagen architecture based on immunohistochemical analysis of collagen type. These results suggest that intracoronary PS-OCT may open the opportunity to assess collagen architecture in addition total collagen content, potentially enabling an improved understanding of coronary plaque rupture.

  14. Intracoronary Imaging in the Detection of Vulnerable Plaques.

    Science.gov (United States)

    Batty, Jonathan A; Subba, Shristy; Luke, Peter; Gigi, Li Wing Chi; Sinclair, Hannah; Kunadian, Vijay

    2016-03-01

    Coronary artery disease is the result of atherosclerotic changes to the coronary arterial wall, comprising endothelial dysfunction, vascular inflammation and deposition of lipid-rich macrophage foam cells. Certain high-risk atherosclerotic plaques are vulnerable to disruption, leading to rupture, thrombosis and the clinical sequelae of acute coronary syndrome. Though recognised as the gold standard for evaluating the presence, distribution and severity of atherosclerotic lesions, invasive coronary angiography is incapable of identifying non-stenotic, vulnerable plaques that are responsible for adverse cardiovascular events. The recognition of such limitations has impelled the development of intracoronary imaging technologies, including intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy, which enable the detailed evaluation of the coronary wall and atherosclerotic plaques in clinical practice. This review discusses the present status of invasive imaging technologies; summarises up-to-date, evidence-based clinical guidelines; and addresses questions that remain unanswered with regard to the future of intracoronary plaque imaging. PMID:26879196

  15. Quantitative analysis of ultrasound B-mode images of carotid atherosclerotic plaque: correlation with visual classification and histological examination

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Grønholdt, Marie-Louise; Wiebe, Brit;

    1998-01-01

    regions of the plaque in still ultrasound images from three orthogonal scan planes and finally a histological analysis of the surgically removed plaque. The quantitative comparison was made with the linear model and with separation of the available data into training and test sets. The comparison of...... subjective classification with features from still ultrasound images revealed an overall agreement of 60 % for classification of echogenicity and 70 % for classification of structure. Comparison of the histologically determined relative volume of soft materials with features from the still images revealed a...... soft materials for individual patients. Reasons for this is discussed in the paper, together with suggestions for improvements....

  16. Clinical Study on Effect of Garlicin in Stabilizing the Carotid Artery Atherosclerotic Plaque in Patients with Primary Hypertension and Coronary Artery Disease

    Institute of Scientific and Technical Information of China (English)

    CHENG Wen-li; KE Yuan-nan; SHI Zai-xiang; WANG Ying; CHEN Li; JU Gao; FAN Shu-ying

    2006-01-01

    Objective: To investigate the effect of garlicin in treating carotid artery atherosclerotic plaque (CAAP) in patients with primary hypertension and coronary heart disease (PHT-CHD). Methods: Seventynine patients with PHT-CHD were randomly divided into the treated group (39 patients) treated with garlicin and fosinopril and the control group (40 patients) treated with fosinopril alone. The change of CAAP was evaluated by high frequency ultrasonic examination every six months, and the changes of intercellular adhesion molecule-1 (ICAM-1) and high sensitive C-reactive protein (hs-CRP) were measured by ELISA, with the observation proceeding for 52 weeks totally. Results: By the end of the experiment, the number of complex plaques, Crouse integrals, intima-media thickness, serum ICAM-1 and hs-CRP were significantly lower in the treated group than those in the control group with significant difference (P<0.05). Conclusion; Garlicin could stabilize CAAP to a certain extent and shows a definite vascular protective effect in patients with PHT-CHD.

  17. Detection of vulnerable atherosclerotic plaque and prediction of thrombosis events in a rabbit model using 18F-FDG -PET/CT.

    Directory of Open Access Journals (Sweden)

    Quan-ming Zhao

    Full Text Available BACKGROUND: Detection of vulnerable plaques could be clinically significant in the prevention of cardiovascular events. We aimed to compare Fluorine-18 fluorodeoxyglucose ((18F-FDG uptake in vulnerable and stable plaques, and investigate the feasibility of predicting thrombosis events using Positron Emission Tomography/Computed Tomography (PET/CT angiography. METHODS: Atherosclerosis was induced in 23 male New Zealand white rabbits. The rabbits underwent pharmacological triggering to induce thrombosis. A pre-triggered PET/CTA scan and a post-triggered PET/CTA scan were respectively performed. (18F-FDG uptake by the aorta was expressed as maximal standardized uptake value (SUVmax and mean SUV (SUVmean. SUVs were measured on serial 7.5 mm arterial segments. RESULTS: Thrombosis was identified in 15 of 23 rabbits. The pre-triggered SUVmean and SUVmax were 0.768 ± 0.111 and 0.804 ± 0.120, respectively, in the arterial segments with stable plaque, and 1.097 ± 0.189 and 1.229 ± 0.290, respectively, in the arterial segments with vulnerable plaque (P<0.001, respectively. The post-triggered SUVmean and SUVmax were 0.849 ± 0.167 and 0.906 ± 0.191, respectively in the arterial segments without thrombosis, and 1.152 ± 0.258 and 1.294 ± 0.313, respectively in the arterial segments with thrombosis (P<0.001, respectively. The values of SUVmean in the pre-triggered arterial segments were used to plot a receiver operating characteristic curve (ROC for predicting thrombosis events. Area under the curve (AUC was 0.898. Maximal sensitivity and specificity (75.4% and 88.5%, respectively were obtained when SUVmean was 0.882. CONCLUSIONS: Vulnerable and stable plaques can be distinguished by quantitative analysis of (18F-FDG uptake in the arterial segments in this rabbit model. PET/CT may be used for predicting thrombosis events and risk-stratification in patients with atherosclerotic disease.

  18. The role of contrast-enhanced ultrasound (CEUS) in visualizing atherosclerotic carotid plaque vulnerability: Which injection protocol? Which scanning technique?

    Energy Technology Data Exchange (ETDEWEB)

    Iezzi, Roberto, E-mail: roberto.iezzi@rm.unicatt.it [Department of Bioimaging and Radiological Sciences, Institute of Radiology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Petrone, Gianluigi [Institute of Pathology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168, Rome (Italy); Ferrante, Angela [Department of Vascular Surgery, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Lauriola, Libero [Institute of Pathology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168, Rome (Italy); Vincenzoni, Claudio [Department of Vascular Surgery, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Torre, Michele Fabio la [Department of Bioimaging and Radiological Sciences, Institute of Radiology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Snider, Francesco [Department of Vascular Surgery, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Rindi, Guido [Institute of Pathology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168, Rome (Italy); Bonomo, Lorenzo [Department of Bioimaging and Radiological Sciences, Institute of Radiology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy)

    2015-05-15

    Highlights: • CEUS is a safe and efficacious technique for the identification and characterization of carotid plaque. • CEUS represents a diagnostic tool for the management of patients with carotid plaque, particularly in asymptomatic patients. • Improved diagnostic performance is achieved with the injection of 4 mL bolus of contrast-medium. • Improved diagnostic performance is achieved with the use of Dynamic Imaging rather than late-phase imaging. - Abstract: Purpose: To correlate the degree of plaque vulnerability as determined by contrast-enhanced ultrasound (CEUS) with histological findings. Secondary objectives were to optimize the CEUS acquisition technique and image evaluation methods. Materials and methods: Fifty consecutive patients, either symptomatic and asymptomatic referring to our department in order to perform carotid endarterectomy (TEA), were enrolled. Each patient provided informed consent before undergoing CEUS. Ultrasound examination was performed using high-frequency (8–14 MHz) linear probe and a non-linear pulse inversion technique (mechanical index: 0.09–1.3). A double contrast media injection (Sonovue, 2 mL and 4 mL; Bracco, Italy) was performed. Two videotapes were recorded for every injection: early “dynamic” phase and late “flash” phase, performed with 6 high mechanical index impulses. Movies were quantitatively and qualitatively evaluated. Qualitative and quantitative evaluation were statistically compared to immunohistological diagnosis of vulnerable plaque, considered as gold standard. Results: Qualitative CEUS evaluation obtained high statistical results when compared to immunohistological results, with values of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of 94%, 68%, 87%, 85% and 86%, respectively, which became higher if considering only asymptomatic patient, with a NPV of 91%. Nevertheless, quantitative software evaluation proved less

  19. The role of contrast-enhanced ultrasound (CEUS) in visualizing atherosclerotic carotid plaque vulnerability: Which injection protocol? Which scanning technique?

    International Nuclear Information System (INIS)

    Highlights: • CEUS is a safe and efficacious technique for the identification and characterization of carotid plaque. • CEUS represents a diagnostic tool for the management of patients with carotid plaque, particularly in asymptomatic patients. • Improved diagnostic performance is achieved with the injection of 4 mL bolus of contrast-medium. • Improved diagnostic performance is achieved with the use of Dynamic Imaging rather than late-phase imaging. - Abstract: Purpose: To correlate the degree of plaque vulnerability as determined by contrast-enhanced ultrasound (CEUS) with histological findings. Secondary objectives were to optimize the CEUS acquisition technique and image evaluation methods. Materials and methods: Fifty consecutive patients, either symptomatic and asymptomatic referring to our department in order to perform carotid endarterectomy (TEA), were enrolled. Each patient provided informed consent before undergoing CEUS. Ultrasound examination was performed using high-frequency (8–14 MHz) linear probe and a non-linear pulse inversion technique (mechanical index: 0.09–1.3). A double contrast media injection (Sonovue, 2 mL and 4 mL; Bracco, Italy) was performed. Two videotapes were recorded for every injection: early “dynamic” phase and late “flash” phase, performed with 6 high mechanical index impulses. Movies were quantitatively and qualitatively evaluated. Qualitative and quantitative evaluation were statistically compared to immunohistological diagnosis of vulnerable plaque, considered as gold standard. Results: Qualitative CEUS evaluation obtained high statistical results when compared to immunohistological results, with values of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of 94%, 68%, 87%, 85% and 86%, respectively, which became higher if considering only asymptomatic patient, with a NPV of 91%. Nevertheless, quantitative software evaluation proved less

  20. Defining the non-vulnerable and vulnerable patients with computed tomography coronary angiography: evaluation of atherosclerotic plaque burden and composition.

    Science.gov (United States)

    Rodriguez-Granillo, Gaston A; Carrascosa, Patricia; Bruining, Nico; Waksman, Ron; Garcia-Garcia, Hector M

    2016-05-01

    The shift from coronary plaque stability to plaque instability remains poorly understood despite enormous efforts and expenditures have been assigned to the study of the subject. On the other hand, there have been serious advances in imaging helping us to characterizenon-vulnerable patients The latter has much more value in the clinical decision-making process since it provides high certainty that the patient's probability of a future acute event is low and treatment decisions should be made accordingly. Although coronary plaque rupture is still recognized as the main source of acute thrombotic events, numerous studies have shown that the prediction of events on an individual basis is far more complex and demands a more open approach aimed at characterizing patient risk rather than assessing the risk of thrombosis of a single plaque. Computed tomography coronary angiography (CTCA) has the ability to evaluate non-invasively the extent, burden, severity, and characteristics of coronary artery disease (CAD) and has a close relationship to intravascular ultrasound. On the basis of an excellent negative predictive value with an annualized event rate of ∼0.20% assessed over more than 6000 patients, thus providing a 5-year warranty period, CTCA has been identified as the finest non-invasive tool to exclude CAD. This means that CTCA is able to reliably characterize the non-vulnerable patient. Conversely, in the past few years, several studies have attempted to establish CTCA-derived predictors of acute coronary syndromes, both from a lesion level and a patient level basis with very low positive predictive value, thus questioning the vulnerable patient/plaque concept. PMID:26903599

  1. Selective ablation of rabbit atherosclerotic plaque with less thermal effect by the control of pulse structure of a quantum cascade laser in the 5.7 μm wavelength range

    Science.gov (United States)

    Hashimura, Keisuke; Ishii, Katsunori; Awazu, Kunio

    2016-03-01

    Cholesteryl esters are main components of atherosclerotic plaques and have an absorption peak at the wavelength of 5.75 μm originated from C=O stretching vibration mode of ester bond. Our group achieved the selective ablation of atherosclerotic lesions using a quantum cascade laser (QCL) in the 5.7 μm wavelength range. QCLs are relatively new types of semiconductor lasers that can emit mid-infrared range. They are sufficiently compact and considered to be useful for clinical application. However, large thermal effects were observed because the QCL worked as quasicontinuous wave (CW) lasers due to its short pulse interval. Then we tried macro pulse irradiation (irradiation of pulses at intervals) of the QCL and achieved effective ablation with less-thermal effects than conventional quasi-CW irradiation. However, lesion selectivity might be changed by changing pulse structure. Therefore, in this study, irradiation effects of the macro pulse irradiation to rabbit atherosclerotic plaque and normal vessel were compared. The macro pulse width and the macro pulse interval were set to 0.5 and 12 ms, respectively, because the thermal relaxation time of rabbit normal and atherosclerotic aortas in the oscillation wavelength of the QCL was 0.5-12 ms. As a result, cutting difference was achieved between rabbit atherosclerotic and normal aortas by the macro pulse irradiation. Therefore, macro pulse irradiation of a QCL in the 5.7 μm wavelength range is effective for reducing thermal effects and selective ablation of the atherosclerotic plaque. QCLs have the potential of realizing less-invasive laser angioplasty.

  2. Imaging unstable plaque.

    Science.gov (United States)

    Sriranjan, Rouchelle S; Tarkin, Jason M; Evans, Nicholas R; Chowdhury, Mohammed M; Rudd, James H

    2016-09-01

    Recent advances in imaging technology have enabled us to utilise a range of diagnostic approaches to better characterise high-risk atherosclerotic plaque. The aim of this article is to review current and emerging techniques used to detect and quantify unstable plaque in the context of large and small arterial systems and will focus on both invasive and non-invasive imaging techniques. While the diagnosis of clinically relevant atherosclerosis still relies heavily on anatomical assessment of arterial luminal stenosis, evolving multimodal cross-sectional imaging techniques that encompass novel molecular probes can provide added information with regard to plaque composition and overall disease burden. Novel molecular probes currently being developed to track precursors of plaque rupture such as inflammation, micro-calcification, hypoxia and neoangiogenesis are likely to have translational applications beyond diagnostics and have the potential to play a part in quantifying early responses to therapeutic interventions and more accurate cardiovascular risk stratification. PMID:27273430

  3. Mathematical modelling of atheroma plaque formation and development in coronary arteries

    OpenAIRE

    Cilla, Myriam; Peña, Estefanía; Martínez, Miguel A

    2014-01-01

    Atherosclerosis is a vascular disease caused by inflammation of the arterial wall, which results in the accumulation of low-density lipoprotein (LDL) cholesterol, monocytes, macrophages and fat-laden foam cells at the place of the inflammation. This process is commonly referred to as plaque formation. The evolution of the atherosclerosis disease, and in particular the influence of wall shear stress on the growth of atherosclerotic plaques, is still a poorly understood phenomenon. This work pr...

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

    Directory of Open Access Journals (Sweden)

    Yu Li

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

  5. 64Cu-DOTATATE PET/MRI for detection of activated macrophages in carotid atherosclerotic plaques

    DEFF Research Database (Denmark)

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

    2015-01-01

    selected markers of plaque vulnerability using real-time quantitative polymerase chain reaction. These results were compared with in vivo 64Cu-DOTATATE uptake calculated as the mean standardized uptake value. Univariate analysis of real-time quantitative polymerase chain reaction and PET showed that...... cluster of differentiation 163 (CD163) and CD68 gene expression correlated significantly but weakly with mean standardized uptake value in scans performed 85 minutes post injection (P<0.001 and P=0.015, respectively). Subsequent multivariate analysis showed that CD163 correlated independently with 64Cu...

  6. Development of Tc-99m Imaging Agents for Abeta Plaques

    International Nuclear Information System (INIS)

    Development of SPECT imaging agents based on Tc-99m targeting Aβ plaques is useful for diagnosis of Alzheimer's disease (AD). A stilbene derivative, [11C]SB-13, showing promise in detecting senile plaques present in AD patients has been reported previously. Based on the 4(prime)-amino-stilbene core structure we have added substituted groups through which a chelating group, N2S2, was conjugated. We report herein a series of Tc-99m labeled stilbene derivative conjugated with a TcO[N2S2] core. The syntheses of stilbenes containing a N2S2 chelating ligand are achieved by a scheme shown. Lipophilic 99mTc stilbene complexes were successfully prepared and purified through HPLC. Preliminary results of in vitro labeling of brain sections from transgenic mice showed very promising plaque labeling. These 99mTc stilbene derivatives are warranted for further evaluations as potential imaging agents targeting amyloid plaques.

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

    Science.gov (United States)

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

    2016-07-01

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

  8. CAROTID ATHEROSCLEROTIC LESION IN YOUNG PATIENTS

    Directory of Open Access Journals (Sweden)

    N. V. Pizova

    2014-01-01

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

  9. High-resolution black-blood MRI findings of carotid atherosclerotic plaque in initial and recurrent acute ischemic stroke: a comparison study

    International Nuclear Information System (INIS)

    Objective: To investigate MR imaging characteristics of carotid plaque in patients with first-time and recurrent acute ischemic stroke. Methods: During the period from Aug. 2009 to Nov. 2010, high-resolution black-blood MR scanning of carotid was carried out in 89 patients with recently-developed acute ischemic stroke, which included initial attack (n=51) and recurrent attack (n=38). The ipsilateral responsible carotid arteries were quantitatively and qualitatively analyzed. The carotid plaque burden and compositional features were compared between the initial and recurrent stroke patients. Results: Of the 89 patients, 51 had first-time stroke and 38 had recurrent stroke. The mean WA, WT and PWV were greater in patients with recurrent stroke than those in patients with first-time stroke (P<0.05). Compared with the first- time stroke patients, the recurrent stroke patients had significantly higher prevalence of calcification (44.7% versus 23.5%, P=0.035) and larger volume of LRNC as well (179.14±254.81 mm2 versus 71.65± 111.15 mm2, P=0.027). IPH and/or fibrous cap rupture were observed in 15.8% of patients with recurrent stroke and only 3.9% of patients with first-time stroke. Conclusion: Carotid plaques in patients with recurrent ischemic stroke are significantly worse than those in patients with first-time stroke. Monitoring the carotid plaques in patients with initial stroke by MR scanning may be helpful for the prevention of recurrent stroke. (authors)

  10. Modeling of drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls to treat vulnerable plaques

    KAUST Repository

    Hossain, Shaolie S.

    2010-01-01

    The main objective of this work is to develop computational tools to support the design of a catheter-based local drug delivery system that uses nanoparticles as drug carriers in order to treat vulnerable plaques and diffuse atherosclerotic disease.

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

    Directory of Open Access Journals (Sweden)

    Ricardo A Garcia

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

  12. On the potential of a new IVUS elasticity modulus imaging approach for detecting vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study

    Energy Technology Data Exchange (ETDEWEB)

    Floc' h, Simon Le; Tracqui, Philippe; Ohayon, Jacques [Laboratory TIMC-DynaCell, UJF, CNRS UMR 5525, In3S, Grenoble (France); Cloutier, Guy [Laboratory of Biorheology and Medical Ultrasonics, Research Center, University of Montreal Hospital (CRCHUM), Montreal, Quebec (Canada); Finet, Gerard [Department of Hemodynamics and Interventional Cardiology, Hospices Civils de Lyon and Claude Bernard University Lyon 1, INSERM Unit 886, Lyon (France); Pettigrew, Roderic I, E-mail: Guy.Cloutier@umontreal.c, E-mail: Jacques.Ohayon@imag.f [Laboratory of Integrative Cardiovascular Imaging Science, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States)

    2010-10-07

    Peak cap stress amplitude is recognized as a good indicator of vulnerable plaque (VP) rupture. However, such stress evaluation strongly relies on a precise, but still lacking, knowledge of the mechanical properties exhibited by the plaque components. As a first response to this limitation, our group recently developed, in a previous theoretical study, an original approach, called iMOD (imaging modulography), which reconstructs elasticity maps (or modulograms) of atheroma plaques from the estimation of strain fields. In the present in vitro experimental study, conducted on polyvinyl alcohol cryogel arterial phantoms, we investigate the benefit of coupling the iMOD procedure with the acquisition of intravascular ultrasound (IVUS) measurements for detection of VP. Our results show that the combined iMOD-IVUS strategy: (1) successfully detected and quantified soft inclusion contours with high positive predictive and sensitivity values of 89.7 {+-} 3.9% and 81.5 {+-} 8.8%, respectively, (2) estimated reasonably cap thicknesses larger than {approx}300 {mu}m, but underestimated thinner caps, and (3) quantified satisfactorily Young's modulus of hard medium (mean value of 109.7 {+-} 23.7 kPa instead of 145.4 {+-} 31.8 kPa), but overestimated the stiffness of soft inclusions (mean Young's moduli of 31.4 {+-} 9.7 kPa instead of 17.6 {+-} 3.4 kPa). All together, these results demonstrate a promising benefit of the new iMOD-IVUS clinical imaging method for in vivo VP detection.

  13. On the potential of a new IVUS elasticity modulus imaging approach for detecting vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study

    International Nuclear Information System (INIS)

    Peak cap stress amplitude is recognized as a good indicator of vulnerable plaque (VP) rupture. However, such stress evaluation strongly relies on a precise, but still lacking, knowledge of the mechanical properties exhibited by the plaque components. As a first response to this limitation, our group recently developed, in a previous theoretical study, an original approach, called iMOD (imaging modulography), which reconstructs elasticity maps (or modulograms) of atheroma plaques from the estimation of strain fields. In the present in vitro experimental study, conducted on polyvinyl alcohol cryogel arterial phantoms, we investigate the benefit of coupling the iMOD procedure with the acquisition of intravascular ultrasound (IVUS) measurements for detection of VP. Our results show that the combined iMOD-IVUS strategy: (1) successfully detected and quantified soft inclusion contours with high positive predictive and sensitivity values of 89.7 ± 3.9% and 81.5 ± 8.8%, respectively, (2) estimated reasonably cap thicknesses larger than ∼300 μm, but underestimated thinner caps, and (3) quantified satisfactorily Young's modulus of hard medium (mean value of 109.7 ± 23.7 kPa instead of 145.4 ± 31.8 kPa), but overestimated the stiffness of soft inclusions (mean Young's moduli of 31.4 ± 9.7 kPa instead of 17.6 ± 3.4 kPa). All together, these results demonstrate a promising benefit of the new iMOD-IVUS clinical imaging method for in vivo VP detection.

  14. Inflammation, plaque progression and vulnerability: evidence from intravascular ultrasound imaging

    OpenAIRE

    Kataoka, Yu; Puri, Rishi; Nicholls, Stephen J.

    2015-01-01

    Increasing evidence points to a critical role of inflammation in the development and propagation of atherosclerotic cardiovascular disease. Pathological studies in human and animal models have elucidated specific inflammatory mediators contributing to the progression and rupture of atherosclerotic plaque in the artery wall. These observations not only outline the importance of inflammation in atheroma progression but also the potential of anti-inflammatory therapeutic approaches to prevent an...

  15. Dendritic Cells Expressing Triggering Receptor Expressed on Myeloid Cells-1 Correlate with Plaque Stability in Symptomatic and Asymptomatic Patients with Carotid Stenosis

    Science.gov (United States)

    Shao, Zhifei; Agrawal, Devendra K.

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory cells, including T-lymphocytes, dendritic cells (DCs) and macrophages that are responsible for progression and destabilization of atherosclerotic plaques. Stressed cells undergoing necrosis release molecules that act as endogenous danger signals to alert and activate innate immune cells. In atherosclerotic tissue the number of DCs increases with the progression of the lesion and produce several inflammatory cytokines and growth factors. Triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role in inflammation. However, relationship of DCs and the role of TREM-1 with the stability of atherosclerotic plaques have not been examined. In this study, we investigated the heterogeneity of the plaque DCs, myeloid (mDC1 and mDC2) and plasmacytoid (pDCs), and examined the expression of TREM-1 and their co-localization with DCs in the plaques from symptomatic (S) and asymptomatic (AS) patients with carotid stenosis. We found increased expression of HLA-DR, fascin, and TREM-1 and decreased expression of TREM-2 and α-smooth muscle actin in S compared to AS atherosclerotic carotid plaques. Both TREM-1 and fascin were co-localized suggesting increased expression of TREM-1 in plaque DCs of S compared to AS patients. These data were supported by increased mRNA transcripts of TREM-1 and decreased mRNA transcripts of TREM-2 in carotid plaques of S compared to AS patients. There was higher density of both CD1c+ mDC1 and CD141+ mDC2 in the carotid plaques from AS compared to S patients, where as the density of CD303+ pDCs were higher in the carotid plaques of S compared to AS patients. These findings suggest a potential role of pDCs and TREM-1 in atherosclerotic plaque vulnerability. Thus, newer therapies could be developed to selectively block TREM-1 for stabilizing atherosclerotic plaques. PMID:27148736

  16. Ultrasound features of human carotid plaques

    OpenAIRE

    Östling, Gerd

    2013-01-01

    Atherosclerotic plaques in the carotid arteries are common in a middle-aged population. When a carotid plaque ruptures it may result in a cerebrovascular event. However, only a minor part of carotid plaques will eventually rupture. Finding those plaques is essential to decide the most appropriate treatment strategy. With non-invasive ultrasound the carotid plaques can be visualized for assessment of various features. Plaques that appear dark on the ultrasound image, i.e. echolucent plaques...

  17. Carotid plaque, intima-media thickness, and incident aortic stenosis

    DEFF Research Database (Denmark)

    Martinsson, Andreas; Östling, Gerd; Persson, Margaretha;

    2014-01-01

    OBJECTIVE: Aortic stenosis (AS) shares risk factors with atherosclerotic vascular disease. Carotid intima-media thickness (IMT) and plaque may reflect the cumulative damage from exposure to different atherosclerotic risk factors. We examined the relationship of carotid IMT and plaque with incident...... risk factors for incident AS were studied in age- and sex-adjusted and expanded multivariable-adjusted Cox regression models. A total of 69 (1.4%) participants developed AS during up to 20 years of follow-up. Significant risk factors for AS in age- and sex-adjusted analyses were (P<0.05) body mass...

  18. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

  19. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    International Nuclear Information System (INIS)

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

  20. In vivo and in vitro evidence that 99mTc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery

    International Nuclear Information System (INIS)

    Recent advances in basic science have established that inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Inflammatory cells are thought to be responsible for the transformation of a stable plaque into a vulnerable one. Lymphocytes constitute at least 20 % of infiltrating cells in these vulnerable plaques. Therefore, the interleukin-2 (IL-2) receptor, being overexpressed on activated T lymphocytes, may represent an attractive biomarker for plaque vulnerability. The aim of this study was to evaluate the specificity of radiolabelled IL-2 [99mTc-hydrazinonicotinamide (HYNIC)-IL-2] for imaging the lymphocytic infiltration in carotid plaques in vivo by planar and single photon emission computed tomography (SPECT)/CT imaging and ex vivo by microSPECT and autoradiography. For the in vivo study, ten symptomatic patients with advanced plaques at ultrasound who were scheduled for carotid endarterectomy underwent 99mTc-HYNIC-IL-2 scintigraphy. The images were analysed visually on planar and SPECT images and semi-quantitatively on SPECT images by calculating target to background (T/B) ratios. After endarterectomy, immunomorphological evaluation and immunophenotyping were performed on plaque slices. For the ex vivo studies, four additional patients were included and, after in vitro incubation of removed plaques with 99mTc-HYNIC-IL-2, autoradiography was performed and microSPECT images were acquired. Visual analysis defined clear 99mTc-HYNIC-IL-2 uptake in seven of the ten symptomatic plaques. SPECT/CT allowed visualization in eight of ten. A significant correlation was found between the number of CD25+ lymphocytes and the total number of CD25+ cells in the plaque and the T/B ratio with adjacent carotid artery as background (Pearson's r = 0.89, p = 0.003 and r = 0.87, p = 0.005, respectively). MicroSPECT imaging showed clear 99mTc-HYNIC-IL-2 uptake within the plaque wall and not in the lipidic core. With autoradiography, only CD3+ lymphocytes were found to

  1. Early characterization of atherosclerotic coronary plaques with multidetector computed tomography in patients with acute coronary syndrome. A comparative study with intravascular ultrasound

    International Nuclear Information System (INIS)

    We compared 16-slice computed tomography (CT) with intravascular ultrasound (IVUS) in their ability to identify the culprit lesion, and to assess plaque characterization and vascular remodelling in acute coronary syndrome (ACS). Twenty patients were prospectively studied. Coronary plaque identification and characterization were compared using 16-slice CT and 40-MHz catheter-based IVUS. Minimum lumen area (MLA), cross-sectional vessel area (CVA) and vessel remodelling were determined for each comparable lesion. One hundred and sixty-nine segments were compared and 84 plaques analysed. Sixteen-slice CT detected 95% of culprit lesions (19/20). No feature suggestive of plaque rupture was detected by 16-slice CT. Attenuation measurements within all lesions revealed different values for hypoechoic (38 ± 33 HU), hyperechoic (94 ± 44 HU), and calcified plaques (561 ± 216 HU), (P < 0.001). Agreement between 16-slice CT and IVUS on measuring MLA and CVA was evaluated using Bland-Altman analysis. Pearson and intra-class coefficient (ICC) were 0.81 and 0.70 for MLA, and 0.81 and 0.36 for CVA, for 16-slice CT and IVUS, respectively. Agreement between both techniques for vessel positive remodelling was moderate (kappa 0.54, P < 0.001). Sixteen-slice CT has shown moderate accuracy in quantifying and characterizing coronary plaques compared with IVUS. Spatial resolution of 16-slice CT remains a major limitation, however, to accurately assess the complex lesions involved in ACS. (orig.)

  2. Early characterization of atherosclerotic coronary plaques with multidetector computed tomography in patients with acute coronary syndrome. A comparative study with intravascular ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Iriart, Xavier; Dos-Santos, Pierre [Universite Bordeaux 2, Inserm U. 441 Atherosclerose, Bordeaux (France); Brunot, Sebastien [CHU de Bordeaux, Hopital du Haut-Leveque, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France); Unite de Soins Intensifs Cardiologiques, Pessac (France); Unite d' Imagerie Thoracique et Cardiovasculaire, Hopital Cardiologique, Pessac (France); Coste, Pierre; Leroux, Lionel [Universite Bordeaux 2, Inserm U. 441 Atherosclerose, Bordeaux (France); Unite de Soins Intensifs Cardiologiques, Pessac (France); Montaudon, Michel [Universite Bordeaux 2, Inserm U. 885 F 33076, Bordeaux (France); CHU de Bordeaux, Hopital du Haut-Leveque, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France); Labeque, Jean-Noel; Jais, Catherine [Unite de Soins Intensifs Cardiologiques, Pessac (France); Laurent, Francois [Universite Bordeaux 2, Inserm U. 885 F 33076, Bordeaux (France); CHU de Bordeaux, Hopital du Haut-Leveque, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France); Unite d' Imagerie Thoracique et Cardiovasculaire, Hopital Cardiologique, Pessac (France)

    2007-10-15

    We compared 16-slice computed tomography (CT) with intravascular ultrasound (IVUS) in their ability to identify the culprit lesion, and to assess plaque characterization and vascular remodelling in acute coronary syndrome (ACS). Twenty patients were prospectively studied. Coronary plaque identification and characterization were compared using 16-slice CT and 40-MHz catheter-based IVUS. Minimum lumen area (MLA), cross-sectional vessel area (CVA) and vessel remodelling were determined for each comparable lesion. One hundred and sixty-nine segments were compared and 84 plaques analysed. Sixteen-slice CT detected 95% of culprit lesions (19/20). No feature suggestive of plaque rupture was detected by 16-slice CT. Attenuation measurements within all lesions revealed different values for hypoechoic (38 {+-} 33 HU), hyperechoic (94 {+-} 44 HU), and calcified plaques (561 {+-} 216 HU), (P < 0.001). Agreement between 16-slice CT and IVUS on measuring MLA and CVA was evaluated using Bland-Altman analysis. Pearson and intra-class coefficient (ICC) were 0.81 and 0.70 for MLA, and 0.81 and 0.36 for CVA, for 16-slice CT and IVUS, respectively. Agreement between both techniques for vessel positive remodelling was moderate (kappa = 0.54, P < 0.001). Sixteen-slice CT has shown moderate accuracy in quantifying and characterizing coronary plaques compared with IVUS. Spatial resolution of 16-slice CT remains a major limitation, however, to accurately assess the complex lesions involved in ACS. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Rosa Sessa

    2013-07-01

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

  4. Inestabilidad en múltiples placas ateroescleróticas en pacientes fallecidos por infarto agudo de miocardio Instability in multiple atherosclerotic plaques in patients who died of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Ricardo A. Sarmiento

    2011-08-01

    Full Text Available Los procesos inflamatorios en los síndromes coronarios agudos juegan un rol importante en la inestabilidad de la placa ateroesclerótica. Nuestro objetivo fue evaluar la presencia y distribución de placas vulnerables e infiltrados inflamatorios en pacientes fallecidos por infarto agudo de miocardio y su comparación con los hallazgos en pacientes fallecidos por cuadros no coronarios. Se analizaron los estudios anatomopatológicos de corazón de 68 pacientes fallecidos por infarto agudo de miocardio y 15 fallecidos por causa no coronaria. Se registró la presencia de trombo, hemorragia intraplaca, ruptura endotelial e infiltrado inflamatorio. Al evaluar los pacientes fallecidos por IAM, encontramos trombo en 73.5% de las arterias responsables del IAM y en 28.7% de las no responsables (p In acute coronary syndromes inflammatory process plays an important role in atherosclerotic plaque instability. Our aim was to evaluate the presence and distribution of vulnerable plaques and inflammatory infiltrates in patients who died of acute myocardial infarction in comparison to patients who died of non-coronary heart disease. We analyzed pathologic studies of the heart of 68 patients who died of acute myocardial infarction and 15 patients who died of non-coronary heart disease. The presence of thrombus, intraplaque hemorrhage, endothelial rupture and inflammatory infiltrates were registered. In patients who died of myocardial infarction, we found thrombus in 73.5% of the involved arteries and in 28.7% of the non involved (p < 0.0001. Intraplaque hemorrhage was found in 70.5% of involved arteries and in 39.7% of the non involved (p < 0.0001; endothelial rupture in 29.4% of involved arteries and in 3.7% of non involved arteries (p < 0.0001. There was no difference in the presence of inflammatory infiltrates (76.5% versus 68.4%. Comparing with patients whoo have died of non-coronary heart disease, the presence of thrombus was significantly higher (73.5% vs

  5. 胆固醇结晶激活动脉粥样硬化斑块巨噬细胞NLRP3炎症体的途径%The Ways of Cholesterol Crystals Activate the Atherosclerotic Plaque Macrophages NLRP3 Inflammasome

    Institute of Scientific and Technical Information of China (English)

    孟玲丽; 姚剑挺; 田野; 旦菊花

    2015-01-01

    动脉粥样硬化既是胆固醇在血管壁聚集的疾病,也是发生在动脉壁的一种低强度慢性炎症形式.近年来有研究证实胆固醇结晶在动脉粥样硬化发生发展中具有重要作用.新的显微技术证实,胆固醇结晶在动脉粥样硬化斑块形成的早期即已出现,并与早期炎症有关.胆固醇结晶通过诱发局部炎症,促进大的脂质核心形成;刺破纤维帽,导致斑块破裂进而促进动脉粥样硬化斑块的进展.在影响斑块进程中,NLRP3炎症体的激活对此发挥了重要的作用.NLRP3炎症体是研究最多最明确的炎症体,其与非炎症性疾病的发生发展密切相关.以胆固醇结晶激活NLRP3炎症体的途径作为研究靶点,为动脉粥样硬化的诊断和治疗提供了新的思路和方法.该文就胆固醇结晶在动脉粥样硬化斑块中激活巨噬细胞NLRP3炎症体的两种途径做一综述.%Atherosclerosis is a disease of aggregation of cholesterol in the vessel wall,and also a low-intensity chronic inflammation form that occurs in the artery wall.In recent years,some researches have shown that cholesterol crystals play an important role on atherosclerosis development.New microscopy technology confirmed that cholesterol crystals had emerged in the early atherosclerotic plaque formation,which related with early inflammatory.Cholesterol crystals induce local inflammation,and promote the formation of large lipid core; pierce the fibrous cap,leading to plaque rupture thereby promoting the atherosclerotic plaque development.During the process of impacting plaques,NLRP3 inflammasome activation plays a critical part for it.NLRP3 inflammasome is the up most explicit inflammasome,closely related to the development of non-inflammatory diseases.Cholesterol crystals activating the NLRP3 inflammasome pathway is considered as one possible research target,providing new ideas and methods for the diagnosis and treatment of atherosclerosis.This article is aimed to

  6. Identification of periodontal pathogens in atherosclerotic vessels

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  7. The development and potential of acoustic radiation force impulse (ARFI) imaging for carotid artery plaque characterization.

    Science.gov (United States)

    Allen, Jason D; Ham, Katherine L; Dumont, Douglas M; Sileshi, Bantayehu; Trahey, Gregg E; Dahl, Jeremy J

    2011-08-01

    Stroke is the third leading cause of death and long-term disability in the USA. Currently, surgical intervention decisions in asymptomatic patients are based upon the degree of carotid artery stenosis. While there is a clear benefit of endarterectomy for patients with severe (> 70%) stenosis, in those with high/moderate (50-69%) stenosis the evidence is less clear. Evidence suggests ischemic stroke is associated less with calcified and fibrous plaques than with those containing softer tissue, especially when accompanied by a thin fibrous cap. A reliable mechanism for the identification of individuals with atherosclerotic plaques which confer the highest risk for stroke is fundamental to the selection of patients for vascular interventions. Acoustic radiation force impulse (ARFI) imaging is a new ultrasonic-based imaging method that characterizes the mechanical properties of tissue by measuring displacement resulting from the application of acoustic radiation force. These displacements provide information about the local stiffness of tissue and can differentiate between soft and hard areas. Because arterial walls, soft tissue, atheromas, and calcifications have a wide range in their stiffness properties, they represent excellent candidates for ARFI imaging. We present information from early phantom experiments and excised human limb studies to in vivo carotid artery scans and provide evidence for the ability of ARFI to provide high-quality images which highlight mechanical differences in tissue stiffness not readily apparent in matched B-mode images. This allows ARFI to identify soft from hard plaques and differentiate characteristics associated with plaque vulnerability or stability. PMID:21447606

  8. In vivo and in vitro evidence that Tc-99m-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery

    NARCIS (Netherlands)

    Glaudemans, Andor W. J. M.; Bonanno, Elena; Galli, Filippo; Zeebregts, Clark J.; de Vries, Erik; Koole, Michel; Luurtsema, Gert; Boersma, Hendrikus H.; Taurino, Maurizio; Slart, Riemer H. J. A.; Signore, Alberto

    2014-01-01

    Purpose Recent advances in basic science have established that inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Inflammatory cells are thought to be responsible for the transformation of a stable plaque into a vulnerable one. Lymphocytes constitute at least 20 % of infiltrat

  9. Current status of vulnerable plaque detection.

    LENUS (Irish Health Repository)

    Sharif, Faisal

    2012-02-01

    Critical coronary stenoses have been shown to contribute to only a minority of acute coronary syndromes (ACS) and sudden cardiac death. Autopsy studies have identified a subgroup of high-risk patients with disrupted vulnerable plaque and modest stenosis. Consequently, a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease. Recent advances in invasive and noninvasive imaging techniques have shown the potential to identify these high-risk plaques. The anatomical characteristics of the vulnerable plaque such as thin cap fibroatheroma and lipid pool can be identified with angioscopy, high frequency intravascular ultrasound, intravascular MRI, and optical coherence tomography. Efforts have also been made to recognize active inflammation in high-risk plaques using intravascular thermography. Plaque chemical composition by measuring electromagnetic radiation using spectroscopy is also an emerging technology to detect vulnerable plaques. Noninvasive imaging with MRI, CT, and PET also holds the potential to differentiate between low and high-risk plaques. However, at present none of these imaging modalities are able to detect vulnerable plaque neither has been shown to definitively predict outcome. Nevertheless in contrast, there has been a parallel development in the physiological assessment of advanced atherosclerotic coronary artery disease. Thus recent trials using fractional flow reserve in patients with modest non flow-limiting stenoses have shown that deferral of PCI with optimal medical therapy in these patients is superior to coronary intervention. Further trials are needed to provide more information regarding the natural history of high-risk but non flow-limiting plaque to establish patient-specific targeted therapy and to refine plaque stabilizing strategies in the future.

  10. Non-invasive in vivo characterization of human carotid plaques with acoustic radiation force impulse ultrasound: comparison with histology after endarterectomy.

    Science.gov (United States)

    Czernuszewicz, Tomasz J; Homeister, Jonathon W; Caughey, Melissa C; Farber, Mark A; Fulton, Joseph J; Ford, Peter F; Marston, William A; Vallabhaneni, Raghuveer; Nichols, Timothy C; Gallippi, Caterina M

    2015-03-01

    Ischemic stroke from thromboembolic sources is linked to carotid artery atherosclerotic disease with a trend toward medical management in asymptomatic patients. Extent of disease is currently diagnosed by non-invasive imaging techniques that measure luminal stenosis, but it has been suggested that a better biomarker for determining risk of future thromboembolic events is plaque morphology and composition. Specifically, plaques that are composed of mechanically soft lipid/necrotic regions covered by thin fibrous caps are the most vulnerable to rupture. An ultrasound technique that non-invasively interrogates the mechanical properties of soft tissue, called acoustic radiation force impulse (ARFI) imaging, has been developed as a new modality for atherosclerotic plaque characterization using phantoms and atherosclerotic pigs, but the technique has yet to be validated in vivo in humans. In this preliminary study, in vivo ARFI imaging is presented in a case study format for four patients undergoing clinically indicated carotid endarterectomy and compared with histology. In two type Va plaques, characterized by lipid/necrotic cores covered by fibrous caps, mean ARFI displacements in focal regions were high relative to the surrounding plaque material, suggesting soft features were covered by stiffer layers within the plaques. In two type Vb plaques, characterized by heavy calcification, mean ARFI peak displacements were low relative to the surrounding plaque and arterial wall, suggesting stiff tissue. This pilot study illustrates the feasibility and challenges of transcutaneous ARFI for characterizing the material and structural composition of carotid atherosclerotic plaques via mechanical properties, in humans, in vivo. PMID:25619778

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

    Directory of Open Access Journals (Sweden)

    Tang Bing

    2011-04-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  13. Carotid and cerebrovascular disease in symptomatic patients with type 2 diabetes: assessment of prevalence and plaque morphology by dual-source computed tomography angiography

    OpenAIRE

    Deng Wen; Shao Heng; Dong Zhi-hui; Chu Zhi-gang; Yang Zhi-gang; He Ci; Chen Jing; Peng Li-qing; Tang Si-shi; Xiao Jia-he

    2010-01-01

    Abstract Background Plaque morphology directly correlates with risk of embolism and the recently developed dual-source computed tomography angiography (DSCTA) may help to detect plaques more precisely. The aim of our study was to evaluate the prevalence and morphology of carotid and cerebrovascular atherosclerotic plaques in patients with symptomatic type 2 diabetes mellitus (DM) by DSCTA. Methods From July 2009 to August 2010, DSCTA was prospectively performed in 125 consecutive patients wit...

  14. Image Analysis for Contrast Enhanced Ultrasound Carotid Plaque Imaging

    NARCIS (Netherlands)

    Z. Akkus (Zeynettin)

    2014-01-01

    markdownabstract__Abstract__ Intraplaque neovascularization (IPN) has been presented as an important biomarker for progressive atherosclerotic disease and plaque vulnerability in several pathological studies. Therefore, quantification of IPN may allow early prediction of plaque at risk of rupture a

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    cholesterol, inflammatory cytokines and markers (interleukin-6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase, MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells. RESULTS: High...... fat feeding resulted in marked increases in body mass and plasma lipid levels. Dietary TEMPOL decreased both parameters. In the high-fat-fed mice significant elevations in plasma lipid levels and the inflammatory markers IL-6, MCP-1, MPO, SAA were detected, along with an increase in leptin and a......OBJECTIVE: The nitroxide compound TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl radical) has been shown to prevent obesity-induced changes in adipokines in cell and animal systems. In this study we investigated whether supplementation with TEMPOL inhibits inflammation and atherosclerosis...

  16. Blue-Green Algae Inhibit the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice.

    Science.gov (United States)

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Wegner, Casey J; Park, Young-Ki; Balunas, Marcy; Lee, Ji-Young

    2015-12-01

    Hyperlipidemia and inflammation contribute to the development of atherosclerotic lesions. Our objective was to determine antiatherogenic effect of edible blue-green algae (BGA) species, that is, Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), in apolipoprotein E knockout (ApoE(-/-)) mice, a well-established mouse model of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat/high-cholesterol (HF/HC, 15% fat and 0.2% cholesterol by wt) control diet or a HF/HC diet supplemented with 5% (w/w) of NO or SP powder for 12 weeks. Plasma total cholesterol (TC) and triglycerides (TG) were measured, and livers were analyzed for histology and gene expression. Morphometric analysis for lesions and immunohistochemical analysis for CD68 were conducted in the aorta and the aortic root. NO supplementation significantly decreased plasma TC and TG, and liver TC, compared to control and SP groups. In the livers of NO-fed mice, less lipid droplets were present with a concomitant decrease in fatty acid synthase protein levels than the other groups. There was a significant increase in hepatic low-density lipoprotein receptor protein levels in SP-supplemented mice than in control and NO groups. Quantification of aortic lesions by en face analysis demonstrated that both NO and SP decreased aortic lesion development to a similar degree compared with control. While lesions in the aortic root were not significantly different between groups, the CD68-stained area in the aortic root was significantly lowered in BGA-fed mice than controls. In conclusion, both NO and SP supplementation decreased the development of atherosclerotic lesions, suggesting that they may be used as a natural product for atheroprotection. PMID:26566121

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

    International Nuclear Information System (INIS)

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

  18. Importance of atherosclerotic stenotic lesion of the brachiocephalic arteries in the development of cognitive impairments

    Directory of Open Access Journals (Sweden)

    D. R. Khasanova

    2015-03-01

    Full Text Available The impact of the pattern of atherosclerotic stenotic lesion on the clinical presentation of cognitive impairments (CIs has been inadequately investigated. Objective: to estimate the impact of the degree and site of an atherosclerotic stenotic process on cerebral perfusion and cognitive functions. Patients and methods. A total of 123 patients (65 men and 58 women aged 50 to 75 years with brachiocephalic artery stenosis of at least 40%, without hypertension, diabetes mellitus, or other systemic vascular pathology were examined. The structural state of the brain substance and the state of cerebral blood flow were evaluated by magnetic resonance imaging and magnetic resonance angiography. The scale described by P. Scheltens et al. was used to determine changes in the white matter. The site and degree of a stenotic process were estimated by extracranial and transcranial duplex scanning. CIs were identified applying a set of neuropsychological assessment scales. The Hamilton hospital depression rating scale was also employed. Results and discussion. Varying degrees of CIs were detected in the majority of the examinees with brachiocephalic artery atherosclerosis. The most severe CIs were associated with the involvement of parietal and frontal lobes. There was significant deterioration in cognitive functions with a higher percentage of stenosis: more severe CIs were seen in the presence of stenosis in the carotid system than in those in the vertebrobasilar bed. In addition, the patients with concomitant stenoses and tandem stenoses were observed to have more pronounced CIs than those with single artery stenosis. Cerebral atherosclerosis is shown to be one of the major risk factors for CIs. Not only the degree of stenoses, but also to a greater extent their site was observed to impact the occurrence of CIs accompanied by the development of a perfusion deficit in the specific vascular beds. The determination of the pattern of a stenotic process will be

  19. Saliva as the Sole Nutritional Source in the Development of Multispecies Communities in Dental Plaque.

    Science.gov (United States)

    Jakubovics, Nicholas S

    2015-06-01

    Dental plaque is a polymicrobial biofilm that forms on the surfaces of teeth and, if inadequately controlled, can lead to dental caries or periodontitis. Nutrient availability is the fundamental limiting factor for the formation of dental plaque, and for its ability to generate acid and erode dental enamel. Nutrient availability is also critical for bacteria to grow in subgingival biofilms and to initiate periodontitis. Over the early stages of dental plaque formation, micro-organisms acquire nutrients by breaking down complex salivary substrates such as mucins and other glycoproteins. Once dental plaque matures, dietary carbohydrates become more important for supragingival dental plaque, and gingival crevicular fluid forms the major nutrient source for subgingival microorganisms. Many species of oral bacteria do not grow in laboratory monocultures when saliva is the sole nutrient source, and it is now clear that intermicrobial interactions are critical for the development of dental plaque. This chapter aims to provide an overview of the key metabolic requirements of some well-characterized oral bacteria, and the nutrient webs that promote the growth of multispecies communities and underpin the pathogenicity of dental plaque for both dental caries and periodontitis. PMID:26185065

  20. Relationship between the characteristics of atherosclerotic plaque of carotid artery and cardiovascular events in a senior cohort of Renqiu region,Hebei%河北省任丘市城乡老年居民颈动脉斑块特征与心脑血管事件的相关性研究

    Institute of Scientific and Technical Information of China (English)

    张广波; 于凯; 冀瑞俊; 王拥军; 高素颖; 颜应琳

    2016-01-01

    new onset cardiovascular and cerebrovascular events as dependent variable,the single factor analysis showed that the carotid plaques(χ2 =14.969,P <0.001 ),and the multiple plaque(χ2 =22.509,P <0.001 ),the carotid artery stenosis (χ2 =27.561,P <0.001),the homogeneous plaque(χ2 =4.606,P <0.050),the non -homogeneous plaque(χ2 =18.301,P <0.001),the history of hypertension(χ2 =33.709,P <0.001),the high blood fat disease(χ2 =11.262, P <0.001),and the history of diabetes(χ2 =5.525,P <0.050),the coronary heart disease history(χ2 =10.440, P <0.001),the gender(χ2 =5.606,P <0.050),the smoking(χ2 =4.823,P <0.050)and the systolic blood pressure value,were all associated with the new cardio cerebral vascular events.Multivariate analysis showed that,the heterogeneous plaque(β=0.371,P <0.050),the carotid artery stenosis(β=0.621,P <0.050),the history of hypertension(β=0.517,P <0.001)and smoking(β=0.264,P <0.050)were shown to be significantly associates with new onset cardiovascular events.Conclusion The characteristics of atherosclerotic plaque of carotid artery were significantly associated with the subsequent cardiovascular events among 60 -70 years old residence in Renqiu region,Hebei.Routine carotid ultrasound screening might be useful for identify those people with high risk of develo-ping cardiovascular events.%目的:了解河北省任丘市城乡老年居民颈动脉斑块特征与新发心脑血管事件的关系。方法经随机整群抽样法,以河北省任丘市年龄60~70岁的常住居民为筛查对象,进行面对面健康问卷调查、颈部血管超声检查,共筛查4413例,其中男性1876例,女性2537例,利用超声检测受检者颈动脉斑块、狭窄的发生情况。根据颈动脉斑块的回声、有无狭窄将颈动脉斑块分为有无斑块、有无狭窄、单发与多发、均质与不均质斑块,分析颈动脉斑块特征与新发心脑血管事件的关系。结果4413例中,颈动脉无斑块1975例(44

  1. Effect of atorvastatin on expression of macrophage and smooth muscle actin in carotid atherosclerotic plaques in rabbits%阿托伐他汀对家兔颈动脉粥样硬化斑块内巨噬细胞浸润和平滑肌肌动蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    于熙滢; 曹海利; 刘雅君; 刘洋; 李晓光; 班翔; 魏林

    2011-01-01

    slices were obtained.Blood lipids and lipoproteins were detected and the development of atherosclerotic plaques was evaluated by light microscopy.The levels of macrophages and smooth muscle actin in the common carotid artery were measured by immunohistochemical analysis.RESULTS: Serum concentrations of TC and LDL-C in atorvastatin group were lower than those in hypercholesterolemia model group (P <0.01 ).The intimal-medial thickness [(0.49 ±0.072) mm vs.(0.66 ±0.079) mm, P <0.05]in atorvastatin group was significantly less than that in hypercholesterolemia model group.Immunohistochemical analysis showed much less stain in macrophages in atorvastatin group compared with that in hypercholesterolemia model group.More smooth muscle actin was observed in atherosclerotic plaque than that in atorvastatin group.CONCLUSIONS: Atorvastatin may decrease the level of macrophages in atherosclerotic plaque and increase the development of smooth muscle actin, thus prohibiting the formation and development of atherosclerosis.

  2. Ursodeoxycholic acid impairs atherogenesis and promotes plaque regression by cholesterol crystal dissolution in mice.

    Science.gov (United States)

    Bode, Niklas; Grebe, Alena; Kerksiek, Anja; Lütjohann, Dieter; Werner, Nikos; Nickenig, Georg; Latz, Eicke; Zimmer, Sebastian

    2016-09-01

    Atherosclerosis is a chronic inflammatory disease driven primarily by a continuous retention of cholesterol within the subendothelial space where it precipitates to form cholesterol crystals (CC). These CC trigger a complex inflammatory response through activation of the NLRP3 inflammasome and promote lesion development. Here we examined whether increasing cholesterol solubility with ursodeoxycholic acid (UDCA) affects vascular CC formation and ultimately atherosclerotic lesion development. UDCA mediated intracellular CC dissolution in macrophages and reduced IL-1β production. In ApoE(-/-) mice, UDCA treatment not only impaired atherosclerotic plaque development but also mediated regression of established vascular lesions. Importantly, mice treated with UDCA had decreased CC-depositions in atherosclerotic plaques compared to controls. Together, our data demonstrate that UDCA impaired CC and NLRP3 dependent inflammation by increasing cholesterol solubility and diminished atherosclerosis in mice. PMID:27416761

  3. Anti‐Inflammatory Immune Skewing Is Atheroprotective: Apoe−/−FcγRIIb−/− Mice Develop Fibrous Carotid Plaques

    OpenAIRE

    Harmon, Erin Y.; Van Fronhofer; Keller, Rebecca S.; Feustel, Paul J.; Zhu, Xinmei; Xu, Hao; Avram, Dorina; David M Jones; Nagarajan, Shanmugam; Lennartz, Michelle R.

    2014-01-01

    Background Stroke, caused by carotid plaque rupture, is a major cause of death in the United States. Whereas vulnerable human plaques have higher Fc receptor (FcγR) expression than their stable counterparts, how FcγR expression impacts plaque histology is unknown. We investigated the role of FcγRIIb in carotid plaque development and stability in apolipoprotein (Apo)e−/− and Apoe−/−FcγRIIb−/− double knockout (DKO) animals. Methods and Results Plaques were induced by implantation of a shear str...

  4. Biochemical Markers for Determining Vulnerable Atherosclerotic Plaque in Stenotic Patient: Biochemical Markers Study of Myeloperoxidase (MPO, Matrix Metallo-Proteinase-9 (MMP-9, Secretory Phospholipase A2 (SPLA2 and CD40 Ligand

    Directory of Open Access Journals (Sweden)

    Tommy Heryantho

    2009-08-01

    Full Text Available BACKGROUND: Thrombus is a main cause of cardiac death. Therefore identifying which coronary artery plaque is vulnerable to rupture is a critical step for cardiac intervention to prevent future cardiac events. Systemic biochemical markers are used for predicting rupture of coronary plaque or identifying stenotic coronary artery plaque(s vulnerable to rupture. METHODS: Blood samples of 2x24 locations (2x10 controls, 2x12 stable plaques and 2x2 unstable plaques of 13 patients to undergo stent placement were taken from an artery which showed no stenosis (control, 70% or more stenosis of stable plaques and unstable plaques, respectively. The blood samples were taken by using microcatheter distally and proximally. Concentrations of MPO, MMP-9, SPLA2 and CD40L of each sample were assayed. RESULTS: Concentration of MMP-9 in unstable coronary artery plaque (94.7+14.4 ng/ml significantly increased compared with that of stable coronary artery plaque (71.0+67.8 ng/ml, p=0.024. SPLA2 concentration significantly decreased in unstable coronary artery plaque (45.9+14.0 pg/ml compared with that of stable coronary artery plaque (80.9+39.3 pg/ml, p=0.015. Nine of ten studied subjects showed an average of 14.5% (range: 0.0-28.8% decrease of the SPLA2 concentration in stable plaques compared with that of the non-stenotic coronary artery. CONCLUSIONS: MMP-9 increased in unstable coronary artery plaque compared with that of stable coronary plaque. Unstable coronary artery plaques absorbed SPLA2 from the vasculars more than the stable plaques and control plaques. MMP-9 and SPLA2 may be used as markers of stability of a plaque in coronary artery in relation to its rupture potential. KEYWORDS: stable and unstable plaque, myeloperoxidase, matrix metalloproteinase-9, secretory phospholipase A2, CD40 ligand.

  5. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial

    Science.gov (United States)

    Fayad, Zahi A; Mani, Venkatesh; Woodward, Mark; Kallend, David; Abt, Markus; Burgess, Tracy; Fuster, Valentin; Ballantyne, Christie M; Stein, Evan A; Tardif, Jean-Claude; Rudd, James H F; Farkouh, Michael E; Tawakol, Ahmed

    2014-01-01

    Summary Background Dalcetrapib modulates cholesteryl ester transfer protein (CETP) activity to raise high-density lipoprotein cholesterol (HDL-C). After the failure of torcetrapib it was unknown if HDL produced by interaction with CETP had pro-atherogenic or pro-inflammatory properties. dal-PLAQUE is the first multicentre study using novel non-invasive multimodality imaging to assess structural and inflammatory indices of atherosclerosis as primary endpoints. Methods In this phase 2b, double-blind, multicentre trial, patients (aged 18–75 years) with, or with high risk of, coronary heart disease were randomly assigned (1:1) to dalcetrapib 600 mg/day or placebo for 24 months. Randomisation was done with a computer-generated randomisation code and was stratified by centre. Patients and investigators were masked to treatment. Coprimary endpoints were MRI-assessed indices (total vessel area, wall area, wall thickness, and normalised wall index [average carotid]) after 24 months and 18F-fluorodeoxyglucose (18F-FDG) PET/CT assessment of arterial inflammation within an index vessel (right carotid, left carotid, or ascending thoracic aorta) after 6 months, with no-harm boundaries established before unblinding of the trial. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00655473. Findings 189 patients were screened and 130 randomly assigned to placebo (66 patients) or dalcetrapib (64 patients). For the coprimary MRI and PET/CT endpoints, CIs were below the no-harm boundary or the adverse change was numerically lower in the dalcetrapib group than in the placebo group. MRI-derived change in total vessel area was reduced in patients given dalcetrapib compared with those given placebo after 24 months; absolute change from baseline relative to placebo was −4·01 mm2 (90% CI −7·23 to −0·80; nominal p=0·04). The PET/CT measure of index vessel most-diseased-segment target-to-background ratio (TBR) was not different between groups

  6. Atorvastatin Improves Plaque Stability in ApoE-Knockout Mice by Regulating Chemokines and Chemokine Receptors

    OpenAIRE

    Nie, Peng; Li, Dandan; Hu, Liuhua; Jin, Shuxuan; Yu, Ying; CAI, ZHAOHUA; SHAO, QIN; Shen, Jieyan; Yi, Jing; Xiao, Hua; Shen, Linghong; He, Ben

    2014-01-01

    It is well documented that statins protect atherosclerotic patients from inflammatory changes and plaque instability in coronary arteries. However, the underlying mechanisms are not fully understood. Using a previously established mouse model for vulnerable atherosclerotic plaque, we investigated the effect of atorvastatin (10 mg/kg/day) on plaque morphology. Atorvastatin did not lower plasma total cholesterol levels or affect plaque progression at this dosage; however, vulnerable plaque numb...

  7. Effect of Transmural Transport Properties on Atheroma Plaque Formation and Development.

    Science.gov (United States)

    Cilla, M; Martínez, M A; Peña, E

    2015-07-01

    We propose a mathematical model of atheroma plaque initiation and early development in coronary arteries using anisotropic transmural diffusion properties. Our current approach is on the process on plaque initiation and intimal thickening rather than in severe plaque progression and rupture phenomena. The effect of transport properties, in particular the anisotropy of diffusion properties of the artery, on plaque formation and development is investigated using the proposed mathematical model. There is not a strong influence of the anisotropic transmural properties on LDL, SMCs and collagen distribution and concentrations along the artery. On the contrary, foam cells distribution strongly depends on the value of the radial diffusion coefficient of the substances [Formula: see text] and the ratio [Formula: see text]. Decreasing [Formula: see text] or diffusion coefficients ratio means a higher concentration of the foam cells close to the intima. Due to the fact that foam cells concentration is associated to the necrotic core formation, the final distribution of foam cells is critical to evolve into a vulnerable or fibrotic plaque. PMID:25814436

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

    Institute of Scientific and Technical Information of China (English)

    Guo-ShengYang; Zhao-DianChen; Hong-JuWang

    2004-01-01

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

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

    OpenAIRE

    Apostolakis, Stavros; Chalikias, Georgios K; Tziakas, Dimitrios N; Konstantinides, Stavros

    2011-01-01

    Atherosclerosis is an inflammatory disease. The last three decades efforts have been made to elucidate the biochemical pathways that are implicated in the process of atherogenesis and plaque development. Chemokines are crucial mediators in every step of this process. Additionally, cellular components of the peripheral blood have been proved important mediators in the formation and progression of atherosclerotic lesions. However, until recently data were mostly focusing on leukocytes and plate...

  10. Peptidoglycan in atherosclerotic plaque formation and vulnerability

    OpenAIRE

    Oude Nijhuis, M.M.

    2006-01-01

    The studies described in this thesis suggest that peptidoglycan (PG) is involved in initiation and progression of atherosclerosis. PG is an antigen that can be found in large amounts in the Gram-positive bacterial wall and only in small amounts in the Gram-negative bacterial wall. PG is able to stimulate the Toll-like receptor 2 (TLR2), a receptor that plays an important role in the innate immune system. In the normal situation PG is present in the intestinal mucosal flora, but under certain ...

  11. Quantitative evaluation of high intensity signal on MIP images of carotid atherosclerotic plaques from routine TOF-MRA reveals elevated volumes of intraplaque hemorrhage and lipid rich necrotic core

    Directory of Open Access Journals (Sweden)

    Yamada Kiyofumi

    2012-11-01

    Full Text Available Abstract Background Carotid intraplaque hemorrhage (IPH and lipid rich necrotic core (LRNC have been associated with accelerated plaque growth, luminal narrowing, future surface disruption and development of symptomatic events. The aim of this study was to evaluate the quantitative relationships between high intensity signals (HIS in the plaque on TOF-MRA and IPH or LRNC volumes as measured by multicontrast weighted CMR. Methods Seventy six patients with a suspected carotid artery stenosis or carotid plaque by ultrasonography underwent multicontrast carotid CMR. HIS presence and volume were measured from TOF-MRA MIP images while IPH and LRNC volumes were separately measured from multicontrast CMR. Results For detecting IPH, HIS on MIP images overall had high specificity (100.0%, 95% CI: 93.0 – 100.0% but relatively low sensitivity (32%, 95% CI: 20.8 – 47.9%. However, the sensitivity had a significant increasing relationship with underlying IPH volume (p = 0.033 and degree of stenosis (p = 0.022. Mean IPH volume was 2.7 times larger in those with presence of HIS than in those without (142.8 ± 97.7 mm3 vs. 53.4 ± 56.3 mm3, p = 0.014. Similarly, mean LRNC volume was 3.4 times larger in those with HIS present (379.8 ± 203.4 mm3 vs. 111.3 ± 122.7 mm3, p = 0.001. There was a strong correlation between the volume of the HIS region and the IPH volume measured from multicontrast CMR (r = 0.96, p  Conclusion MIP images are easily reformatted from three minute, routine, clinical TOF sequences. High intensity signals in carotid plaque on TOF-MRA MIP images are associated with increased intraplaque hemorrhage and lipid-rich necrotic core volumes. The technique is most sensitive in patients with moderate to severe stenosis.

  12. Gender differences of atherosclerotic plaque characteristics in elderly patients with stable angina pectoris%血管内超声评价老年冠心病患者冠状动脉钙化病变的性别差异

    Institute of Scientific and Technical Information of China (English)

    王小飞; 陈欣; 王佩显

    2011-01-01

    Objective To evaluate the gender differences of atherosclerotic plaque characteristics in elderly patients with stabel angina pectoris using intravascular ultrasound(IVUS). Methods Sixty-one elderly patients with stable angina pectoris,age ≥65 years,male 33,female 28. One 50% -70% stenosis plaque was selected as target plaque in each patient. Coronary artery angiography and target plaque IVUS were performed to compare the vascular volume, lumen volume, plaque volume and calcification burden with arc area(AA). Results The vascular volume,lumen volume in female elderly patients were less than in male elderly patients(P<0. 05) ,there were no differences in plaque volume between male and female. AA in female patients was more than in male pa-tients(P<0. 05). Conclusion Female elderly patients with stable angina pectoris has smaller coronary artery and lumen at plaque segment as plaque burden was not different. Calcification burden in the plaque is more in female than in male patients.%目的 应用血管内超声评价不同性别老年冠心病患者冠状动脉粥样硬化斑块钙化情况.方法 选择年龄≥65岁稳定性心绞痛患者61例.所有患者均行冠状动脉造影,选取一处狭窄50%~70%的斑块进行血管内超声检查,测量血管、管腔、斑块体积及斑块钙化的弧面积.结果 女性患者血管体积和管腔体积较男性明显缩小,斑块钙化弧面积明显增加(P<0.05).结论 在斑块体积相同条件下,女性患者冠状动脉粥样硬化斑块部位血管体积和管腔体积小于男性,女性患者斑块钙化负荷明显高于男性.

  13. Effect of Aerobic Exercise and Dietary Fat on the Formation of Atherosclerotic Plaque in ApoE-Deficient Mice%有氧运动和膳食脂肪对ApoE基因缺陷小鼠动脉粥样硬化斑块形成的影响

    Institute of Scientific and Technical Information of China (English)

    陈近利; 陈吉棣

    2001-01-01

    为了探讨有氧运动和膳食因素在动脉粥样硬化斑块形成过程中的作用,研究了在跑台上进行的有氧运动和低脂膳食对ApoE基因缺陷小鼠动脉粥样硬化斑块形成过程的影响。结果表明:10周中等强度的有氧运动组和低脂膳食组ApoE基因缺陷小鼠主动脉窦处形成的动脉粥样硬化斑块面积均较对照组减少(P<0.05);有氧运动结合低脂膳食组ApoE基因缺陷小鼠的斑块面积分别低于单独的运动组和低脂膳食组(P<0.05)。研究提示有氧运动和低脂膳食均有利于并有效减轻动脉粥样硬化斑块的形成,有氧运动和低脂膳食两种因素结合的作用大于单独的有氧运动和低脂膳食的作用,二者在预防动脉粥样硬化斑块的形成上可能存在协同加强作用。%To approach the effects of aerobic exercise anddietary fat on the formation of atherosclerotic plaque, we have adopted the ApoE-gene knockout mice as the model to study the effects on an animal treadmill. The results show that the plaque area at the aortic sinuses of the exercised and low fat diet fed mice group were significantly reduced as comparing with the control group respectively. Mice of aerobic exercise and low fat diet combined treated group have the least lesion area of plaque as compared with the other groups. These results have indicated that either aerobic exercise or low fat diet is beneficial and effective to alleviate the formation of atherosclerotic lesions. However, aerobic combined with exercise can provide the greatest benefit in the alleviation of the formation of atherosclerotic plaque as compared with the single factor of either exercise or low fat diet.

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

    Directory of Open Access Journals (Sweden)

    Amir H. Najafi

    2013-03-01

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

  15. Interleukin 10-coated nanoparticle systems compared for molecular imaging of atherosclerotic lesions

    Directory of Open Access Journals (Sweden)

    Almer G

    2014-09-01

    Full Text Available Gunter Almer,1,* Kelli L Summers,1,2,* Bernhard Scheicher,2 Josef Kellner,3 Ingeborg Stelzer,1 Gerd Leitinger,4,5 Anna Gries,3 Ruth Prassl,6 Andreas Zimmer,2 Harald Mangge1,7 1Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; 2Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Graz, Austria; 3Institute of Physiological Chemistry, Medical University of Graz, Graz, Austria; 4Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria; 5Center for Medical Research (ZMF, Medical University of Graz, Graz, Austria; 6Institute of Biophysics, Medical University of Graz, Graz, Austria; 7BioTechMed, Graz, Austria*These authors contributed equally to the study Abstract: Atherosclerosis (AS is one of the leading causes of mortality in high-income countries. Early diagnosis of vulnerable atherosclerotic lesions is one of the biggest challenges currently facing cardiovascular medicine. The present study focuses on developing targeted nanoparticles (NPs in order to improve the detection of vulnerable atherosclerotic-plaques. Various biomarkers involved in the pathogenesis of atherosclerotic-plaques have been identified and one of these promising candidates for diagnostic targeting is interleukin 10 (IL10. IL10 has been shown to be a key anti-inflammatory responding cytokine in the early stages of atherogenesis, and has already been used for therapeutic interventions in humans and mice. IL10, the targeting sequence, was coupled to two different types of NPs: protamine-oligonucleotide NPs (proticles and sterically stabilized liposomes in order to address the question of whether the recognition and detection of atherosclerotic-lesions is primarily determined by the targeting sequence itself, or whether it depends on the NP carrier system to which the biomarker is coupled. Each

  16. Erythrocyte membrane, plasma and atherosclerotic plaque lipid pattern in coronary heart disease Perfil lipídico de membrana de eritrocito, plasma y placa ateromatosa en la enfermedad coronaria

    Directory of Open Access Journals (Sweden)

    Natalia R. Lausada

    2007-10-01

    Full Text Available The objective was to analyze the lipid composition of the atherosclerotic plaque (AP, plasma and erythrocyte membrane (EM in patients with advanced coronary heart disease (CHD. AP were obtained through endarterectomy in 18 patients. Ten normolipemic healthy subjects were selected to obtain the normal lipid pattern profile. Total lipids of AP and EM were determined by HPTLC, and the fatty acid profile from AP, EM and plasma using TLC-FID. The relative amount of the lipid species analyzed in AP was in line with the data in the literature [phospholipids: 23.5 mol% ± 3.5; total cholesterol 68.9 mol% ± 7.9; triglyceride 7.6 mol% ± 3.4]. Plasma and EM from CHD patients compared to controls, showed a decrease in polyunsaturated fatty acids and an increase in saturated fatty acids leading to a decrease in the unsaturation index (plasma: 1.67 ± 0.06 vs. 1.28 ± 0.03, PEl objetivo fue analizar la composición lipídica de las membranas de eritrocitos (ME, plasma y placas ateromatosas (PA en pacientes con enfermedad coronaria avanzada (ECV. Las PA fueron obtenidas de endarterectomías coronarias de 18 pacientes. Fueron seleccionados 10 sujetos sanos, normolipémicos, como grupo control. Los lípidos totales de PA y ME se determinaron utilizando HPTLC, y el perfil de ácidos grasos de las PA, ME y plasma mediante TLC-FID. La cantidad relativa de las especies lipídicas obtenidas de las PA coinciden con la literatura [fosfolípidos 23.5 mol% ± 3.5; colesterol total 68.9 mol% ± 7.9; triglicéridos 7.6 mol% ± 3.4]. En el plasma y en las ME de los pacientes con ECV se observó, comparando con los pacientes controles, una disminución de los ácidos grasos poli-no saturados acompañado de un aumento de los ácidos grasos saturados que provocó el descenso del índice de instauración (plasma: 1.67 ± 0.06 vs. 1.28 ± 0.03, P<0.05; ME: 2.28 ± 0.04 vs. 1.25 ± 0.010, P<0.05 y el incremento del cociente AG saturados/insaturados (plasma: 0.35 ± 0.02 vs. 0

  17. The bile acid sensor FXR protects against dyslipidemia and aortic plaques development induced by the HIV protease inhibitor ritonavir in mice.

    Directory of Open Access Journals (Sweden)

    Andrea Mencarelli

    Full Text Available BACKGROUND: Although human immunodeficiency virus (HIV-related morbidity and mortality rates in patients treated with a combination of high active antiretroviral therapy (HAART have declined, significant metabolic/vascular adverse effects associated with the long term use of HIV protease inhibitors (PIs have emerged as a significant side effect. Here we illustrate that targeting the bile acid sensor farnesoid X receptor (FXR protects against dyslipidemia and vascular injury induced HIV-PIs in rodents. METHODOLOGY/PRINCIPAL FINDINGS: Administration of the HIV PI ritonavir to wild type mice increased plasma triacylglycerols and cholesterol levels and this effect was exacerbated by dosing ritonavir to mice harbouring a disrupted FXR. Dyslipidemia induced by ritonavir associated with a shift in the liver expression of signature genes, Sterol Regulatory Element-Binding Protein (SREBP-1 and fatty acid synthase. Treating wild type mice with the FXR agonist (chenodeoxycholic acid, CDCA protected against development of dyslipidemia induced by ritonavir. Administration of ritonavir to ApoE(-/- mice, a strain that develop spontaneously atherosclerosis, increased the extent of aortic plaques without worsening the dyslipidemia. Treating these mice with CDCA reduced the extent of aortic plaques by 70% without changing plasma lipoproteins or the liver expression of signature genes. A beneficial effect on aortic plaques was also obtained by treating ApoE(-/- mice with gemfibrozil, a PPARα agonist. FXR activation counter-regulated induction of expression/activity of CD36 caused by HIV-PIs in circulating monocytes and aortic plaques. In macrophages cell lines, CDCA attenuated CD36 induction and uptake of acetylated LDL caused by ritonavir. Natural and synthetic FXR ligands reduced the nuclear translocation of SREBP1c caused by ritonavir. CONCLUSIONS/SIGNIFICANCE: Activation of the bile acid sensor FXR protects against dyslipidemia and atherosclerotic caused by

  18. Statistical segmentation of carotid plaque neovascularization

    Science.gov (United States)

    Akkus, Zeynettin; Bosch, Johan G.; Sánchez-Ferrero, Gonzalo V.; Carvalho, Diego D. B.; Renaud, Guillaume; van den Oord, Stijn C. H.; ten Kate, Gerrit L.; Schinkel, Arend F. L.; de Jong, Nico; van der Steen, Antonius F. W.

    2013-03-01

    In several studies, intraplaque neovascularization (IPN) has been linked with plaque vulnerability. The recent development of contrast enhanced ultrasound enables IPN detection, but an accurate quantification of IPN is a big challenge due to noise, motion, subtle contrast response, blooming of contrast and artifacts. We present an algorithm that automatically estimates the location and amount of contrast within the plaque over time. Plaque pixels are initially labeled through an iterative expectation-maximization (EM) algorithm. The used algorithm avoids several drawbacks of standard EM. It is capable of selecting the best number of components in an unsupervised way, based on a minimum message length criterion. Next, neighborhood information using a 5×5 kernel and spatiotemporal behavior are combined with the known characteristics of contrast spots in order to group components, identify artifacts and finalize the classification. Image sequences are divided into 3-seconds subgroups. A pixel is relabeled as an artifact if it is labeled as contrast for more than 1.5 seconds in at least two subgroups. For 10 plaques, automated segmentation results were validated with manual segmentation of contrast in 10 frames per clip. Average Dice index and area ratio were 0.73+/-0.1 (mean+/-SD) and 98.5+/-29.6 (%) respectively. Next, 45 atherosclerotic plaques were analyzed. Time integrated IPN surface area was calculated. Average area of IPN was 3.73+/-3.51 mm2. Average area of 45 plaques was 11.6+/-8.6 mm2. This method based on EM contrast segmentation provides a new way of IPN quantification.

  19. ARTreat Project: Three-Dimensional Numerical Simulation of Plaque Formation and Development in the Arteries

    OpenAIRE

    Filipovic, N.; Rosic, M; Tanaskovic, I.; Milosevic, Z; Nikolic, D.; Zdravkovic, N.; A. Peulic; Kojic, M.R.; Fotiadis, D.; Parodi, O.

    2011-01-01

    Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in arteries. It is characterized by dysfunction of endothelium and vasculitis, and accumulation of lipid, cholesterol, and cell elements inside blood vessel wall. In this study, a continuum-based approach for plaque formation and development in 3-D is presented. The blood flow is simulated by the 3-D Navier-Stokes equations, together with the continuity equation while low-density lipoprot...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  1. In vivo and in vitro evidence that {sup 99m}Tc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery

    Energy Technology Data Exchange (ETDEWEB)

    Glaudemans, Andor W.J.M.; Vries, Erik F.J. de; Koole, Michel; Luurtsema, Gert; Slart, Riemer H.J.A. [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Bonanno, Elena [Univ. of Rome Tor Vergata (Italy). Dept. of Anatomic Pathology; Galli, Filippo [Sapienza Univ, Rome (Italy). Nuclear Medicine Unit; Zeebregts, Clark J. [University Medical Center Groningen (Netherlands). Surgery (Div. Vascular Surgery); Boersma, Hendrikus H. [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; University Medical Center Groningen (Netherlands). Clinical and Hospital Pharmacy; Taurino, Maurizio [Sapienza Univ., Rome (Italy). Vascular Surgery Unit; Signore, Alberto [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Sapienza Univ, Rome (Italy). Nuclear Medicine Unit

    2014-09-15

    Recent advances in basic science have established that inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Inflammatory cells are thought to be responsible for the transformation of a stable plaque into a vulnerable one. Lymphocytes constitute at least 20 % of infiltrating cells in these vulnerable plaques. Therefore, the interleukin-2 (IL-2) receptor, being overexpressed on activated T lymphocytes, may represent an attractive biomarker for plaque vulnerability. The aim of this study was to evaluate the specificity of radiolabelled IL-2 [{sup 99m}Tc-hydrazinonicotinamide (HYNIC)-IL-2] for imaging the lymphocytic infiltration in carotid plaques in vivo by planar and single photon emission computed tomography (SPECT)/CT imaging and ex vivo by microSPECT and autoradiography. For the in vivo study, ten symptomatic patients with advanced plaques at ultrasound who were scheduled for carotid endarterectomy underwent {sup 99m}Tc-HYNIC-IL-2 scintigraphy. The images were analysed visually on planar and SPECT images and semi-quantitatively on SPECT images by calculating target to background (T/B) ratios. After endarterectomy, immunomorphological evaluation and immunophenotyping were performed on plaque slices. For the ex vivo studies, four additional patients were included and, after in vitro incubation of removed plaques with {sup 99m}Tc-HYNIC-IL-2, autoradiography was performed and microSPECT images were acquired. Visual analysis defined clear {sup 99m}Tc-HYNIC-IL-2 uptake in seven of the ten symptomatic plaques. SPECT/CT allowed visualization in eight of ten. A significant correlation was found between the number of CD25+ lymphocytes and the total number of CD25+ cells in the plaque and the T/B ratio with adjacent carotid artery as background (Pearson's r = 0.89, p = 0.003 and r = 0.87, p = 0.005, respectively). MicroSPECT imaging showed clear {sup 99m}Tc-HYNIC-IL-2 uptake within the plaque wall and not in the lipidic core. With autoradiography

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

    Directory of Open Access Journals (Sweden)

    Tanasković Irena

    2013-01-01

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

  3. Curcumin as a novel plaque stabilizing agent in prevention of acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Jamal Shamsara

    2009-05-01

    Full Text Available "nCurcumin (diferuloylmethane is an active component of the spice turmeric and has been linked with anti-inflammatory and chemopreventive activities. The present hypothesis explained the involvement of anti-inflammatory effects of crcumin in prevention of acute coronary syndromes (ACS (i.e. unstable angina and myocardial infarction. ACS is the leading cause of death in both developed and developing countries. Coronary events often result from thrombi that form because of physical disruption of the atherosclerotic plaque. However, despite lipid lowing therapy with statins, significant numbers of cardiovascular events continue to occur indicating the need for additional agents for atherosclerosis management. We proposed that curcumin therapy can stabilize vulnerable 'rupture-prone' plaques by normalizing plaque properties. Thus, co-administration of curcumin along with other present options may prove to be a useful and potent natural plaque stabilizing approach in the prevention of ACS.

  4. Evaluation of texture parameters for the quantitative description of multimodal nonlinear optical images from atherosclerotic rabbit arteries

    International Nuclear Information System (INIS)

    The composition and structure of atherosclerotic lesions can be directly related to the risk they pose to the patient. Multimodal nonlinear optical (NLO) microscopy provides a powerful means to visualize the major extracellular components of the plaque that critically determine its structure. Textural features extracted from NLO images were investigated for their utility in providing quantitative descriptors of structural and compositional changes associated with plaque development. Ten texture parameters derived from the image histogram and gray level co-occurrence matrix were examined that highlight specific structural and compositional motifs that distinguish early and late stage plaques. Tonal-texture parameters could be linked to key histological features that characterize vulnerable plaque: the thickness and density of the fibrous cap, size of the atheroma, and the level of inflammation indicated through lipid deposition. Tonal and texture parameters from NLO images provide objective metrics that correspond to structural and biochemical changes that occur within the vessel wall in early and late stage atherosclerosis.

  5. Evaluation of texture parameters for the quantitative description of multimodal nonlinear optical images from atherosclerotic rabbit arteries

    Energy Technology Data Exchange (ETDEWEB)

    Mostaco-Guidolin, Leila B; Ko, Alex C-T; Popescu, Dan P; Smith, Michael S D; Kohlenberg, Elicia K; Sowa, Michael G [Institute for Biodiagnostics, National Research Council Canada, Winnipeg, R3B 1Y6 (Canada); Shiomi, Masashi [Institute of Experimental Animals, School of Medicine, Kobe University, Kobe 650-0017 (Japan); Major, Arkady [Department Electrical and Computer Engineering, University of Manitoba, E3-559 Engineering Building, Winnipeg, R3T 5V6 (Canada)

    2011-08-21

    The composition and structure of atherosclerotic lesions can be directly related to the risk they pose to the patient. Multimodal nonlinear optical (NLO) microscopy provides a powerful means to visualize the major extracellular components of the plaque that critically determine its structure. Textural features extracted from NLO images were investigated for their utility in providing quantitative descriptors of structural and compositional changes associated with plaque development. Ten texture parameters derived from the image histogram and gray level co-occurrence matrix were examined that highlight specific structural and compositional motifs that distinguish early and late stage plaques. Tonal-texture parameters could be linked to key histological features that characterize vulnerable plaque: the thickness and density of the fibrous cap, size of the atheroma, and the level of inflammation indicated through lipid deposition. Tonal and texture parameters from NLO images provide objective metrics that correspond to structural and biochemical changes that occur within the vessel wall in early and late stage atherosclerosis.

  6. Development of rampant dental caries, and composition of plaque fluid and saliva in irradiated primates

    International Nuclear Information System (INIS)

    Co-60 gamma irradiation of the salivary glands of Macaca mulata monkeys fed a cariogenic diet led to the rapid onset of dental caries resembling that in irradiated human patients. Plaque fluid and saliva were sampled from irradiated monkeys, nonirradiated controls and a group of animals fed a noncariogenic diet in order to look for changes which might occur in inorganic composition related to the caries development and to dietary differences. Salivary calcium and phosphate levels were not markedly changed after irradiation: iodide levels were raised, while thiocyanate levels fell. In plaque fluid, calcium concentrations were not affected by irradiation, but were higher in animals fed a noncariogenic diet. Phosphate levels were higher with a cariogenic diet and further increased in irradiated animals. Magnesium levels were occasionally higher than those of calcium. Other differences in plaque fluid composition may be related to secondary effects of the concomitant gingival disease. The results do not point clearly a specific change in the quality of the saliva produced by the residual gland tissue after irradiation which precipitates the rampant caries. It is more likely that the grat reduction in the quantity of saliva with its protective constituents is responsible. (author)

  7. A comparison of herpes simplex virus plaque development after viral treatment with anti-DNA or antilipid agents.

    OpenAIRE

    Coohill, T P; Babich, M; Taylor, W.D.; Snipes, W

    1980-01-01

    The plaque development of Herpes simplex virus type 1 (HSV) is slower for viruses treated with two anti-DNA agents: ultraviolet radiation (UV) or n-acetoxy-2-acetyl-aminofluorene. For HSV treated with three antimembrane agents--butylated hydroxytoluene, acridine plus near UV radiation, or ether--the plaque development time is the same as for untreated viruses. These differences hold even for viruses that survived treatment that lowered viability below the 1% level. Gamma ray inactivation of H...

  8. Plaque development, vessel curvature, and wall shear stress in coronary arteries assessed by X-ray angiography and intravascular ultrasound

    OpenAIRE

    Wahle, Andreas; Lopez, John J.; Olszewski, Mark E.; Vigmostad, Sarah C.; Chandran, Krishnan B.; Rossen, James D.; Sonka, Milan

    2006-01-01

    The relationships among vascular geometry, hemodynamics, and plaque development in the coronary arteries are complex and not yet well understood. This paper reports a methodology for the quantitative analysis of in vivo coronary morphology and hemodynamics, with particular emphasis placed on the critical issues of image segmentation and the automated classification of disease severity. We were motivated by the observation that plaque more often developed at the inner curvature of a vessel, pr...

  9. Plaque characterization in ex vivo MRI evaluated by dense 3D correspondence with histology

    DEFF Research Database (Denmark)

    Engelen, A. van; de Bruijne, Marleen; Klein, S.;

    2011-01-01

    . Histological slices of human atherosclerotic plaques were manually segmented into necrotic core, fibrous tissue and calcification. Classification of these three components was voxelwise evaluated. As features the intensity, gradient magnitude and Laplacian in four MRI sequences after different degrees of......Automatic quantification of carotid artery plaque composition is important in the development of methods that distinguish vulnerable from stable plaques. MRI has shown to be capable of imaging different components noninvasively. We present a new plaque classification method which uses 3D...... registration of histology data with ex vivo MRI data, using non-rigid registration, both for training and evaluation. This is more objective than previously presented methods, as it eliminates selection bias that is introduced when 2D MRI slices are manually matched to histological slices before evaluation...

  10. Development of a selective medium for detection and enumeration of Actinomyces viscosus and Actinomyces naeslundii in dental plaque.

    OpenAIRE

    Zylber, L J; Jordan, H. V.

    1982-01-01

    A selective medium (CFAT) was developed for the detection and enumeration of Actinomyces viscosus and Actinomyces naeslundii in dental plaque. Neutral acriflavin and potassium tellurite were used in combination with the known selective agents cadmium and fluoride to eliminate most of the competing plaque flora. Composition of CFAT per liter was as follows: Trypticase soy broth (BBL Microbiology Systems), 30 g; glucose, 5 g; agar, 15 g' cadmium sulfate, 13 mg; sodium fluoride, 85 mg; neutral a...

  11. Atherosclerotic Calcification Detection: A Comparative Study of Carotid Ultrasound and Cone Beam CT

    Directory of Open Access Journals (Sweden)

    Fisnik Jashari

    2015-08-01

    Full Text Available Background and Aim: Arterial calcification is often detected on ultrasound examination but its diagnostic accuracy is not well validated. The aim of this study was to determine the accuracy of carotid ultrasound B mode findings in detecting atherosclerotic calcification quantified by cone beam computed tomography (CBCT. Methods: We analyzed 94 carotid arteries, from 88 patients (mean age 70 ± 7 years, 33% females, who underwent pre-endarterectomy ultrasound examination. Plaques with high echogenic nodules and posterior shadowing were considered calcified. After surgery, the excised plaques were examined using CBCT, from which the calcification volume (mm3 was calculated. In cases with multiple calcifications the largest calcification nodule volume was used to represent the plaque. Carotid artery calcification by the two imaging techniques was compared using conventional correlations. Results: Carotid ultrasound was highly accurate in detecting the presence of calcification; with a sensitivity of 88.2%. Based on the quartile ranges of calcification volumes measured by CBCT we have divided plaque calcification into four groups: <8; 8–35; 36–70 and >70 mm3. Calcification volumes ≥8 were accurately detectable by ultrasound with a sensitivity of 96%. Of the 21 plaques with <8 mm3 calcification volume; only 13 were detected by ultrasound; resulting in a sensitivity of 62%. There was no difference in the volume of calcification between symptomatic and asymptomatic patients. Conclusion: Carotid ultrasound is highly accurate in detecting the presence of calcified atherosclerotic lesions of volume ≥8 mm3; but less accurate in detecting smaller volume calcified plaques. Further development of ultrasound techniques should allow better detection of early arterial calcification.

  12. Atherosclerotic Calcification Detection: A Comparative Study of Carotid Ultrasound and Cone Beam CT

    Science.gov (United States)

    Jashari, Fisnik; Ibrahimi, Pranvera; Johansson, Elias; Ahlqvist, Jan; Arnerlöv, Conny; Garoff, Maria; Levring Jäghagen, Eva; Wester, Per; Henein, Michael Y.

    2015-01-01

    Background and Aim: Arterial calcification is often detected on ultrasound examination but its diagnostic accuracy is not well validated. The aim of this study was to determine the accuracy of carotid ultrasound B mode findings in detecting atherosclerotic calcification quantified by cone beam computed tomography (CBCT). Methods: We analyzed 94 carotid arteries, from 88 patients (mean age 70 ± 7 years, 33% females), who underwent pre-endarterectomy ultrasound examination. Plaques with high echogenic nodules and posterior shadowing were considered calcified. After surgery, the excised plaques were examined using CBCT, from which the calcification volume (mm3) was calculated. In cases with multiple calcifications the largest calcification nodule volume was used to represent the plaque. Carotid artery calcification by the two imaging techniques was compared using conventional correlations. Results: Carotid ultrasound was highly accurate in detecting the presence of calcification; with a sensitivity of 88.2%. Based on the quartile ranges of calcification volumes measured by CBCT we have divided plaque calcification into four groups: 70 mm3. Calcification volumes ≥8 were accurately detectable by ultrasound with a sensitivity of 96%. Of the 21 plaques with <8 mm3 calcification volume; only 13 were detected by ultrasound; resulting in a sensitivity of 62%. There was no difference in the volume of calcification between symptomatic and asymptomatic patients. Conclusion: Carotid ultrasound is highly accurate in detecting the presence of calcified atherosclerotic lesions of volume ≥8 mm3; but less accurate in detecting smaller volume calcified plaques. Further development of ultrasound techniques should allow better detection of early arterial calcification. PMID:26307978

  13. 血浆同型半胱氨酸水平与缺血性脑血管病患者颈动脉粥样硬化斑块的相关性研究%Relationship of plasma homocysteine and carotid atherosclerotic plaque in patients with ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    李世敬; 金亚娟; 赵玉燕

    2016-01-01

    目的:研究血浆同型半胱氨酸水平和缺血性脑血管病患者颈动脉粥样硬化斑块的相关性。方法:选择2014年10月~2015年11月在我院进行诊治的缺血性脑血管病患者500例,进行颈动脉彩色多普勒超声检查后,根据超声结果分为无斑块组(106例)、不稳定斑块组(261例)与稳定斑块组(133例),检测血浆同型半胱氨酸水平,并分析其与颈动脉粥样硬化斑块的相关性。结果:500例患者中发现无斑块106例(21.2%),颈动脉斑块394例(78.8%);稳定斑块组和不稳定斑块组的血浆同型半胱氨酸水平较无斑块组明显升高;不稳定斑块组与稳定斑块组相比,同型半胱氨酸水平均明显升高;易损斑块组血浆同型半胱氨酸浓度和高同型半胱氨酸血症发生率均明显高于非易损斑块组;Logistic 回归分析结果显示同型半胱氨酸的水平与颈动脉硬化斑块呈正性相关关系,OR 为1.23,95% CI 为1.021.22,差异有统计学意义。结论:颈动脉斑块的形成及其稳定性与同型半胱氨酸水平关系紧密,同型半胱氨酸水平升高是颈动脉斑块形成的独立危险因子。%Objective To investigate the relationship of plasma homocysteine and carotid atherosclerotic plaque in patients with ischemic cerebrovascular disease. Methods Selected 5000 cases of patients with ischemic cerebrovascular disease who were treated in our hospital from September 2014 to November 2015. According to the results of carotid color Doppler ultra-sound examination, divided into no plaque group (106 cases), unstable plaque group (261 cases) and stable plaque group (133 cases). Detected the levels of plasma homocysteine and analyzed their correlation with carotid atherosclerosis plaque. Results Of the 500 patients, 106 patients (21.2%) had no plaque, and 394 patients (78.8%) had carotid plaques no plaque was found in 106 cases(21.2%), 394 cases (78.8%) of carotid

  14. Semi-automated segmentation of carotid artery total plaque volume from three dimensional ultrasound carotid imaging

    Science.gov (United States)

    Buchanan, D.; Gyacskov, I.; Ukwatta, E.; Lindenmaier, T.; Fenster, A.; Parraga, G.

    2012-03-01

    Carotid artery total plaque volume (TPV) is a three-dimensional (3D) ultrasound (US) imaging measurement of carotid atherosclerosis, providing a direct non-invasive and regional estimation of atherosclerotic plaque volume - the direct determinant of carotid stenosis and ischemic stroke. While 3DUS measurements of TPV provide the potential to monitor plaque in individual patients and in populations enrolled in clinical trials, until now, such measurements have been performed manually which is laborious, time-consuming and prone to intra-observer and inter-observer variability. To address this critical translational limitation, here we describe the development and application of a semi-automated 3DUS plaque volume measurement. This semi-automated TPV measurement incorporates three user-selected boundaries in two views of the 3DUS volume to generate a geometric approximation of TPV for each plaque measured. We compared semi-automated repeated measurements to manual segmentation of 22 individual plaques ranging in volume from 2mm3 to 151mm3. Mean plaque volume was 43+/-40mm3 for semi-automated and 48+/-46mm3 for manual measurements and these were not significantly different (p=0.60). Mean coefficient of variation (CV) was 12.0+/-5.1% for the semi-automated measurements.

  15. Plaque rupture in humans and mice

    DEFF Research Database (Denmark)

    Schwartz, Stephen M; Galis, Zorina S; Rosenfeld, Michael E;

    2007-01-01

    Despite the many studies of murine atherosclerosis, we do not yet know the relevance of the natural history of this model to the final events precipitated by plaque disruption of human atherosclerotic lesions. The literature has become particularly confused because of the common use of terms such...

  16. High-normal blood pressure and carotid atherosclerotic plaque formation: The results from stroke population screening in Dongying, Shandong province%正常高值血压与颈动脉粥样硬化斑块形成:来自山东东营卒中筛查人群的结果

    Institute of Scientific and Technical Information of China (English)

    吴德云; 刘迎春; 高宗恩; 李楠; 杨志杰

    2014-01-01

    目的 探讨不同血压水平与颈动脉粥样斑块形成的相关性.方法 从2012年9月至2013年1月期间参加东营市卒中筛查的人群中,选取符合理想血压[收缩压(systolic blood pressure,SBP)< 120 mm Hg且舒张压(diastolic blood pressure,DBP)< 80 mm Hg,1 mm Hg =0.133 kPa]、正常血压[SBP 120~129 mm Hg和(或)DBP 80 ~84 mm Hg]和正常高值血压[SBP 130~139 mm Hg和(或)DBP 85~89 mm Hg]诊断标准的人群为研究对象,进行间卷调查、体格检查、血生化检查及颈部血管超声检查.比较正常血压组、正常高值血压组与理想血压组之间颈动脉斑块检出率,进行多变量logistic回归分析确定颈动脉斑块的独立危险因素.结果 正常血压组和正常高值血压组男性和糖尿病的构成比以及体质指数(body mass index,BMI)和空腹血糖(fasting blood glucose,FBG)水平均显著性高于理想血压组(P均<0.05).理想血压组、正常血压组和正常高值血压组颈动脉斑块检出率分别为12.41%、38.14%和49.45%.颈动脉斑块形成组男性构成比以及年龄、SBP、FBG和高半胱氨酸(homocysteine,Hcy)水平均显著性高于无颈动脉斑块形成组(P均<0.05).多变量logistic回归分析显示,年龄、SBP、FBG和Hcy为颈动脉粥样斑块形成的独立危险因素,女性为独立保护因素.在校正性别、年龄、FBG和Hcy等危险因素后,正常高值血压组斑块形成风险显著性高于理想血压组(优势比1.354,95%可信区间1.028~1.783;P=0.031),而正常血压组与理想血压组无显著性差异.结论 正常高值血压与颈动脉斑块形成风险增高显著相关,是颈动脉斑块形成的独立危险因素.%Objective To investigate the correlation between different blood pressure levels and carotid atherosclerotic plaque formation.Methods The population participated in stroke screening were selected from September 2012 to January 2013 in Dongying,Shandong province.The subjects met the

  17. Expression of NPP1 is regulated during atheromatous plaque calcification

    OpenAIRE

    Nitschke, Yvonne; Hartmann, Simone; Torsello, Giovanni; Horstmann, Rüdiger; Seifarth, Harald; Weissen-Plenz, Gabriele; Rutsch, Frank

    2009-01-01

    Abstract Mutations of the ENPP1 gene encoding ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) are associated with medial calcification in infancy. While the inhibitory role of matrix proteins such as osteopontin (OPN) with respect to atherosclerotic plaque calcification has been established, the role of NPP1 in plaque calcification is not known. We assessed the degree of plaque calcification (computed tomography), NPP1 and OPN localization (immunohistochemistry) and expression (RT-...

  18. Spiral computed tomographic imaging related to computerized ultrasonographic images of carotid plaque morphology and histology

    DEFF Research Database (Denmark)

    Grønholdt, Marie-Louise; Wagner, A; Wiebe, B M;

    2001-01-01

    Echolucency of carotid atherosclerotic plaques, as evaluated by computerized B-mode ultrasonographic images, has been associated with an increased incidence of brain infarcts on cerebral computed tomographic scans. We tested the hypotheses that characterization of carotid plaques on spiral computed...... tomographic images correlates with that on computerized B-mode ultrasonographic images and that spiral computed tomographic imaging predicts the histomorphometric plaque content....

  19. Relevance analysis of health behaviors and influencing factors for detection rate of carotid atherosclerotic plaque%影响颈动脉斑块检出率的相关因素分析

    Institute of Scientific and Technical Information of China (English)

    蒋树中; 刘茹; 韩冰

    2014-01-01

    Objective To explore the relevance of health behaviors and influencing factors for detection rate of carotid plaques to prevent the formation of carotid plaque.Methods A total of 2 628 healthy subjects aged over 40 years were selected randomly from Department of Cardiology at our hospital from 2009-2010.A questionnaire survey was conducted on age , education level, marriage, occupation, income, diet, living habits and lifestyle factors.Logistic regression analysis was made for the influencing factors of internal carotid artery plaque.Results Single factor analysis showed that gender , age, smoking rate, fasting blood glucose , blood pressure , carotid artery intima-media thickness ( intima-media thickness , IMT), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol ( LDL-C ) had significant effects on plaque formation.Multivariate Logistic regression analysis showed that gender , age, TG, LDL-C, HDL-C and number of health behaviors were the major influencing factors for the formation of carotid plaque.Compared with the 5 ideal cardiovascular health behaviors/factors and occurrence of carotid plaques were 0.65, 0.45, 0.39 and 0.29 respectively.Conclusions The formation of carotid plaque is affected by many factors.The number of ideal cardiovascular health behaviors is negatively correlated with plaque formation and it can prevent the occurrence of carotid plaque .%目的:探讨影响颈内动脉斑块检出率的相关健康行为和相关因素。方法选取2009-2010年间在江苏省徐州市心血管病研究所心内科进行健康体检的人员作为研究对象。采用分层随机抽样的方法从中抽取40岁以上2628例纳入研究。制定调查问卷,并对年龄、文化程度、婚姻、职业、经济收入、饮食习惯、生活习惯、生活行为因素进行调查。应用Logistic回归分析对影响颈内动脉斑块的因素进行统计分析。结果单因素

  20. Modeling plaque fissuring and dissection during balloon angioplasty intervention.

    Science.gov (United States)

    Gasser, T Christian; Holzapfel, Gerhard A

    2007-05-01

    Balloon angioplasty intervention is traumatic to arterial tissue. Fracture mechanisms such as plaque fissuring and/or dissection occur and constitute major contributions to the lumen enlargement. However, these types of mechanically-based traumatization of arterial tissue are also contributing factors to both acute procedural complications and chronic restenosis of the treatment site. We propose physical and finite element models, which are generally useable to trace fissuring and/or dissection in atherosclerotic plaques during balloon angioplasty interventions. The arterial wall is described as an anisotropic, heterogeneous, highly deformable, nearly incompressible body, whereas tissue failure is captured by a strong discontinuity kinematics and a novel cohesive zone model. The numerical implementation is based on the partition of unity finite element method and the interface element method. The later is used to link together meshes of the different tissue components. The balloon angioplasty-based failure mechanisms are numerically studied in 3D by means of an atherosclerotic-prone human external iliac artery, with a type V lesion. Image-based 3D geometry is generated and tissue-specific material properties are considered. Numerical results show that in a primary phase the plaque fissures at both shoulders of the fibrous cap and stops at the lamina elastica interna. In a secondary phase, local dissections between the intima and the media develop at the fibrous cap location with the smallest thickness. The predicted results indicate that plaque fissuring and dissection cause localized mechanical trauma, but prevent the main portion of the stenosis from high stress, and hence from continuous tissue damage. PMID:17385047

  1. Iron-oxide-enhanced MR imaging of inflammatory atherosclerotic lesions: overview of experimental and initial clinical results

    International Nuclear Information System (INIS)

    Numerous pathologic studies in the 1990's have shown atherosclerosis to be a chronic inflammatory disorder. This new insight and the advent of new plaque-stabilizing drugs, in particular antilipemic agents (statins), have led to an increased clinical interest in the development of new imaging modalities. These are aimed at visualizing the inflammatory atherosclerotic wall lesion as reflecting the active progression of the disease process and at identifying so-called vulnerable or high-risk lesions that are associated with a higher rate of vascular complications. A diagnostic modality currently undergoing investigation in terms of its potential for the diagnostic assessment of atherosclerosis is contrast-enhanced magnetic resonance imaging (MRI) using certain blood pool contrast media such as ultrasmall superparamagnetic iron oxide (USPIO) particles. Endothelial dysfunction and macrophage infiltration are two crucial pathomechanisms of atherosclerosis and these mechanisms also underlie the accumulation of iron oxide particles in experimental and human atherosclerotic lesions. Experimental results furthermore suggest that there is selective uptake of iron oxide by thrombi. The following experimental MR imaging techniques have a potential for providing complementary diagnostic information in assessing atherosclerotic lesions: 1. Unenhanced MRI for visualizing vulnerable plaques (wall thickness, fibrous cap, lipid core). 2. Visualization of the vessel lumen and quantitative assessment of stenosis using iron-oxide-enhanced MR angiography. 3. Delayed MRI studies for the functional characterization of inflammatory lesions (T2-effects produced by iron oxide uptake in macrophages of inflammatory lesions) with a potential for identifying mural thrombus as a sign of plaque rupture (T1-effects produced by binding of iron oxide to the thrombus). This article presents the experimental and initial clinical results obtained with iron-oxide-enhanced MRI of atherosclerotic lesions

  2. Surface expression of CXCR4 on circulating CD133+ progenitor cells is associated with plaque instability in subjects with carotid artery stenosis

    Directory of Open Access Journals (Sweden)

    Sadikovic Suwad

    2009-12-01

    Full Text Available Abstract Background Circulating progenitor cells (PCs are considered to contribute to the remodeling of atherosclerotic plaques. Their surface receptor CXCR4 plays an important role in the recruitment of PCs to their target. This study compares the mobilization of PCs and their functional characteristics in asymptomatic subjects with stable and with unstable carotid plaques. This could provide insight into plaque remodeling and help to develop biomarkers for plaque stability. Methods In 31 subjects with asymptomatic carotid artery stenosis we analyzed the number of CD133+ PCs, VEGFR2+CD34+ PCs and the surface expression of CXCR4 on CD133+ PCs by flow cytometry. Subjects underwent bilateral carotid MRI in a 1.5-T scanner in order to allow the categorization of plaques, following the modified criteria of the American Heart Association. Results The number of CD133+ PCs and VEGFR2+CD34+ PCs showed no significant difference between subjects with stable and unstable carotid plaques. The expression of CXCR4 on CD133+ PCs was higher in subjects with unstable plaques than in subjects with stable plaques (p = 0.009. Conclusions This study demonstrates an association between functional characteristics of circulating CD133+ PCs and plaque stability in subjects with asymptomatic carotid artery stenosis. The higher expression of CXCR4 on CD133+ PCs suggests a difference in the recruitment of PCs to the injured tissue in subjects with unstable plaques and subjects with stable plaques. As surface expression of CXCR4 on CD133+ PCs differs in subjects with unstable and with stable plaques, CXCR4 is a promising candidate for a serological biomarker for plaque stability.

  3. Development of a novel plaque reduction neutralisation test for hantavirus infection

    OpenAIRE

    Michelly de Pádua; William Marciel de Souza; Flávio Lauretti; Luiz Tadeu Moraes Figueiredo

    2015-01-01

    In the Americas, hantaviruses cause severe cardiopulmonary syndrome (HCPS) with a high fatality rate. Hantavirus infection is commonly diagnosed using serologic techniques and reverse transcription-polymerase chain reaction. This paper presents a novel plaque reduction neutralisation test (PRNT) for detecting antibodies to Brazilian hantavirus. Using PRNT, plaque detection was enhanced by adding 0.6% of dimethyl sulfoxide into the overlay culture medium of the infected cells. This procedure f...

  4. Anti-atherosclerotic effects of konjac

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2015-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-06-15

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

  6. [Lp-PLA2, a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques].

    Science.gov (United States)

    Bonnefont-Rousselot, D

    2016-05-01

    A chronic inflammation is involved in various stages of development of the atherosclerotic plaques. Among the emerging biomarkers of atherogenesis, the lipoprotein-associated phospholipase A2 (Lp-PLA2), formerly known as PAF-acetylhydrolase (McIntyre et al., 2009), hydrolyses the oxidized short chain phospholipids of low-density lipoproteins (LDL), thereby releasing pro-inflammatory mediators (lysophospholipids and oxidized fatty acids). Lp-PLA2, produced by monocytes/macrophages and T-lymphocytes, and mainly associated with LDL (Gazi et al., 2005), is predominantly expressed in the necrotic center of the atherosclerotic plaques and in the macrophage-rich areas (Kolodgie et al., 2006). It would have a predictive role of cardiovascular (CV) events in relation to the vulnerability of atherosclerotic plaques. Determination of Lp-PLA2 has been proposed in the assessment of the CV risk, to ensure a better stratification of populations at intermediate risk for targeted therapy (Davidson et al., 2008). Its proatherogenic role suggested that inhibition of its activity could ensure a better vascular protection in combination with cholesterol-lowering agents. Nevertheless, Lp-PLA2 is not yet a fully validated marker for use in daily clinical practice, especially since the studies using an inhibitor of Lp-PLA2 (darapladib) (STABILITY Investigators et al., 2014; O'Donoghue et al., 2014) did not show any reduction in coronary events. Lp-PLA2 could have a site-specific role in plaque inflammation and development (Fenning et al., 2015). High Lp-PLA2 activity could reflect a response to pro-inflammatory stress characteristic of atherosclerosis (Marathe et al., 2014). This presentation aims at clarifying the involvement of Lp-PLA2 in the pathophysiology of atherosclerosis, and at assessing its interest both as a biomarker for the onset of CV events and as a therapeutic target. PMID:26499399

  7. Elevated concentrations of pentraxin 3 are associated with coronary plaque vulnerability

    International Nuclear Information System (INIS)

    Inflammation is a critical contributing factor to the development and progression of atherosclerosis. Pentraxin 3 (PTX3) is produced abundantly in atherosclerotic lesions while C-reactive protein (CRP) is mainly produced in the liver. In this study, we investigated whether plasma levels of PTX3 might be a sensitive marker both for the severity of coronary artery disease and vulnerable plaques. Next, we determined whether assays for inflammatory molecules can be used to monitor the therapeutic effects of telmisartan on stabilization of vulnerable atherosclerotic plaques. We measured PTX3 concentrations in the peripheral and coronary sinus plasma of 40 patients with angina pectoris (AP) and 20 control subjects. Next, in 28 patients with AP, we determined the correlation between levels of inflammatory molecules and the computed tomography (CT) density of plaques as a quantitative index of plaque vulnerability. There was no significant difference in peripheral plasma PTX3 concentrations between patients with AP and control subjects, while coronary sinus plasma PTX3 concentrations were significantly higher in AP patients than control subjects. The concentrations of PTX3 in coronary sinus and peripheral plasma correlated with Gensini scores as an index of severity of coronary atherosclerosis. Interestingly, there was a significantly negative correlation between plasma PTX3 concentrations and CT density (r=-0.67, p<0.01). On the other hand, CT density did not correlate with the peripheral plasma concentrations of monocyte chemoattractant protein-1 (MCP-1) or high-sensitivity CRP (hsCRP). Furthermore, telmisartan treatment for 6 months decreased plasma concentrations of PTX3 but not those of MCP-1 or hsCRP in 12 patients with essential hypertension. Multivariate regression analysis revealed that changes in PTX3 levels were independent of blood pressure changes. PTX3 is likely more specific than hsCRP as an indicator of coronary plaque vulnerability that could lead to

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

    OpenAIRE

    Tang Bing; Li; Yang Dachun; Ma Shuangtao; Yang Yongjian

    2011-01-01

    Abstract Background Elevated plasma free fatty acid (FFA) levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36) is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36. Results We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs) treated with oleic acid (OA). We found that OA induces lipid accum...

  9. The relationship of hydroxyeicosatetraenoic acids and F2-isoprostanes to plaque instability in human carotid atherosclerosis

    OpenAIRE

    Mallat, Ziad; Nakamura, Tatsuji; Ohan, Jeanny; Lesèche, Guy; Tedgui, Alain; Maclouf, Jacques; Murphy, Robert C.

    1999-01-01

    Evidence for increased oxidant stress has been reported in human atherosclerosis. However, no information is available about the importance of in situ oxidant stress in relation to plaque stability. This information is relevant because the morbidity and mortality of atherosclerosis are essentially the consequences of acute ischemic syndromes due to unstable plaques. We studied 30 carotid atherosclerotic plaques retrieved by endarterectomy from 18 asymptomatic (stable plaques) and 12 symptomat...

  10. IVUS-Based FSI Models for Human Coronary Plaque Progression Study: Components, Correlation and Predictive Analysis

    OpenAIRE

    WANG, LIANG; Wu, Zheyang; Yang, Chun; Zheng, Jie; Bach, Richard; Muccigrosso, David; Billiar, Kristen; Maehara, Akiko; Mintz, Gary S; Tang, Dalin

    2014-01-01

    Atherosclerotic plaque progression is believed to be associated with mechanical stress conditions. Patient follow-up in vivo intravascular ultrasound coronary plaque data were acquired to construct fluid-structure interaction (FSI) models with cyclic bending to obtain flow wall shear stress (WSS), plaque wall stress (PWS) and strain (PWSn) data and investigate correlations between plaque progression measured by wall thickness increase (WTI), cap thickness increase (CTI), lipid depth increase ...

  11. High reproducibility of histological characterization by whole virtual slide quantification; an example using carotid plaque specimens.

    Directory of Open Access Journals (Sweden)

    Joyce E P Vrijenhoek

    Full Text Available Tissue biobanks are an important source for discovery and validation studies aiming for new proteins that are causally related with disease development. There is an increasing demand for accurate and reproducible histological characterization, especially for subsequent analysis and interpretation of data in association studies. We assessed reproducibility of one semiquantative and two quantitative methods for histological tissue characterization. We introduce a new automated method for whole digital slide quantification. Carotid atherosclerotic plaques were used to test reproducibility.50 atherosclerotic plaques that were obtained during carotid endarterectomy were analysed. For the semiquantitative analysis, 6 different plaque characteristics were scored in categories by two independent observers, and Cohen's κ was used to test intra- and interobserver reproducibility. The computer-aided method (assessed by two independent observers and automated method were tested on CD68 (for macrophages and α smooth muscle actin (for smooth muscle cells stainings. Agreement for these two methods (done on a continuous scale was assessed by intraclass correlation coefficients (ICCs.For the semiquantitative analysis, κ values ranged from 0.55 to 0.69 for interobserver variability, and were slightly higher for intraobserver reproducibility in both observers. The computer-aided method yielded intra- and interobserver ICCs between 0.6 and 0.9. The new automated method performed most optimal regarding reproducibility, with ICCs ranging from 0.92 to 0.97.The analysis of performance of three methods for histological slide characterization on carotid atherosclerotic plaques showed high precision and agreement in repeated measurements for the automated method for whole digital slide quantification. We suggest that this method can fulfill the need for reproducible histological quantification.

  12. Anti-atherosclerotic effects of konjac

    OpenAIRE

    Hidekatsu Yanai; Hiroki Adachi; Hisayuki Katsuyama; Hidetaka Hamasaki; Akahito Sako

    2015-01-01

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

  13. Development and Evaluation of Self-Applied Plaque Indices for Children.

    Science.gov (United States)

    Hunter, Harold G.; And Others

    This paper reports on one of the main goals of preventive dentistry, that is, encouraging children to remove plaque at least once a day. Two self-scoring systems were combined with two disclosants for a total of four experimental systems administered to 128 children. In the count method, the child counts the number of stained teeth; in the rating…

  14. Development of a novel plaque reduction neutralisation test for hantavirus infection

    Directory of Open Access Journals (Sweden)

    Michelly de Pádua

    2015-08-01

    Full Text Available In the Americas, hantaviruses cause severe cardiopulmonary syndrome (HCPS with a high fatality rate. Hantavirus infection is commonly diagnosed using serologic techniques and reverse transcription-polymerase chain reaction. This paper presents a novel plaque reduction neutralisation test (PRNT for detecting antibodies to Brazilian hantavirus. Using PRNT, plaque detection was enhanced by adding 0.6% of dimethyl sulfoxide into the overlay culture medium of the infected cells. This procedure facilitated clear visualisation of small plaques under the microscope and provided for easy and accurate plaque counting. The sera from 37 HCPS patients from the city of Ribeirão Preto, Brazil was evaluated for the Rio Mamoré virus (RIOMV using PRNT. Six samples exhibited neutralising antibodies; these antibodies exhibited a low titre. The low level of seropositive samples may be due to fewer cross-reactions between two different hantavirus species; the patients were likely infected by Araraquara virus (a virus that has not been isolated and RIOMV was used for the test. This assay offers a new approach to evaluating and measuring neutralising antibodies produced during hantavirus infections and it can be adapted to other hantaviruses, including viruses that will be isolated in the future.

  15. Development of an aptamer-conjugated fluorescent nanoprobe for MMP2

    Science.gov (United States)

    Han, Myoung-Eun; Baek, Sungmin; Kim, Hyun-Jung; Lee, Jung Hwan; Ryu, Sung-Ho; Oh, Sae-Ock

    2014-03-01

    Matrix metalloproteinase 2 (MMP2) plays critical roles in various diseases, such as atherosclerosis and cancer, and has been suggested to contribute to the instability of atherosclerotic plaque. To visualize MMP2 in pathologic tissues, we developed an aptamer targeting MMP2 protein by performing eight rounds of modified DNA systematic evolution of ligands by exponential enrichment (SELEX). The aptamer showed high affinity for MMP2 ( K d = 5.59 nM), precipitated MMP2, and detected MMP2 protein in pathological tissues such as atherosclerotic plaque and gastric cancer tissues. Furthermore, a MMP2 aptamer-conjugated fluorescent nanoprobe successfully visualized atherosclerotic plaques in apolipoprotein E (ApoE) knockout mice. These results suggest that the devised MMP2 aptamer could be useful for the development of various diagnostic tools.

  16. Early identification of atherosclerotic disease by noninvasive imaging.

    Science.gov (United States)

    Fuster, Valentin; Lois, Fátima; Franco, Manuel

    2010-06-01

    Cardiovascular disease (CVD) is the leading cause of death worldwide, and its prevalence is expected to increase further, which will be associated with a substantial economic burden. High-risk or vulnerable plaques and, indirectly, the burden of atherosclerotic disease, are responsible for most major cardiovascular events. Most of the current prevention strategies are focused on identifying and managing the established risk factors (smoking, hypertension, hypercholesterolemia, diabetes, obesity, physical inactivity) for atherosclerosis. Another opportunity for further characterizing the population at high CVD risk would be to measure the occurrence and progression of subclinical (asymptomatic) atherosclerotic burden. The detection of subclinical atherosclerosis and high-risk plaques, if proven to predict cardiovascular events, may enable the establishment of earlier control of CVD risk factors and help preventing CVD. In this Review, we address the potential progress in CVD prevention brought about by the use of noninvasive imaging techniques to identify subclinical atherosclerosis. PMID:20440291

  17. Molecular imaging of vulnerable atherosclerosis. Preclinical and clinical evaluation of nuclear tracers; Imagerie moleculaire de la plaque d'atherome vulnerable. Evaluation preclinique et clinique de traceurs radioactifs

    Energy Technology Data Exchange (ETDEWEB)

    Broisat, A.; Riou, L.M.; Dimastromatteo, J.; Pons, G.; Fagret, D.; Ghezzi, C. [Inserm U877, radiopharmaceutiques biocliniques, 38 - Grenoble (France); Grenoble Univ., 38 (France); Dimastromatteo, J. [ERAS Labo, 38 - Saint-Nazaire-les-Eymes (France)

    2009-02-15

    Atherosclerotic cardiovascular diseases (C.V.D.) are the leading cause of mortality worldwide, accounting for greater than 19.106 deaths annually. Despite major advances in the treatment of C.V.D., a high proportion of C.V.D. victims die suddenly while being apparently healthy, the great majority of these accidents being due to the rupture or erosion of a vulnerable coronary atherosclerotic plaque. Indeed, an acute heart attack is the first symptom of atherosclerosis in as much as 50% of individuals with severe disease. A non-invasive imaging methodology allowing the early detection of vulnerable atherosclerosis in selected individuals prior to the occurrence of any symptom would therefore be of great public health benefit. Nuclear imaging could potentially allow the identification of vulnerable patients by non-invasive scintigraphic imaging following administration of a radiolabeled tracer. The development of radiolabeled probes that specifically bind to and allow the in vivo imaging of vulnerable atherosclerotic plaques is therefore the subject of intense ongoing experimental and clinical research. Radiotracers targeted at the inflammatory process seem particularly relevant and promising. Recently, macrophage targeting allowed the experimental in vivo detection of atherosclerosis using either SPECT or PET imaging. A few tracers have also been evaluated clinically. Targeting of apoptosis and macrophage metabolism both allowed the imaging of vulnerable atherosclerotic plaques in the carotid vessels of patients. However, nuclear imaging of vulnerable plaques at the level of the coronary arteries remains a challenging issue because of the small size of atherosclerotic lesions and of their vicinity with blood and the circulating tracer activity. (authors)

  18. Human coronary plaque wall thickness correlated positively with flow shear stress and negatively with plaque wall stress: an IVUS-based fluid-structure interaction multi-patient study

    OpenAIRE

    Fan, Rui; Tang, Dalin; Yang, Chun; Zheng, Jie; Bach, Richard; WANG, LIANG; Muccigrosso, David; Billiar, Kristen; Zhu, Jian; Ma, Genshan; Maehara, Akiko; Mintz, Gary S

    2014-01-01

    Background Atherosclerotic plaque progression and rupture are believed to be associated with mechanical stress conditions. In this paper, patient-specific in vivo intravascular ultrasound (IVUS) coronary plaque image data were used to construct computational models with fluid-structure interaction (FSI) and cyclic bending to investigate correlations between plaque wall thickness and both flow shear stress and plaque wall stress conditions. Methods IVUS data were acquired from 10 patients afte...

  19. In vivo determination of arterial collagen synthesis in atherosclerotic rabbits

    International Nuclear Information System (INIS)

    Collagen and non-collagen protein synthesis rates were determined in vivo in tissues from rabbits fed a control or atherogenic diet supplemented with 2% peanut oil and 0.25% cholesterol for 4 months. Rabbits received a bolus intravenous injection of L-[3H]-proline (1.0 mCi/kg) and unlabeled L-proline (7 mmoles/kg) in 0.9% NaCl. Plasma proline specific activity decreased only 20% over 5 hr and was similar to the specific activity of free proline in tissues. Thoracic aortas from atherosclerotic rabbits exhibited raised plaques covering at least 75% of the surface. Thoracic intima plus a portion of the media (TIM) was separated from the remaining media plus adventitia (TMA). Dry delipidated weight, total collagen content, and collagen as a percent of dry weight were increased significantly in the TIM of atherosclerotic rabbits. Collagen synthesis rates and collagen synthesis as a percent of total protein synthesis were likewise increased both in the TIM and in the abdominal aortas. No differences from controls either in collagen content or collagen synthesis rates were observed in the TMA, lung or skin. These results demonstrate for the first time in vivo that formation of atherosclerotic plaques is associated with increased rates of collagen synthesis. Furthermore, as previously observed with incubations in vitro, collagen synthesis was elevated to a greater extent than noncollagen protein synthesis in atherosclerotic aortas from rabbits fed cholesterol plus peanut oil

  20. Effect of calcification on the mechanical stability of plaque based on a three-dimensional carotid bifurcation model

    OpenAIRE

    Wong Kelvin KL; Thavornpattanapong Pongpat; Cheung Sherman CP; Sun Zhonghua; Tu Jiyuan

    2012-01-01

    Abstract Background This study characterizes the distribution and components of plaque structure by presenting a three-dimensional blood-vessel modelling with the aim of determining mechanical properties due to the effect of lipid core and calcification within a plaque. Numerical simulation has been used to answer how cap thickness and calcium distribution in lipids influence the biomechanical stress on the plaque. Method Modelling atherosclerotic plaque based on structural analysis confirms ...

  1. IGF-1 Has Plaque-Stabilizing Effects in Atherosclerosis by Altering Vascular Smooth Muscle Cell Phenotype

    OpenAIRE

    von der Thüsen, Jan H; Borensztajn, Keren S.; Moimas, Silvia; van Heiningen, Sandra; Teeling, Peter; Van Berkel, Theo J. C.; Biessen, Erik A. L.

    2011-01-01

    Insulin-like growth factor-1 (IGF-1) signaling is important for the maintenance of plaque stability in atherosclerosis due to its effects on vascular smooth muscle cell (vSMC) phenotype. To investigate this hypothesis, we studied the effects of the highly inflammatory milieu of the atherosclerotic plaque on IGF-1 signaling and stability-related phenotypic parameters of murine vSMCs in vitro, and the effects of IGF-1 supplementation on plaque phenotype in an atherosclerotic mouse model. M1-pol...

  2. When to image carotid plaque inflammation with FDG PET/CT

    DEFF Research Database (Denmark)

    Græbe, Martin; Borgwardt, Lise; Højgaard, Liselotte; Sillesen, Henrik Hegaard; Kjær, Andreas

    2010-01-01

    Quantification of 18-fluorodeoxyglucose (FDG) uptake in inflamed high-risk carotid atherosclerotic plaques is challenged by the spatial resolution of positron emission tomography (PET) and luminal blood activity. Late acquisition protocols have been used to overcome these challenges to enhance th...... methods of FDG uptake in carotid artery plaques between early and late PET scans.......Quantification of 18-fluorodeoxyglucose (FDG) uptake in inflamed high-risk carotid atherosclerotic plaques is challenged by the spatial resolution of positron emission tomography (PET) and luminal blood activity. Late acquisition protocols have been used to overcome these challenges to enhance the...

  3. Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.

    Directory of Open Access Journals (Sweden)

    Sara Hägg

    Full Text Available BACKGROUND: The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric (14C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s to determine the average biological age of carotid plaques. METHODOLOGY/PRINCIPAL FINDING: The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for (14C content by accelerator mass spectrometry. The average plaque age (i.e. formation time was 9.6±3.3 years. All but two plaques had formed within 5-15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014. Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1-5. However, plaques in the lowest tercile of plaque age (most recently formed were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively, less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05, and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05 than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our results show, for the first time, that plaque age, as judge by relative incorporation of (14C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.

  4. The Myth of “The Vulnerable Plaque”: Transitioning from a Focus on Individual Lesions to Atherosclerotic Disease Burden for Coronary Artery Disease Risk Assessment

    Science.gov (United States)

    Arbab-Zadeh, Armin; Fuster, Valentin

    2014-01-01

    The cardiovascular science community has pursued the quest to identify vulnerable atherosclerotic plaque in patients for decades, hoping to prevent acute coronary events. However, despite major advancements in imaging technology that allow visualization of rupture-prone plaques, clinical studies have not demonstrated improved risk prediction compared to traditional approaches. Considering the complex relationship between plaque rupture and acute coronary event risk suggested by pathology studies and confirmed by clinical investigations, these results are not surprising. This review summarizes the evidence supporting a multifaceted hypothesis of the natural history of atherosclerotic plaque rupture. Managing patients at risk of suffering acute coronary events mandates a greater focus on the atherosclerotic disease burden, rather than on features of individual plaques. PMID:25601032

  5. Rate of Atherosclerotic Plaque Formation Predicts Cardiovascular Events in ESRD

    OpenAIRE

    Benedetto, Francesco Antonio; Tripepi, Giovanni; Mallamaci, Francesca; Zoccali, Carmine

    2008-01-01

    Carotid intima media thickness (IMT) is a strong, independent predictor of cardiovascular events in both the general population and among those with end-stage renal disease (ESRD), but it is unknown whether changes in IMT or other ultrasound-measured indicators of atherosclerosis over time provide additional prognostic information. The progression of atherosclerosis with carotid ultrasound was followed in a cohort of 135 ESRD patients, 103 of whom had a repeat ultrasound after 15 mo of follow...

  6. Atherosclerotic Vessel Changes in Sarcoidosis.

    Science.gov (United States)

    Tuleta, I; Pingel, S; Biener, L; Pizarro, C; Hammerstingl, C; Öztürk, C; Schahab, N; Grohé, C; Nickenig, G; Schaefer, C; Skowasch, D

    2016-01-01

    Sarcoidosis is a systemic granulomatous disease. Atherosclerosis is a chronic inflammatory vessel disease. The aim of our present study was to investigate whether sarcoidosis could be associated with increased risk of atherosclerotic vessel changes. Angiological analysis and blood tests were performed in 71 sarcoidosis patients and 12 matched controls in this prospective cross-sectional study. Specifically, angiological measurements comprised ankle brachial index (ABI), central pulse wave velocity (cPWV), pulse wave index (PWI), and duplex sonography of central and peripheral arteries. Sarcoidosis activity markers (angiotensin converting enzyme, soluble interleukin-2 receptor) and cardiovascular risk parameters such as cholesterol, lipoprotein(a), C-reactive protein, interleukin 6, fibrinogen, d-dimer, and blood count were analyzed in blood. We found no relevant differences in ABI, cPWV, and plaque burden between the sarcoidosis and control groups (1.10 ± 0.02 vs. 1.10 ± 0.02, 6.7 ± 0.5 vs. 6.1 ± 1.2, 53.7 % vs. 54.5 %, respectively). However, PWI was significantly higher in sarcoidosis patients (146.2 ± 6.8) compared with controls (104.9 ± 8.8), irrespectively of the activity of sarcoidosis and immunosuppressive medication. Except for increased lipoprotein(a) and d-dimer in sarcoidosis, the remaining cardiovascular markers were similar in both groups. We conclude that sarcoidosis is associated with increased pulse wave index, which may indicate an early stage of atherosclerosis. PMID:26820732

  7. Intracranial Atherosclerotic Disease

    Directory of Open Access Journals (Sweden)

    Maria Khan

    2011-01-01

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

  8. Dental plaque development on a hydroxyapatite disk in young adults observed by using a barcoded pyrosequencing approach

    OpenAIRE

    Toru Takeshita; Masaki Yasui; Yukie Shibata; Michiko Furuta; Yoji Saeki; Nobuoki Eshima; Yoshihisa Yamashita

    2015-01-01

    Dental plaque is a dynamic microbial biofilm ecosystem that comprises hundreds of species including difficult-to-cultivate bacteria. We observed the assembly of a plaque bacterial community through 16S rRNA gene analysis. Plaque samples that accumulated on a hydroxyapatite disk for 1, 2, 3, 4, 5, and 7 days with saliva on day 0 were collected from 19 young adults using a removable resin splint. Quantitative PCR analysis showed that the total bacterial amount gradually increased and reached a ...

  9. Acute non-atherosclerotic ST-segment elevation myocardial infarction in an adolescent with concurrent hemoglobin H-Constant Spring disease and polycythemia vera

    Directory of Open Access Journals (Sweden)

    Ekarat Rattarittamrong

    2015-09-01

    Full Text Available Thrombosis is a major complication of polycythemia vera (PV and also a well-known complication of thalassemia. We reported a case of non-atherosclerotic ST-segment elevation myocardial infarction (STEMI in a 17- year-old man with concurrent post-splenectomized hemoglobin H-Constant Spring disease and JAK2 V617F mutation-positive PV. The patient initially presented with extreme thrombocytosis (platelet counts greater than 1,000,000/μL and three months later developed an acute STEMI. Coronary artery angiography revealed an acute clot in the right coronary artery without atherosclerotic plaque. He was treated with plateletpheresis, hydroxyurea and antiplatelet agents. The platelet count decreased and his symptoms improved. This case represents the importance of early diagnosis, awareness of the increased risk for thrombotic complications, and early treatment of PV in patients who have underlying thalassemia with marked thrombocytosis.

  10. Plaque characterization in ex vivo MRI evaluated by dense 3D correspondence with histology

    Science.gov (United States)

    van Engelen, Arna; de Bruijne, Marleen; Klein, Stefan; Verhagen, Hence; Groen, Harald; Wentzel, Jolanda; van der Lugt, Aad; Niessen, Wiro

    2011-03-01

    Automatic quantification of carotid artery plaque composition is important in the development of methods that distinguish vulnerable from stable plaques. MRI has shown to be capable of imaging different components noninvasively. We present a new plaque classification method which uses 3D registration of histology data with ex vivo MRI data, using non-rigid registration, both for training and evaluation. This is more objective than previously presented methods, as it eliminates selection bias that is introduced when 2D MRI slices are manually matched to histological slices before evaluation. Histological slices of human atherosclerotic plaques were manually segmented into necrotic core, fibrous tissue and calcification. Classification of these three components was voxelwise evaluated. As features the intensity, gradient magnitude and Laplacian in four MRI sequences after different degrees of Gaussian smoothing, and the distances to the lumen and the outer vessel wall, were used. Performance of linear and quadratic discriminant classifiers for different combinations of features was evaluated. Best accuracy (72.5 +/- 7.7%) was reached with the linear classifier when all features were used. Although this was only a minor improvement to the accuracy of a classifier that only included the intensities and distance features (71.6 +/- 7.9%), the difference was statistically significant (paired t-test, p<0.05). Good sensitivity and specificity for calcification was reached (83% and 95% respectively), however, differentiation between fibrous (sensitivity 85%, specificity 60%) and necrotic tissue (sensitivity 49%, specificity 89%) was more difficult.

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

    NARCIS (Netherlands)

    Valk, van der Fleur M.; Wijk, van Diederik F.; Lobatto, Mark E.; Verberne, Hein J.; Storm, Gert; Willems, Martine C.M.; Legemate, Dink A.; Nederveen, Aart J.; Calcagno, Claudia; Mani, Venkatesh; Ramachandran, Sarayu; Paridaans, Maarten P.M.; Otten, Maarten J.; Dallinga-Thie, Geesje M.; Fayad, Zahi A.; Nieuwdorp, Max; Schulte, Dominik M.; Metselaar, Josbert M.; Mulder, Willem J.M.; Stroes, Erik S.G.

    2015-01-01

    Drug delivery to atherosclerotic plaques via liposomal nanoparticles may improve therapeutic agents’ risk–benefit ratios. Our paper details the first clinical studies of a liposomal nanoparticle encapsulating prednisolone (LN-PLP) in atherosclerosis. First, PLP’s liposomal encapsulation improved its

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Novel hybrid 18-fluoro-deoxy-D-glucose ((18)F-FDG) based positron emission tomography (PET) and magnetic resonance imaging (MRI) has shown promise for characterization of atherosclerotic plaques clinically. The purpose of this study was to evaluate the method in a pre-clinical model of diet-induc...

  13. Differential X-ray phase contrast tomography of Alzheimer plaques in mouse models: perspectives for drug development and clinical imaging techniques

    International Nuclear Information System (INIS)

    Alzheimer's disease (AD) is a looming threat on an ever-ageing population, with devastating effects on the human intellect. A particular characteristic lesion — the extracellular amyloid plaque — accumulates in the brain of AD patients during the course of the disease, and could therefore be used to monitor the progression of the disease, years before the first neurological symptoms appear. In addition, strategies for drug intervention in AD are often based on amyloid reduction, since amyloid plaques are hypothesized to be involved in a chain of reactions leading to the death of neurons. Developments in both fields would benefit from a microscopic technique that is capable of single plaque imaging, ideally in 3D. While such a non-destructive, single-plaque imaging technique does not yet exist for humans, it has been recently shown that synchrotron based differential X-ray phase contrast imaging can be used to visualize individual plaques at μm resolution in mouse models of AD ex-vivo. This method, which relies on a grating interferometer to measure refraction angles induced by fluctuations in the refractive index, yields a precise three-dimensional distribution of single plaques. These data could not only improve the understanding of the evolution of AD or the effectiveness of drugs, but could also help to improve reliable markers for current and future non-invasive clinical imaging techniques. In particular, validation of PET markers with small animal models could be rapidly carried out by co-registration of PET and DPC signals.

  14. Nanoparticle-Enhanced Near Infrared Fluorescence Imaging of Atheroma Detects Thrombosis-Prone Plaques Prior to Rupture

    OpenAIRE

    Stein-Merlob, Ashley F.

    2015-01-01

    Introduction: Acute coronary syndromes - including unstable angina, acute myocardial infarction and sudden death - are primarily due to sudden luminal thrombosis from disruption of an atherosclerotic plaque. It has been established that inflammation plays an important role in atherogenesis and the destabilization of plaques. However, the role of inflammation in catalyzing plaque rupture is incompletely understood. Here, we experimentally investigated the in vivo spatial distribution of a nove...

  15. Relationship between Enhanced Intensity of Contrast Enhanced Ultrasound and Microvessel Density of Aortic Atherosclerostic Plaque in Rabbit Model

    OpenAIRE

    Xiangdong You; Pintong Huang; Chao Zhang; Minghui Wang; Ying Zhang; Yurong Hong; Shumei Wei; Chunmei Liu; Zhaoxia Pu; Jianmin Zhang; Shuyuan Chen

    2014-01-01

    The aim of this study was to evaluate the relationship between enhanced intensity of contrast enhanced ultrasound and microvessel density of aortic atherosclerotic plaque in rabbit model. The abdominal aortas of thirty-six male New Zealand rabbits were damaged by balloon expansion and the animals were then fed a high fat diet for 12 weeks. Twenty-seven plaques on the near aortic wall were detected using conventional ultrasound examination. The maximum thickness of each plaque was recorded. CE...

  16. Characterization of plaque in the internal carotid artery. Comparison neuroradiological findings with pathological findings

    International Nuclear Information System (INIS)

    We evaluate the morphology of the carotid plaque using echogram, CT scan and MRI and compare those neuroradiological findings with histological findings of the plaque. We evaluated 14 cases operated with carotid endoarterectomy for carotid stenosis. We estimated the findings of the echogram, enhanced CT scan and black blood MRI (BB MRI), in comparison with the histological findings of the carotid plaque. Echogram, enhanced CT scan and MRI clearly demonstrated the plaque in cervical carotid stenosis. In most cases, echograms could show the plaque, but in some cases could not due to the back shadow caused by plaque calcification. Enhanced CT scan clearly demonstrated the calcification and the neovasculization in plaque. BB MRI clearly showed the carotid plaque. Low-intensity lesions in T1 and T2 weighted images showed hard and fibrous plaque. High-intensity lesions in T1 and T2 weighted images showed soft plaque with lipoprotein and/or hemorrhage. This study demonstrates the potential of a systemic approach to atherosclerotic plaque with enhanced CT scan and BB MRI compared with histological findings of the carotid plaque. These estimations elucidate the growth mechanism of carotid plaque. (author)

  17. Nanoparticle uptake by macrophages in vulnerable plaques for atherosclerosis diagnosis.

    Science.gov (United States)

    Melzer, Susanne; Ankri, Rinat; Fixler, Dror; Tarnok, Attila

    2015-11-01

    The composition of atherosclerotic (AS) plaques is crucial concerning rupture, thrombosis and clinical events. Two plaque types are distinguished: stable and vulnerable plaques. Vulnerable plaques are rich in inflammatory cells, mostly only M1 macrophages, and are highly susceptible to rupture. These plaques represent a high risk particularly with the standard invasive diagnosis by coronary angiography. So far there are no non-invasive low-risk clinical approaches available to detect and distinguish AS plaque types in vivo. The perspective review introduces a whole work-flow for a novel approach for non-invasive detection and classification of AS plaques using the diffusion reflection method with gold nanoparticle loaded macrophages in combination with flow and image cytometric analysis for quality assurance. Classical biophotonic methods for AS diagnosis are summarized. Phenotyping of monocytes and macrophages are discussed for specific subset labelling by nanomaterials, as well as existing studies and first experimental proofs of concept for the novel approach are shown. In vitro and in vivo detection of NP loaded macrophages (MΦ). Different ways of MΦ labelling include (1) in vitro labelling in suspension (whole blood or buffy coat) or (2) labelling of short-term MΦ cultures with re-injection of MΦ-NP into the animal to detect migration of the cells in the plaques and (3) in vivo injection of NP into the organism. PMID:26110589

  18. Aterofisiol® in carotid plaque evolution

    Directory of Open Access Journals (Sweden)

    Amato B

    2015-07-01

    Full Text Available Bruno Amato,1,2,* Rita Compagna,1,2,* Maurizio Amato,2 Luca Gallelli,3 Stefano de Franciscis,1,4,* Raffaele Serra1–4,*1Interuniversity Center of Phlebolymphology (CIFL, International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, 2Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, 3Department of Health Sciences, University of Catanzaro, Catanzaro, 4Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy*These authors contributed equally to this workBackground: In patients with carotid stenosis, the risk of plaque rupture is related to the composition of the atherosclerotic plaque rather than to its magnitude. In this regard, we evaluated the effects of a supplement, Aterofisiol,® containing omega-3 (EPA [eicosapen acid] DHA [docosahexaenoic acid], vitamin K2, vitamin B6, vitamin B12, oligomeric proanthocyanidins (OPC and resveratrol on the composition of atherosclerotic plaque and on neurological symptoms in patients with carotid stenosis undergoing carotid endarterectomy.Methods: The study was randomized, prospective, and double-blinded. Eligible patients were of both sexes, with carotid stenosis >70% who underwent endarterectomy. Enrolled patients were randomly allocated to receive either one tablet of acetylsalicylic acid 100 mg (Cardioaspirin® + one tablet of Aterofisiol every 24 hours or one tablet of Cardioaspirin + one tablet of placebo every 24 hours. Each treatment was started 30 days before the surgery and was stopped 5 days before the surgery. The plaques were removed “en bloc” using standard surgical technique.Results: During the study period, 214 patients (135 men and 79 women were enrolled for intent-to-treat and randomized in two groups: Group A: 107 patients (68 men and 39 women were treated with Cardioaspirin + Aterofisiol. Group B: 107 patients (67 men and 40

  19. Spontaneous and Procedural Plaque Embolisation in Native Coronary Arteries: Pathophysiology, Diagnosis, and Prevention

    Directory of Open Access Journals (Sweden)

    Giovanni Luigi De Maria

    2013-01-01

    Full Text Available The detachment of atherothrombotic material from the atherosclerotic coronary plaque and downstream embolisation is an underrecognized phenomenon and it causes different degrees of impairment of the coronary microcirculation. During treatment of obstructive atherosclerotic plaque by percutaneous coronary intervention (PCI distal embolisation (DE is considered to be inevitable and it is associated with potential clinical and prognostic implications. This review aims to assess the main aspects of both spontaneous and procedural DE, analyze their different pathophysiology, provide specific insights on the main diagnostic tools for their identification, and finally focus on the main strategies for their treatment and prevention.

  20. Local blood pressure associates with the degree of luminal stenosis in patients with atherosclerotic disease in the middle cerebral artery

    OpenAIRE

    Jiang, Yuanliang; Peng, Wenjia; Teng, Zhongzhao; Gillard, Jonathan H.; Hong, Bo; Liu, Qi; Lu, Jianping

    2016-01-01

    The mechanism underlying atherosclerotic ischemic events within the middle cerebral artery (MCA) is unclear. High structural stress induced by blood pressure might be a potential aetiology as plaque rupture occurs when such mechanical loading exceeds its material strength. To perform reliable analyses quantifying the mechanical loading within a plaque, the local blood pressure is needed. However, data on MCA blood pressure is currently lacking. In this study, the arterial pressure proximal to...

  1. [Coronary atherosclerosis and progression to unstable plaques : Histomorphological and molecular aspects].

    Science.gov (United States)

    Wohlschlaeger, Jeremias; Bertram, S; Theegarten, D; Hager, T; Baba, H A

    2015-09-01

    Atherosclerosis causes clinical symptoms through luminal narrowing by stenosis or by precipitating thrombi that obstruct blood flow to the myocardium (coronary artery disease), central nervous system (ischemic stroke) or lower extremities (peripheral vascular disease). The most common of these manifestations of atherosclerosis is coronary artery disease, clinically presenting as either stable angina or acute coronary syndromes. Atherosclerosis is a mainly lipoprotein-driven disease, which is associated with the formation of atherosclerotic plaques at specific sites of the vascular system through inflammation, necrosis, fibrosis and calcification. In most cases, plaque rupture of a so-called thin-cap fibroatheroma leads to contact of the necrotic core material of the underlying atherosclerotic plaque with blood, resulting in the formation of a thrombus with acute occlusion of the affected (coronary) artery. The atherosclerotic lesions that can cause acute coronary syndromes by formation of a thrombotic occlusion encompass (1) thin-cap fibroatheroma, (2) plaque erosion and (3) so-called calcified nodules in calcified and tortuous arteries of aged individuals. The underlying pathomechanisms remain incompletely understood so far. In this review, the mechanisms of atherosclerotic plaque initiation and progression are discussed. PMID:26216542

  2. Short-term administration of basic fibroblast growth factor enhances coronary collateral development without exacerbating atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic rabbits with acute myocardial infarction.

    Science.gov (United States)

    Zhang, Chunxiang; Yang, Jian; Feng, Jianzhang; Jennings, Lisa K

    2002-08-01

    We evaluated the effect of basic fibroblast growth factor (bFGF) on the extent of atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic animals with acute myocardial infarction (AMI). Fifty-six rabbits were fed a 1% cholesterol diet. Balloon injury of iliac arteries and experimental acute myocardial infarction were induced in the same animals. Rabbits were then randomized to a bFGF group (20 pg/day, intravenously) or a control group (intravenous saline solution). The beneficial effects of bFGF on cardiac function, infarct size, and collateral vessel development, and the possible effect on vasoproliferation of balloon-injured vessels, were measured after 1 and 2 weeks. The extent of atherosclerosis was measured after 1, 2, and 4 weeks. Our results showed that bFGF significantly reduced infarct size and increased collateral-vessel density (P atherosclerosis and the vasoproliferation in chronic atherosclerotic vessels induced by balloon injury and cholesterol diet were not significantly different between the two groups. Our results suggest that short-term treatment with bFGF enhances collateral development and produces maximum therapeutic benefits without exacerbating atherosclerosis and cell proliferation in stenotic vessels after AMI in atherosclerotic rabbits. PMID:12228768

  3. Bacteria Present in Carotid Arterial Plaques Are Found as Biofilm Deposits Which May Contribute to Enhanced Risk of Plaque Rupture

    OpenAIRE

    Lanter, Bernard B.; Sauer, Karin; Davies, David G

    2014-01-01

    ABSTRACT Atherosclerosis, a disease condition resulting from the buildup of fatty plaque deposits within arterial walls, is the major underlying cause of ischemia (restriction of the blood), leading to obstruction of peripheral arteries, congestive heart failure, heart attack, and stroke in humans. Emerging research indicates that factors including inflammation and infection may play a key role in the progression of atherosclerosis. In the current work, atherosclerotic carotid artery explants...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Pregnancy-associated plasma protein-A (PAPP-A) increases local IGF-I bioavailability through cleavage of inhibitory IGF binding protein (IGFBP)-4 in a variety of systems, including the cardiovascular system. To test the hypothesis that expression of PAPP-A promotes the development of atherosclero......Pregnancy-associated plasma protein-A (PAPP-A) increases local IGF-I bioavailability through cleavage of inhibitory IGF binding protein (IGFBP)-4 in a variety of systems, including the cardiovascular system. To test the hypothesis that expression of PAPP-A promotes the development of...

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  6. CO2 vascular anastomosis of atherosclerotic and calcified arteries

    Science.gov (United States)

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

    1990-06-01

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

  7. Carotid endarterectomy for atherosclerotic carotid artery stenosis

    International Nuclear Information System (INIS)

    Several randomized controlled trials (RCTs) have demonstrated carotid endarterectomy (CEA) to be more beneficial for the prevention of recurrent or first-ever ischemic stroke than treatment with antiplatelet agents in patients with moderate-severe stenosis of the cervical internal carotid artery. CEA is the standard treatment for such lesions; however, other RCTs have demonstrated carotid artery stenting (CAS) with a protective device to be comparable to CEA in patients with or without radiological or medical high-risks for CEA, although the selection criteria among these treatments have not yet been established in clinical practice. This review compares the results of RCTs valuating the superiority of CEA over medical treatment or CAS, preoperative examination, procedures of CEA, perioperative management and complications, long-term results, and indications for CEA based on the currently available evidence-based publications. A preoperative evaluation of the patients' medical condition, including atherosclerosis, is therefore important to minimize the perioperative complications of CEA, because myocardial infarction during the perioperative period is frequently observed in patients undergoing CEA. A through radiological examination such as plaque imaging is essential for selecting appropriate treatment strategies involving revascularization or medical treatment for atherosclerotic carotid artery stenosis. In addition, the surgical indications, particularly for asymptomatic lesions, should be carefully considered in light of the recent improvements in medical treatments including antihypertensive agents and statins. (author)

  8. Plaque Ablation by Excimer Laser Irradiation Using a Movable Energy-Transmitting Device

    OpenAIRE

    Laufer, Günther; Wollenek, Gregor; Stangl, Günther; Klepetko, Walter; Fasol, Roland; Zilla, Peter; Wolner, Ernst

    1987-01-01

    During the past 2 years, excimer laser energy has been shown to provide a highly suitable type of atherosclerotic plaque ablation, especially in small-diameter vessels such as coronary or crural arteries. Nevertheless, transmission of far-ultraviolet pulsed laser power has remained a major problem in animal studies and clinical trials.

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

    Science.gov (United States)

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

    2009-01-01

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

  10. Evaluation of periodontal index of gingival and plaque with dental crowding in development of gingivits in children and adolescents

    Directory of Open Access Journals (Sweden)

    Maria Dalva de Souza SCHROEDER

    2004-11-01

    Full Text Available The aim of this study was to evaluate the correlation between dentalcrowding and the periodontal index of gingival and plaque indevelopment of gingivits in children and adolescents in the age groupof 7 to 15 years old, as a mean to prevent the periodontal disease that according to literature, begins precociously during childhood anddevelops during adult age. After verification of the conditions through utilization of those indexes, it was possible to conclude that gingivitis was present in practically 100% of the examined individuals. There is a positive correlation between the presence of dental plaque and gum inflammation stages, it was not possible to establish a definite correlation between dental crowding and gingivitis.

  11. High shear stress influences plaque vulnerability Part of the data presented in this paper were published in Stroke 2007;38:2379-81.

    OpenAIRE

    Groen, H. C.; Gijsen, F. J. H.; van der Lugt, A.; Ferguson, M. S.; Hatsukami, T.S.; Yuan, C; van der Steen, A. F. W.; Wentzel, J.J.

    2008-01-01

    Shear stress of the blood at the vessel wall plays an important role in many processes in the cardiovascular system primarily focused on the regulation of vessel lumen and wall dimensions. There is ample evidence that atherosclerotic plaques are generated at low shear stress regions in the cardiovascular system, while high shear stress regions are protected. In the course of plaque progression, advanced plaques start to encroach into the lumen, and thereby start to experience high shear stres...

  12. Atherosclerotic Calcification Detection: A Comparative Study of Carotid Ultrasound and Cone Beam CT

    OpenAIRE

    Fisnik Jashari; Pranvera Ibrahimi; Elias Johansson; Jan Ahlqvist; Conny Arnerlöv; Maria Garoff; Eva Levring Jäghagen; Per Wester; Michael Y. Henein

    2015-01-01

    BACKGROUND AND AIM: Arterial calcification is often detected on ultrasound examination but its diagnostic accuracy is not well validated. The aim of this study was to determine the accuracy of carotid ultrasound B mode findings in detecting atherosclerotic calcification quantified by cone beam computed tomography (CBCT). METHODS: We analyzed 94 carotid arteries, from 88 patients (mean age 70 ± 7 years, 33% females), who underwent pre-endarterectomy ultrasound examination. Plaques with high ec...

  13. Prediction of Viscoelastic Behavior of Blood Flow in Plaque Deposited Capillaries

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    Muhammad Anwar Solangi

    2012-10-01

    Full Text Available The paper investigates the viscoelastic behaviour of blood over low value of elasticity, to analyse the influence of inertia in the presence of elasticity. For viscoelastic fluids shear-thinning and strainsoftening PTT (Phan-Thien/Tanner constitutive model is employed to identify the influence of elasticity. The computational method adopted is based on a finite element semi-implicit time stepping Taylor- Galerkin/pressure-correction scheme. Simulations are conducted via atherosclerotic vessels along with various percentages of deposition at distinct values of Reynolds numbers. The numerical simulations are performed for recirculation flow structure and development of recirculation length to investigate the impact of atherosclerosis on partially blocked plaque deposited vessels.

  14. Evaluation of periodontal index of gingival and plaque with dental crowding in development of gingivits in children and adolescents

    OpenAIRE

    Maria Dalva de Souza SCHROEDER; Gerson Luis Ulema RIBEIRO

    2004-01-01

    The aim of this study was to evaluate the correlation between dentalcrowding and the periodontal index of gingival and plaque indevelopment of gingivits in children and adolescents in the age groupof 7 to 15 years old, as a mean to prevent the periodontal disease that according to literature, begins precociously during childhood anddevelops during adult age. After verification of the conditions through utilization of those indexes, it was possible to conclude that gingivitis was present in pr...

  15. Noninvasive carotid plaque characterization by black blood MRI

    International Nuclear Information System (INIS)

    Management of atherosclerotic carotid arteries requires both plaque characterization and determination of the degree of stenosis, especially when carotid stenting (GAS) is being considered for severe carotid stenosis. Recent studies have demonstrated that high-resolution MRI can identify plaque components, such as the lipid-rich necrotic core, intraplaque hemorrhage, fibrous tissue, and the calcification present in human carotid atherosclerosis. The purpose of this study was to assess the feasibility of black blood MRI (BB-MRI) for accurately identifying the plaque components in vivo. Twenty-six consecutive patients scheduled for carotid endarterectomy (CEA) underwent a BB-MRI examination within 2 weeks before the surgical procedure using a 1.5-T Philips scanner with a protocol that generated 2 contrast weightings (T1 and T2). The MR images were acquired using cardiac gating to minimize motion artifact and fat suppression to reduce MR signals from subcutaneous fatty tissue. The plaque evaluations obtained by BB-MRI were compared with the intra-operative video recordings, the excised specimens, and the histological sections. With BB-MRI, the combination of the signal intensities in the T1- and T2- weighted images for each component (lipid deposits, intra-plaque hemorrhage, fibrous plaque, and calcification) showed findings that corresponded with the excised specimens. Complex morphological features could also be assessed by BB-MRI. BB-MRI is a useful method for noninvasively imaging and characterizing atherosclerotic carotid arteries. This MRI technique can provide valuable information that can be used to decide whether to perform a CEA or a GAS in patients with severe carotid stenosis. Furthermore, BB-MRI appears to be a useful tool for the investigation of the pathogenesis and natural history of carotid atherosclerosis. (author)

  16. Evaluation of Carotid Plaque Using Ultrasound Imaging

    Science.gov (United States)

    2016-01-01

    Traditional risk factors for predicting of cardiovascular disease are not always effective predictors for development of cardiovascular events. This review summarizes several newly developed noninvasive imaging techniques for evaluating carotid plaques and their role in cardiovascular disease risk.

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

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    Raghav Oberoi

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

  18. The effects of plaque morphology and material properties on peak cap stress in human coronary arteries.

    Science.gov (United States)

    Akyildiz, Ali C; Speelman, Lambert; Nieuwstadt, Harm A; van Brummelen, Harald; Virmani, Renu; van der Lugt, Aad; van der Steen, Anton F W; Wentzel, Jolanda J; Gijsen, Frank J H

    2016-01-01

    Heart attacks are often caused by rupture of caps of atherosclerotic plaques in coronary arteries. Cap rupture occurs when cap stress exceeds cap strength. We investigated the effects of plaque morphology and material properties on cap stress. Histological data from 77 coronary lesions were obtained and segmented. In these patient-specific cross sections, peak cap stresses were computed by using finite element analyses. The finite element analyses were 2D, assumed isotropic material behavior, and ignored residual stresses. To represent the wide spread in material properties, we applied soft and stiff material models for the intima. Measures of geometric plaque features for all lesions were determined and their relations to peak cap stress were examined using regression analyses. Patient-specific geometrical plaque features greatly influence peak cap stresses. Especially, local irregularities in lumen and necrotic core shape as well as a thin intima layer near the shoulder of the plaque induce local stress maxima. For stiff models, cap stress increased with decreasing cap thickness and increasing lumen radius (R = 0.79). For soft models, this relationship changed: increasing lumen radius and increasing lumen curvature were associated with increased cap stress (R = 0.66). The results of this study imply that not only accurate assessment of plaque geometry, but also of intima properties is essential for cap stress analyses in atherosclerotic plaques in human coronary arteries. PMID:26237279

  19. A new inexpensive customized plaque for choroidal melanoma iodine-125 plaque therapy

    International Nuclear Information System (INIS)

    The authors have developed a new inexpensive precious metal alloy plaque for use in customized iodine-125 plaque therapy. Each plaque is formed from two flat circular gold/palladium foils which are used in dental crown work. Using a simple manual mechanism, the two forms are stamped over a customized acrylic die shaped to the dimensions of the tumor base plus a 2-mm margin. Completed plaques consist of a back wall, a 2-mm side wall, and a 1.5-mm wide lip with holes for suture placement. Advantages include: simple construction from inexpensive components, customized shape, and iodine seeds that are readily visible on plane radiographs

  20. Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition on serum matrix metalloproteinase-13 and tissue inhibitor matrix metalloproteinase-1 levels as a sign of plaque stabilization.

    Science.gov (United States)

    Cevik, Cihan; Otahbachi, Mohammad; Nugent, Kenneth; Warangkana, Chokesuwattanaskul; Meyerrose, Gary

    2008-12-01

    Atherosclerotic plaques are composed of a lipid rich core, which is covered by a collagen rich fibrous cap. Rupture of the atherosclerotic plaque with superimposed thrombosis is the main cause of acute coronary syndromes, including acute myocardial infarction and unstable angina. The stability of the plaque depends on its collagen content; degradation of the collagen leads to a vulnerable plaque that is prone to rupture. Recent studies have demonstrated a critical role for matrix metalloproteinases (MMPs) in the degradation of the collagen content and the reduction of mechanical stability of the atherosclerotic plaques. Increased expression of various MMPs has been shown in the tissue sections of atherosclerotic plaques. The increased expression of MMPs in the atheroma also leads to increased MMP levels in the circulation. The cholesterol lowering drugs - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) - decrease the tissue expression of various MMPs in atheromatous plaques by attenuating the inflammatory process that promotes MMP expression during the course of atherosclerosis. However, the effect of statin treatment on the serum levels of MMP-13, which has a critical role in the initiation of collagen degradation, is unknown. On the basis of these previous studies, we discuss the need for studies on the effect of statin treatment on the serum levels of MMP-13 and tissue inhibitor of matrix metalloproteinase (TIMP-1) levels in hypercholesterolemic patients. PMID:19001938

  1. Endothelial tyrosine kinase receptor B prevents VE-cadherin cleavage and protects against atherosclerotic lesion development in ApoE−/− mice

    OpenAIRE

    Jiang, Hong; Huang, Shuhong; Li, Xinyun; Li, Xian; Huang, ShanYing; Zhang, Yun; Chen, Zhe-Yu

    2015-01-01

    Tyrosine kinase receptor B (TrkB) is a high-affinity receptor for brain-derived neurotrophic factor (BDNF). In addition to its nervous system functions, TrkB is also expressed in the aortic endothelium. However, the effects of endothelial TrkB signaling on atherosclerosis remained unknown. Immunofluorescence analysis revealed that TrkB expression is downregulated in the endothelium of atherosclerotic lesions from ApoE−/− mice compared with the atheroma-free aorta of WT mice. Endothelial TrkB ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-01-01

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

  3. The analysis of the connection between plaque morphology of the asymptomatic carotid stenosis and ischemic brain lesions

    OpenAIRE

    Milošević Đorđe; Pasternak Janko; Popović Vladan; Nikolić Dragan; Milošević Pavle; Manojlović Vladimir

    2013-01-01

    Background/Aim. A certain percentage of patients with asymptomatic carotid stenosis have an unstable carotid plaque. For these patients it is possible to register by modern imaging methods the existence of lesions of the brain parenchyma - the silent brain infarction. These patients have a greater risk of ischemic stroke. The aim of this study was to analyze the connection between the morphology of atherosclerotic carotid plaque in patients with asymptomatic carotid stenosis and the man...

  4. Efecto inhibitorio en placa microbiana y propiedades antibacterianas de enjuagatorios de clorhexidina The effects of a chlorhexidine rinses on the development of plaque and antibacterial

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    Ismael Yevenes L

    2003-04-01

    digluconate of chlorhexidine. The effect on 24-h plaque regrowth were measured using of plaque area and plaque index in 3 double-blind studies in 20 subjects. For chlorhexidine concentration studies, sampIes all with different date of elaboration, were employed. The assessment of chlorhexidine was performed by HPLC chromatography. Microbicidal properties were measured by an inhibition assay of development of: Streptococcus mutans, Actinomyces viscosus and Candida albicans. Not significant differences plaque reformed after using the three chlorhexidine mouthwashes but less plaque developed whit the chlorhexidine compared with control. The chlorhexidine concentration were 0.1174%, 0.1168% and 0.091% for A, B and C samples respectively, stability values after 16 months of elaboration respectively. Thus, A and B mouthwashes had normal values of chlorhexidine, while that, for C it would be below its declaimed value. The most dated samples of mouthrinses had microbicidal activity against the tested micro-organisms. The inactivation time of bacterial growth was lesser or equal to 30 seconds. The methodologies applied allow to determine the effectiveness of such mouthrinses with different chlorhexidine concentration, when the results clearly suggests that 0.1 % chlorhexidine is enough to get antiplaque and antimicrobial activity, when used in mouthwashes, not been necessary concentrations more high in the mouthrinses

  5. Morphology of atherosclerotic coronary arteries

    Science.gov (United States)

    Holme, Margaret N.; Schulz, Georg; Deyhle, Hans; Hieber, Simone Elke; Weitkamp, Timm; Beckmann, Felix; Herzen, Julia; Lobrinus, Johannes A.; Montecucco, Fabrizio; Mach, François; Zumbuehl, Andreas; Saxer, Till; Müller, Bert

    2012-10-01

    Atherosclerosis, the narrowing of vessel diameter and build-up of plaques in coronary arteries, leads to an increase in the shear stresses present, which can be used as a physics-based trigger for targeted drug delivery. In order to develop appropriate nanometer-size containers, one has to know the morphology of the critical stenoses with isotropic micrometer resolution. Micro computed tomography in absorption and phase contrast mode provides the necessary spatial resolution and contrast. The present communication describes the pros and cons of the conventional and synchrotron radiation-based approaches in the visualization of diseased human and murine arteries. Using registered datasets, it also demonstrates that multi-modal imaging, including established histology, is even more powerful. The tomography data were evaluated with respect to cross-section, vessel radius and maximal constriction. The average cross-section of the diseased human artery (2.31 mm2) was almost an order of magnitude larger than the murine one (0.27 mm2), whereas the minimal radius differs only by a factor of two (0.51 mm versus 0.24 mm). The maximal constriction, however, was much larger for the human specimen (85% versus 49%). We could also show that a plastic model used for recent experiments in targeted drug delivery represents a very similar morphology, which is, for example, characterized by a maximal constriction of 82%. The tomography data build a sound basis for flow simulations, which allows for conclusions on shear stress distributions in stenosed blood vessels.

  6. CD105 positive neovessels are prevalent in early stage carotid lesions, and correlate with the grade in more advanced carotid and coronary plaques

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    Luque Ana

    2009-09-01

    Full Text Available Abstract Background Previous studies have demonstrated that expression of CD105 is a sensitive marker and indicator of endothelial cell/microvessel activation and proliferation in aggressive solid tumour growth and atherosclerotic plaque lesions. Since intimal neovascularization contributes significantly to subsequent plaque instability, haemorrhage and rupture. Methods We have used immunohistochemical analysis to investigate the expression of CD105-positive vessels in both large (carotid and medium calibre (coronary and middle cerebral artery, MCAs diseased vessels in an attempt to identify any correlation with plaque growth, stage and complication/type. Results Here we show, that carotid arteries expressed intimal neovascularization associated with CD105-positive endothelial cells, concomitant with increased inflammation in early stage lesions, preatheroma (I-III whilst they were not present in coronary plaques of the same grade. Some of these CD105-positive neovessels were immature, thin walled and without smooth muscle cell coverage making them more prone to haemorrhage and rupture. In high-grade lesions, neovessel proliferation was similar in both arterial types and significantly higher numbers of CD105-positive vasa vasorum were associated with plaque regions in coronary arteries. In contrast, although the MCAs exhibited expanded intimas and established plaques, there were very few CD105 positive neovessels. Conclusion Our results show that CD105 is a useful marker of angiogenesis within adventitial and intimal vessels and suggest the existence of significant differences in the pathological development of atherosclerosis in separate vascular beds which may have important consequences when considering management and treatment of this disease.

  7. Establishment of atherosclerotic model and USPIO enhanced MRI techniques study in rabbits

    International Nuclear Information System (INIS)

    Objective: To explore the methods of establishment of atherosclerotic model and USPIO enhanced MRI techniques in rabbits. Methods: Thirty New Zealand male rabbits were divided randomly into two groups: 20 animals in the experiment group, 10 animals in the control group. Animal model of atherosclerosis was induced with aortic balloon endothelial injury and high-fat diet feeding. There was no intervention with the rabbits in control group. MRI examination included plan scan, USPIO enhanced black-blood sequences and white-blood sequence. The features of the plaques was analyzed in the experimental group and the effection on the image quality of different coils, sequences and parameters and a statistical study was also analyzed. Results: Animal model of atherosclerosis was successfully made in 12 rabbits and most plaques located in the abdomen aorta. There were 86 plaques within the scanning scope among which 67 plaques were positive to the Prussian blue staining. The image quality of knee joint coil was better than that of other coils. Although there was no difference in the detection of numbers of AS plaques between USPIO enhanced black-blood sequences and white-blood sequence (P > 0.05), blackblood sequences was superior to white-blood sequence in the demonstration of the components of plaque. Conclusion: The method of aortic balloon endothelial injury and high-fat diet feeding can easily establish the AS model in rabbits with a shorter period and it may be used for controlling the location of the plaques. USPIO enhanced MRI sequences has high sensitivity in the detection of the AS plauqes and can reveal the component of AS plaques. The optimization of MRI techniques is very important in the improvement of the image quality and the detection of the plaques. (authors)

  8. Error propagation in the characterization of atheromatic plaque types based on imaging.

    Science.gov (United States)

    Athanasiou, Lambros S; Rigas, George; Sakellarios, Antonis; Bourantas, Christos V; Stefanou, Kostas; Fotiou, Evangelos; Exarchos, Themis P; Siogkas, Panagiotis; Naka, Katerina K; Parodi, Oberdan; Vozzi, Federico; Teng, Zhongzhao; Young, Victoria E L; Gillard, Jonathan H; Prati, Francesco; Michalis, Lampros K; Fotiadis, Dimitrios I

    2015-10-01

    Imaging systems transmit and acquire signals and are subject to errors including: error sources, signal variations or possible calibration errors. These errors are included in all imaging systems for atherosclerosis and are propagated to methodologies implemented for the segmentation and characterization of atherosclerotic plaque. In this paper, we present a study for the propagation of imaging errors and image segmentation errors in plaque characterization methods applied to 2D vascular images. More specifically, the maximum error that can be propagated to the plaque characterization results is estimated, assuming worst-case scenarios. The proposed error propagation methodology is validated using methods applied to real datasets, obtained from intravascular imaging (IVUS) and optical coherence tomography (OCT) for coronary arteries, and magnetic resonance imaging (MRI) for carotid arteries. The plaque characterization methods have recently been presented in the literature and are able to detect the vessel borders, and characterize the atherosclerotic plaque types. Although, these methods have been extensively validated using as gold standard expert annotations, by applying the proposed error propagation methodology a more realistic validation is performed taking into account the effect of the border detection algorithms error and the image formation error into the final results. The Pearson's coefficient of the detected plaques has changed significantly when the method was applied to IVUS and OCT, while there was not any variation when the method was applied to MRI data. PMID:26165637

  9. Linking CD11b+ Dendritic Cells and Natural Killer T Cells to Plaque Inflammation in Atherosclerosis

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    Miche Rombouts

    2016-01-01

    Full Text Available Atherosclerosis remains the leading cause of death and disability in our Western society. To investigate whether the dynamics of leukocyte (subpopulations could be predictive for plaque inflammation during atherosclerosis, we analyzed innate and adaptive immune cell distributions in blood, plaques, and lymphoid tissue reservoirs in apolipoprotein E-deficient (ApoE−/− mice and in blood and plaques from patients undergoing endarterectomy. Firstly, there was predominance of the CD11b+ conventional dendritic cell (cDC subset in the plaque. Secondly, a strong inverse correlation was observed between CD11b+ cDC or natural killer T (NKT cells in blood and markers of inflammation in the plaque (including CD3, T-bet, CCR5, and CCR7. This indicates that circulating CD11b+ cDC and NKT cells show great potential to reflect the inflammatory status in the atherosclerotic plaque. Our results suggest that distinct changes in inflammatory cell dynamics may carry biomarker potential reflecting atherosclerotic lesion progression. This not only is crucial for a better understanding of the immunopathogenesis but also bares therapeutic potential, since immune cell-based therapies are emerging as a promising novel strategy in the battle against atherosclerosis and its associated comorbidities. The cDC-NKT cell interaction in atherosclerosis serves as a good candidate for future investigations.

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

    Directory of Open Access Journals (Sweden)

    Kengo Sato

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

  12. Plaque regression and plaque stabilisation in cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Tarun Dave

    2013-01-01

    Full Text Available Atherosclerosis is characterized by formation of plaques on the inner walls of arteries that threatens to become the leading cause of death worldwide via its sequelae of myocardial infarction and stroke. Endothelial dysfunction leads to cholesterol uptake and accumulation of infl ammatory markers within the plaque. The stability of a plaque eventually depends on the balance between vascular smooth muscle cells that stabilize it and the infl ammatory cells like macrophages and T lymphocytes that make it prone to rupture. The current approach to manage atherosclerosis focuses on the treatment of a ruptured plaque and efforts have been made to reduce the risk of plaque rupture by identifying vulnerable plaques and treating them before they precipitate into clinical events. New diagnostic approaches such as IVUS and CIMT ultrasound are now being preferred over traditional coronary angiography because of their better accuracy in measuring plaque volume rather than the level of stenosis caused. The present review highlights the literature available on two prevalent approaches to manage a vulnerable plaque, namely, plaque stabilization and plaque regression, and their validation through various treatment modalities in recent plaque management studies. Plaque stabilization focuses on stabilizing the content of plaque and strengthening the overlying endothelium, while plaque regression focuses on the overall reduction in plaque volume and to reverse the arterial endothelium to its normal functional state. Although earlier studies contemplated the practicality of plaque regression and focused greatly on stabilization of a vulnerable plaque, our review indicated that, aided by the use of superior diagnostics tools, more intensive lipid modifying therapies have resulted in actual plaque regression.

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

    Directory of Open Access Journals (Sweden)

    Martin Ungerer

    2012-06-01

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

  14. Treatment with sulphated galactan inhibits macrophage chemotaxis and reduces intraplaque macrophage content in atherosclerotic mice.

    Science.gov (United States)

    Gomes Quinderé, Ana Luíza; Barros Benevides, Norma Maria; Pelli, Graziano; Lenglet, Sébastien; Burger, Fabienne; Carbone, Federico; Fraga-Silva, Rodrigo A; Stergiopulos, Nikolaos; Pagano, Sabrina; Bertolotto, Maria; Dallegri, Franco; Vuilleumier, Nicolas; Mach, François; Montecucco, Fabrizio

    2015-08-01

    Experimental data from animal models and clinical studies support connections between the haemostasis and inflammation in atherogenesis. These interfaces among inflammation and thrombogenesis have been suggested as targets for pharmacological intervention to reduce disease progression. We hypothesize that the recently discovered antithrombotic drug Sulphated Galactan (SG) (isolated from the red marine alga Acanthophora muscoides) might reduce atherosclerotic plaque vulnerability and inflammatory gene expression in 10-week aged apolipoprotein E deficient (ApoE-/-) mice under high-cholesterol diet for additional 11weeks. Then, the underlying cellular mechanisms were investigated in vitro. SG (10mg/kg) or Vehicle was subcutaneously injected from week 6 until week 11 of the diet. Treatment with SG reduced intraplaque macrophage and Tissue Factor (TF) content as compared to Vehicle-treated animals. Intraplaque TF co-localized and positively correlated with macrophage rich-areas. No changes on atherosclerotic plaque size, and other intraplaque features of vulnerability (such as lipid, neutrophil, MMP-9 and collagen contents) were observed. Moreover, mRNA expression of MMPs, chemokines and genetic markers of Th1/2/reg/17 lymphocyte polarization within mouse aortic arches and spleens was not affected by SG treatment. In vitro, treatment with SG dose-dependently reduced macrophage chemotaxis without affecting TF production. Overall, the chronic SG treatment was well tolerated. In conclusion, our results indicate that SG treatment reduced intraplaque macrophage content (by impacting on cell recruitment) and, concomitantly, intraplaque TF content of potential macrophage origin in atherosclerotic mice. PMID:25869506

  15. Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling

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    Dmitry A. Chistiakov

    2015-01-01

    Full Text Available A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs and endothelial cells (ECs. These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role. The miR-221/222 cluster controls development and differentiation of ECs but inhibits their proangiogenic activation, proliferation, and migration. miR-221/222 are primarily implicated in maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular expression of miR-221/222 is upregulated in initial atherogenic stages causing inhibition of angiogenic recruitment of ECs and increasing endothelial dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and switching from the VSMC “contractile” phenotype to the “synthetic” phenotype associated with induction of proliferation and motility. In atherosclerotic vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation downregulates miR-221/222 expression in ECs that in turn could activate intralesion neoangiogenesis. In addition, both miRNAs could contribute to cardiovascular pathology through their effects on fat and glucose metabolism in nonvascular tissues such as adipose tissue, liver, and skeletal muscles.

  16. Study on Relationship Between Intima Medial Thickness and the Plaque in Stroke Patients on Carotid Artery Sonography

    International Nuclear Information System (INIS)

    The carotid intima-media thickness (IMT) is an early structural marker of the atherosclerotic process and is the only non-invasive test that is currently recommended by the American Heart Association for evaluation of the risk. However, use of this parameter has a limitation because it assumes uniform thickness throughout the blood vessel, whereas atherosclerosis is a focal phenomenon that is confined to intima. In fact, plaque can be found along the atherosclerotic blood vessels even though its value is unknown. The aim of this study is to analyze the carotid plaque and IMT in the stroke patients. We investigated the patients with ischemic stroke, who were admitted to the department of neurology at the Stroke Special Hospital from January to March 2008. After the carotid IMT and plaque were assessed by B-mode ultrasonography, IMT and carotid plaque to risk variables (age, sex) were analyzed. The distribution of CCA IMT was significantly different in terms of age (p = 0.004). Likewise, the distribution of carotid plaque was also significantly different in terms of age (p = 0.006). Carotid plaque was 69 and 92% in normal and abnormal CCA IMTs respectively. The results showed that the CCA IMT was closely associated with carotid plaque.

  17. Association between epicardial fat volume and coronary plaques diagnosed by multislice computed tomography

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    José A. Morán Quijada

    2016-01-01

    Full Text Available Introduction: Coronary atherosclerotic disease is a major cause of death in Cuba and elsewhere. The volume of epicardial fat is considered a new cardiovascular risk factor because of its association with coronary atherogenesis.Objective: To determine, by multislice computed tomography, the association between epicardial fat volume and the presence of coronary atherosclerotic plaques.Method: A descriptive study was conducted with a universe of 130 patients with chest pain suggestive of ischemic heart disease, of which 117 were selected by opinion sampling. These patients underwent a calcium score study, a coronary angiography and a measurement of the epicardial fat volume.Results: Male patients predominated (54.7% and those aged 60-69 years (32.5%. A high volume of epicardial fat was found in 51.3% of patients, affecting 52.8% of women; 78.9% of patients with a calcium score between 100 and 399 UH had a high volume of epicardial fat, just as 71.2% of those with plaques and 100% of those with 4 or 5 plaques; 41% of patients had various types of plaque, which were mainly located in the anterior descending artery (88.1%.Conclusions: The measurement of the volume of epicardial fat is a useful tool to estimate the presence of coronary disease. When it was high, it was associated with older age, female gender and the presence of a higher calcium score, more plaques, more injuries and a greater involvement of the anterior descending artery.

  18. Dental plaque identification at home

    Science.gov (United States)

    ... your teeth. Plaque is the major cause of tooth decay and gum disease ( gingivitis ). It is hard to ... the plaque is not removed, it can cause tooth decay or cause the gums to bleed easily (gingivitis) ...

  19. Cellular imaging of human atherosclerotic lesions by intravascular electric impedance spectroscopy.

    Directory of Open Access Journals (Sweden)

    Ines Streitner

    Full Text Available BACKGROUND: Newer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS is able to provide information about the cellular composition of biological tissue. The present study was performed to determine the influence of inflammatory processes in type Va (lipid core, thick fibrous cap and Vc (abundant fibrous connective tissue while lipid is minimal or even absent human atherosclerotic lesions on the electrical impedance of these lesions measured by EIS. METHODS AND RESULTS: EIS was performed on 1 aortic and 3 femoral human arteries at 25 spots with visually heavy plaque burden. Severely calcified lesions were excluded from analysis. A highly flexible micro-electrode mounted onto a balloon catheter was placed on marked regions to measure impedance values at 100 kHz. After paraffin embedding, visible marked cross sections (n = 21 were processed. Assessment of lesion types was performed by Movats staining. Immunostaining for CD31 (marker of neovascularisation, CD36 (scavenger cells and MMP-3 (matrix metalloproteinase-3 was performed. The amount of positive cells was assessed semi-quantitatively. 15 type Va lesions and 6 type Vc lesions were identified. Lesions containing abundant CD36-, CD31- and MMP-3-positive staining revealed significantly higher impedance values compared to lesions with marginal or without positive staining (CD36 + 455 ± 50 Ω vs. CD36- 346 ± 53 Ω, p = 0.001; CD31 + 436 ± 43 Ω vs. CD31- 340 ± 55 Ω, p = 0.001; MMP-3 + 400 ± 68 Ω vs. MMP-3- 323 ± 33 Ω, p = 0.03. CONCLUSIONS: Atherosclerotic lesions with abundant neovascularisation (CD31, many scavenger receptor class B expressing cells (CD36 or high amount of MMP-3 immunoreactivity reveal significantly higher impedance values compared to lesions with marginal or no detection of immunoreactivity. Findings suggest that inflammatory processes in vulnerable plaques affect the impedance of atherosclerotic

  20. Revascularisation of atherosclerotic mesenteric arteries

    DEFF Research Database (Denmark)

    Christensen, Max Greve; Lorentzen, Jørgen Ewald; Schroeder, T V

    1994-01-01

    25 patients, chronic ischaemia in 53 and prophylactic reconstruction in connection with aortic surgery in 12 patients. The superior mesenteric artery (SMA) was revascularised in 87 patients and the coeliac axis or common hepatic artery in six. Thus, only three patients had both territories......OBJECTIVES: Visceral artery surgery is well known to vascular surgeons, but most have limited personal experience. We report our experience with 90 patients treated for atherosclerotic lesions of the visceral arteries during a 25-year period 1968-1993. DESIGN: Retrospective study. SETTING...... revascularised. Thromboendarterectomy was performed in 15 patients, transposition of the SMA directly into the infrarenal aorta in 30 and bypass in 48 patients. CHIEF OUTCOME MEASURES: Cumulative symptom-free and survival rates. MAIN RESULTS: The overall perioperative (30 days) mortality rate was 13%, mainly...

  1. An assessment of the vulnerability of carotid plaques: a comparative study between intraplaque neovascularization and plaque echogenicity

    International Nuclear Information System (INIS)

    Carotid plaque echolucency as detected by Color Doppler ultrasonography (CDUS) has been used as a potential marker of plaque vulnerability. However, contrast-enhanced ultrasound (CEUS) has recently been shown to be a valuable method to evaluate the vulnerability and neovascularization within carotid atherosclerotic plaques. The aim of this study was to compare CEUS and CDUS in the assessment of plaque vulnerability using transcranial color Doppler (TCD) monitoring of microembolic signals (MES) as a reference technique. A total of 46 subjects with arterial stenosis (≥ 50%) underwent a carotid duplex ultrasound, TCD monitoring of MES and CEUS (SonoVue doses of 2.0 mL) within a span of 3 days. The agreement between the CEUS, CDUS, and MES findings was assessed with a chi-square test. A p-value less than 0.05 was considered statistically significant. Neovascularization was observed in 30 lesions (44.4%). The vascular risk factors for stroke were similar and there were no age or gender differences between the 2 groups. Using CEUS, MES were identified in 2 patients (12.5%) within class 1 (non-neovascularization) as opposed to 15 patients (50.0%) within class 2 (neovascularization) (p = 0.023). CDUS revealed no significant differences in the appearance of the MES between the 2 groups (hyperechoic and hypoechoic) (p = 0.237). This study provides preliminary evidence to suggest that intraplaque neovascularization detected by CEUS is associated with the presence of MESs, where as plaque echogenicity on traditional CDUS does not. These findings argue that CEUS may better identify high-risk plaques

  2. SELECTINS IN CORONARY ATHEROSCLEROTIC DISEASE:A REVIEW

    Institute of Scientific and Technical Information of China (English)

    李远方; 胡健

    2001-01-01

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

  3. Plaque size is decreased but M1 macrophage polarization and rupture related metalloproteinase expression are maintained after deleting T-bet in ApoE null mice

    OpenAIRE

    Tsaousi, Aikaterini; Hayes, Elaine; Di Gregoli, Karina; Bond, Andrew; Bevan, Laura; Thomas, Anita; Newby, Andrew

    2016-01-01

    Background: Thelper1 (Th1) lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1) macrophage activation or production of matrix degrading metalloproteinases (MMPs) and their tissue inhibitors, TIMPs. Methods & Results: We studied the effect of T-bet deletion in apolipoproteinE (ApoE) knockout mic...

  4. Plaque Size Is Decreased but M1 Macrophage Polarization and Rupture Related Metalloproteinase Expression Are Maintained after Deleting T-Bet in ApoE Null Mice

    OpenAIRE

    Tsaousi, Aikaterini; Hayes, Elaine M.; Di Gregoli, Karina; Bond, Andrew R.; Bevan, Laura; Thomas, Anita C.; Newby, Andrew C.

    2016-01-01

    Background Thelper1 (Th1) lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1) macrophage activation or production of matrix degrading metalloproteinases (MMPs) and their tissue inhibitors, TIMPs. Methods & Results We studied the effect of T-bet deletion in apolipoproteinE (ApoE) knockout mice fed ...

  5. Optimization of the K-edge imaging for vulnerable plaques using gold nanoparticles and energy-resolved photon counting detectors: a simulation study

    OpenAIRE

    Alivov, Yahya; Baturin, Pavlo; Le, Huy Q.; Ducote, Justin; Molloi, Sabee

    2013-01-01

    We investigated the effect of different imaging parameters such as dose, beam energy, energy resolution, and number of energy bins on image quality of K-edge spectral computed tomography (CT) of gold nanoparticles (GNP) accumulated in an atherosclerotic plaque. Maximum likelihood technique was employed to estimate the concentration of GNP, which served as a targeted intravenous contrast material intended to detect the degree of plaque's inflammation. The simulations studies used a single slic...

  6. [18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs

    OpenAIRE

    Tarkia, Miikka; Saraste, Antti; Stark, Christoffer; Vähäsilta, Tommi; Savunen, Timo; Strandberg, Marjatta; Saunavaara, Virva; Tolvanen, Tuula; Teuho, Jarmo; Teräs, Mika; Metsälä, Olli; Rinne, Petteri; Heinonen, Ilkka; Savisto, Nina; Pietilä, Mikko

    2015-01-01

    Objective Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model. Methods First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). Af...

  7. Selective ablation of atherosclerotic lesions with less thermal damage by controlling the pulse structure of a quantum cascade laser in the 5.7-µm wavelength range

    Science.gov (United States)

    Hashimura, Keisuke; Ishii, Katsunori; Awazu, Kunio

    2016-04-01

    Cholesteryl esters are the main components of atherosclerotic plaques, and they have an absorption peak at the wavelength of 5.75 µm. To realize less-invasive ablation of the atherosclerotic plaques using a quasi-continuous wave (quasi-CW) quantum cascade laser (QCL), the thermal effects on normal vessels must be reduced. In this study, we attempted to reduce the thermal effects by controlling the pulse structure. The irradiation effects on rabbit atherosclerotic aortas using macro pulse irradiation (irradiation of pulses at intervals) and conventional quasi-CW irradiation were compared. The macro pulse width and the macro pulse interval were determined based on the thermal relaxation time of atherosclerotic and normal aortas in the oscillation wavelength of the QCL. The ablation depth increased and the coagulation width decreased using macro pulse irradiation. Moreover, difference in ablation depth between the atherosclerotic and normal rabbit aortas using macro pulse irradiation was confirmed. Therefore, the QCL in the 5.7-µm wavelength range with controlling the pulse structure was effective for less-invasive laser angioplasty.

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

    Directory of Open Access Journals (Sweden)

    Tanasković Irena

    2010-01-01

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

  9. T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment.

    Science.gov (United States)

    Dong, Lei; Nordlohne, Johannes; Ge, Shuwang; Hertel, Barbara; Melk, Anette; Rong, Song; Haller, Hermann; von Vietinghoff, Sibylle

    2016-06-01

    Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe(-/-) (apolipoprotein E) CX3CR1(-/-) mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor-deficient (LDLr(-/-)) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1(-/-) bone marrow into LDLr(-/-) mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b(+)CD11c(+) myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1(-/-) splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFβ Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFβ alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFβ induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr(-/-) mice, CX3CR1(+/-) T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1(-/-) T cells did not. Transfer of CX3CR1(+/-) but not Il17a(-/-) T cells into LDLr(-/-)CX3CR1(-/-) mice increased aortic lesion size and aortic CD11b(+)CD11c(+) myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFβ and is instrumental in enhanced atherosclerosis in renal impairment. PMID:26449606

  10. The relationship between the angiographic findings and the clinical features of carotid artery plaque.

    Science.gov (United States)

    Kim, D I; Lee, S J; Lee, B B; Kim, Y I; Chung, C S; Seo, D W; Lee, K H; Ko, Y H; Kim, D K; Do, Y S; Byun, H S

    2000-01-01

    The purpose of this study was to investigate the histological characteristics of atheromatous carotid plaque, and to analyze the relationship between the angiographic findings and the clinical features. We retrospectively reviewed 55 cases of carotid endarterectomy for extracranial internal carotid artery stenosis, who were treated at our institute from January 1995 to December 1997. The histological examination included hematoxylin-eosin staining, Masson-trichrome staining, and immunostaining for antismooth muscle antibody and anti-CD68 antibody. The main compositions of the carotid plaque included synthetic type vascular smooth muscle cells and extracellular matrix. The histological findings showed ulceration in 49 (89.1%) cases, calcium deposits in 42 (76.4%) cases, and an inflammatory reaction in 44 (80.0%) cases. Neurological abnormalities were strongly associated with plaque ulceration (P = 0.045) and an inflammatory reaction (P = 0.013), whereas no correlation existed regarding calcium deposits (P = 0.173). The angiographic findings showed ulceration in 46 (83.6%) cases. Plaque ulceration in the angiography findings showed no statistically significant correlation with the histologic findings (P = 0.410) and preoperative neurologic abnormalities (P = 0.059). All of the atherosclerotic risk factors such as hypertension, smoking, diabetes mellitus, hyperlipidemia, and myocardial infarction had no statistically significant correlation with the histological features of the carotid plaque. In conclusion, the main compositions of carotid plaque were synthetic-type vascular smooth muscle cells and extracellular matrix. The histological ulceration and inflammatory reaction of the plaque showed a statistically significant correlation with the preoperative neurologic symptoms, whereas no correlation was seen in the calcium deposits. Angiographic ulceration showed no correlation with the histological findings or preoperative neurologic abnormalities. In addition, the

  11. Dental plaque - associated infections and antibacterial oral hygiene products.

    Science.gov (United States)

    Verran, J

    1991-02-01

    Synopsis Dental plaque accumulates on hard non-shedding surfaces such as teeth, dentures and orthodontic appliances. This accumulation is facilitated by the absence of adequate oral hygiene procedures. The term 'plaque' describes a mass of microorganisms embedded in an organic matrix of host and microbial origin. In addition to the aesthetic desirability of 'clean teeth, healthy gums and fresh breath' associated with the absence of plaque, obvious consequences of the presence of plaque include tooth decay (dental caries), gingivitis and periodontal (gum) disease and denture associated problems. Thus the prevention of plaque formation, the reduction of plaque accumulation and the effective removal of plaque are considerations of the cosmetic and health professions alike. There are many oral hygiene products available to the general public - toothpastes, mouthwashes, denture cleaners, and, more recently, chewing gums and novel mouthwashes. Several of these products have antimicrobial components. This paper reviews the microbiology of plaque and plaque associated problems, and surveys the type of products currently available for maintenance of good oral hygiene. Potential areas for future development are also explored. PMID:19291039

  12. Natural History of Intracranial Atherosclerotic Disease

    OpenAIRE

    YuehuaPu

    2014-01-01

    Intracranial atherosclerotic disease was very common among stroke patients of Asians, Blacks, and Hispanics ancestry. Furthermore, stroke patients with intracranial atherosclerosis (ICAS) have higher recurrence rate of cerebral ischemia and death than those without ICAS. However, the natural history of intracranial atherosclerotic disease is still in controversy. Most of the studies were retrospective and randomized controlled trial of drugs. This review summarized the prognosis of symptomati...

  13. Epigenetic Modulation in the treatment Atherosclerotic disease

    Directory of Open Access Journals (Sweden)

    Mikaela M Byrne

    2014-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Vincent Sarrazy

    2015-10-01

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

  15. High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined {sup 18}F-FDG PET/MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hyafil, Fabien [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Bichat University Hospital, Department of Nuclear Medicine, Paris (France); Schindler, Andreas; Obenhuber, Tilman; Saam, Tobias [Ludwig Maximilians University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Sepp, Dominik; Hoehn, Sabine; Poppert, Holger [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Bayer-Karpinska, Anna [Ludwig Maximilians University Hospital Munich, Institute for Stroke and Dementia Research, Munich (Germany); Boeckh-Behrens, Tobias [Technische Universitaet Muenchen, Department of Neuroradiology, Klinikum Rechts der Isar, Munich (Germany); Hacker, Marcus [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Nekolla, Stephan G. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Partner Site Munich Heart Alliance, German Centre for Cardiovascular Research (DZHK), Munich (Germany); Rominger, Axel [Ludwig Maximilians University Hospital Munich, Department of Nuclear Medicine, Munich (Germany); Dichgans, Martin [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Munich Cluster of Systems Neurology (SyNergy), Munich (Germany); Schwaiger, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

    2016-02-15

    The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and {sup 18}F-fluoro-deoxyglucose positron emission tomography ({sup 18}F-FDG PET) imaging. Carotid arteries were imaged 150 min after injection of {sup 18}F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections (n = 460) in both carotid arteries. {sup 18}F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections. The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher {sup 18}F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher {sup 18}F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques. Morphological and biological features of high-risk plaques can be detected with {sup 18}F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral

  16. High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined 18F-FDG PET/MR imaging

    International Nuclear Information System (INIS)

    The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG PET) imaging. Carotid arteries were imaged 150 min after injection of 18F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections (n = 460) in both carotid arteries. 18F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections. The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher 18F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher 18F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques. Morphological and biological features of high-risk plaques can be detected with 18F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral to the stroke, suggesting a causal role

  17. Rosiglitazone modulates pigeon atherosclerotic lipid accumulation and gene expression in vitro.

    Science.gov (United States)

    Anderson, J L; Keeley, M C; Smith, S C; Smith, E C; Taylor, R L

    2014-06-01

    Atherosclerosis is a major contributor to the overall United States mortality rate, primarily in the form of heart attacks and stroke. Unlike the human disease, which is believed to be multifactorial, pigeon atherosclerosis is due to a single gene autosomal recessive trait. The White Carneau (WC-As) strain develops atherosclerotic plaques without the presence of known environmental risk factors such as diet and classic predictors such as blood pressure or blood cholesterol levels. With similar parameters, the Show Racer (SR-Ar) is resistant to plaque development. Thiazolidinediones, including rosiglitazone, activate the peroxisome proliferator-activated receptor gamma (PPARγ) raising cellular sensitivity to insulin. The effect of rosiglitazone was evaluated in aortic smooth muscle cells (SMC) from these 2 pigeon breeds. Primary SMC cultures were prepared from WC-As and SR-Ar squabs. Cell monolayers, which achieved confluence in 7 d, were treated with 0 or 4 µM rosiglitazone for 24 h. Cellular lipid accumulation was evaluated by oil red O staining. Control WC-As cells had significantly higher vacuole scores and lipid content than did the SR-Ar control cells. Rosiglitazone treatment decreased WC-As lipid vacuoles significantly compared with the control cells. On the other hand, lipid vacuoles in the treated and untreated SR-Ar cells did not differ significantly. The effect of rosiglitazone on WC-As SMC gene expression was compared with control SMC using representational difference analysis. Significant transcript increases were found for caveolin and RNA binding motif in the control cells compared with the rosiglitazone-treated cells as well as cytochrome p450 family 17 subfamily A polypeptide 1 (CYP171A) in the rosiglitazone-treated cells compared with the control cells. Although rosiglitazone was selected for these experiments because of its role as a PPARγ agonist, it appears that the drug also tempers c-myc expression, as genes related to this second

  18. Development and psychometric validation of the REFlective evaLuation of psoriasis Efficacy of Treatment and Severity (REFLETS) questionnaire: a common measure of plaque-type psoriasis severity and treatment efficacy for patients and clinicians

    OpenAIRE

    Gilet, H; Roborel de Climens, A.; Arnould, B; Bachelez, H.; Bagot, M; Beaulieu, P; Joly, P.; Jullien, D; Le Maître, M; Ortonne, JP; Paul, C; Thibout, E.

    2014-01-01

    Background To date, there is no global consensus on the definition of the severity of psoriasis. The REFlective evaLuation of psoriasis Efficacy of Treatment and Severity (REFLETS) questionnaire has recently been developed to provide a better understanding of plaque-type psoriasis severity and treatment efficacy from both patient and clinician perspectives. Objective This study aimed to develop and psychometrically validate the new REFLETS questionnaire to evaluate patient and clinician perce...

  19. A computer-simulation study on the effects of MRI voxel dimensions on carotid plaque lipid-core and fibrous cap segmentation and stress modeling

    NARCIS (Netherlands)

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

    2015-01-01

    Background The benefits of a decreased slice thickness and/or in-plane voxel size in carotid MRI for atherosclerotic plaque component quantification accuracy and biomechanical peak cap stress analysis have not yet been investigated in detail because of practical limitations. Methods In order to p

  20. The high-risk plaque initiative

    DEFF Research Database (Denmark)

    Falk, Erling; Sillesen, Henrik; Muntendam, Pieter;

    2011-01-01

    The High-Risk Plaque (HRP) Initiative is a research and development effort to advance the understanding, recognition, and management of asymptomatic individuals at risk for a near-term atherothrombotic event such as myocardial infarction or stroke. Clinical studies using the newest technologies...... discovery studies. All individuals will be followed until 600 major atherothrombotic events have occurred in those undergoing imaging....

  1. Cobalt60 plaques in recurrent retinoblastoma

    International Nuclear Information System (INIS)

    Cobalt60 plaque irradiation is one treatment option for patients with recurrent retinoblastoma following conventional external beam irradiation (ERT). Tumorocidal doses can be delivered without excessive risk of normal tissue injury. In patients not considered candidates for xenon arc or cryotherapy, 60Co is an alternative to enucleation. Between 1968 and 1987, 85 patients were treated with 60Co plaques, 72 of whom had failed prior ERT. Age at diagnosis ranged from 1 week to 4 years. There are 37 males and 35 females. Seventy-one patients had bilateral disease and one had unilateral. Three patients had both eyes plaqued. Prior ERT ranged from 30 to 70 Gy (mean 4200 Gy). Time from initial therapy to failure ranged from 13 to 60 months. Cobalt plaques of 10 mm, 15 mm, or 10 x 15 mm were used depending on tumor size and location. Dose prescribed to the apex of the tumor ranged from 30 to 50 Gy (median 40 Gy) given over 3 to 8 days. Twelve patients had two plaque applications; three patients had three plaque applications. All patients were followed with routine ophthalmoscopic examinations. Follow-up ranged from 2 to 22 years (mean 8.7). Seven patients died of metastatic disease; 10 patients developed non-ocular second tumors. Thirty patients required enucleation. Twenty-two patients had clear tumor progression, two patients had radiation complications, and six patients had a combination of tumor growth and complications. Cobalt60 can salvage eyes in retinoblastoma patients failing ERT. Currently, the authors are using I125 in an attempt to spare normal ocular tissue and reduce subsequent complications

  2. Cobalt60 plaques in recurrent retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Fass, D.; McCormick, B.; Abramson, D.; Ellsworth, R. (Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, NY, NY (USA))

    1991-08-01

    Cobalt60 plaque irradiation is one treatment option for patients with recurrent retinoblastoma following conventional external beam irradiation (ERT). Tumorocidal doses can be delivered without excessive risk of normal tissue injury. In patients not considered candidates for xenon arc or cryotherapy, 60Co is an alternative to enucleation. Between 1968 and 1987, 85 patients were treated with 60Co plaques, 72 of whom had failed prior ERT. Age at diagnosis ranged from 1 week to 4 years. There are 37 males and 35 females. Seventy-one patients had bilateral disease and one had unilateral. Three patients had both eyes plaqued. Prior ERT ranged from 30 to 70 Gy (mean 4200 Gy). Time from initial therapy to failure ranged from 13 to 60 months. Cobalt plaques of 10 mm, 15 mm, or 10 {times} 15 mm were used depending on tumor size and location. Dose prescribed to the apex of the tumor ranged from 30 to 50 Gy (median 40 Gy) given over 3 to 8 days. Twelve patients had two plaque applications; three patients had three plaque applications. All patients were followed with routine ophthalmoscopic examinations. Follow-up ranged from 2 to 22 years (mean 8.7). Seven patients died of metastatic disease; 10 patients developed non-ocular second tumors. Thirty patients required enucleation. Twenty-two patients had clear tumor progression, two patients had radiation complications, and six patients had a combination of tumor growth and complications. Cobalt60 can salvage eyes in retinoblastoma patients failing ERT. Currently, the authors are using I125 in an attempt to spare normal ocular tissue and reduce subsequent complications.

  3. Detection of vulnerable plaques rather than the culprit lesions in patients with acute coronary syndrome using virtual histology intravascular ultrasound imaging

    Institute of Scientific and Technical Information of China (English)

    QIAN Ju-ying

    2009-01-01

    @@ Pathology and postmortem studies have reported that the most important mechanism of acute coronary syndrome (ACS) is the rupture of a vulnerable plaque and subsequent thrombus formation. Such events commonly arise from the non-flow limiting atherosclerotic lesions which are prone to rupture. Thin-cap fibroatheromas (TCFA) are the most common type of vulnerable plaque. As the widely used technique for the detection of coronary arterial diseases, coronary angiography has intrinsic limitations since it only portrays the contrast agent-filled contour of the lumen and provides little information on the vessel wall and even less the characteristics of the plaques.

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

    Science.gov (United States)

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

    2016-09-01

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

  5. Color doppler ultrasonography and multislice computer tomography angiography in carotid plaque detection and characterization

    Directory of Open Access Journals (Sweden)

    Vučaj-Ćirilović Viktorija

    2011-01-01

    Full Text Available Beckground/Aim. Cerebrovascular diseases are the third leading cause of mortality in the world, following malignant and cardiovascular diseases. Therefore, their timely and precise diagnostics is of great importance. The aim of this study was to compare duplex scan Color Doppler ultrasonography (CDU with multislice computed tomography angiography (MSCTA in detection of morphological and functional disorders at extracranial level of carotid arteries. Methods. The study included 75 patients with 150 carotid arteries examined in the period from January 2008 to April 2009. The patients were firstly examined by CDU, then MSCTA, followed by the surgery of extracranial segment of carotid arteries. In 10 patients, the obtained material was referred for histopathological (HP examination. We used both CDU and MSCT in the analysis of: plaque surface, plaque structure, degree of stenosis, and the presence of intraplaque hemorrhage. Results. The results obtained by CDU and MSCTA were first compared between themselves, and then to intraoperative findings. Retrospective analysis showed that MSCTA is more sensitive than CDU in assessment of plaque surface (for smooth plaques CDU 89% : MSCTA 97%; for plaques with irregular surface CDU 75% : MSCTA 87%; for ulcerations CDU 54% : MSCTA 87%. Regarding determination of plaque structure (mixed plaque CDU 66% : MSCTA 70%; correlation with HP findings CDU 94% : MSCTA 96% and localization (CDU 63% : MSCTA 65%, and in terms of sensitivity and specificity, both methods showed almost the same results. Also, there is no statistical difference between these two methods for the degree of stenosis (CDU 96% : MSCTA 98%. Conclusion. Atherosclerotic disease of extracranial part of carotid arteries primarily affects population of middle-aged and elderly, showing more associated risk factors. Sensitivity and specificity of CDU and MSCTA regarding plaque composition, the degree of stenosis and plaque localization are almost the same

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

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

    Science.gov (United States)

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

    2016-04-01

    Embedding of diagnostic and health care information requires secure encryption and watermarking. This research paper presents a comprehensive study for the behavior of some well established watermarking algorithms in frequency domain for the preservation of stroke-based diagnostic parameters. Two different sets of watermarking algorithms namely: two correlation-based (binary logo hiding) and two singular value decomposition (SVD)-based (gray logo hiding) watermarking algorithms are used for embedding ownership logo. The diagnostic parameters in atherosclerotic plaque ultrasound video are namely: (a) bulb identification and recognition which consists of identifying the bulb edge points in far and near carotid walls; (b) carotid bulb diameter; and (c) carotid lumen thickness all along the carotid artery. The tested data set consists of carotid atherosclerotic movies taken under IRB protocol from University of Indiana Hospital, USA-AtheroPoint™ (Roseville, CA, USA) joint pilot study. ROC (receiver operating characteristic) analysis was performed on the bulb detection process that showed an accuracy and sensitivity of 100 % each, respectively. The diagnostic preservation (DPsystem) for SVD-based approach was above 99 % with PSNR (Peak signal-to-noise ratio) above 41, ensuring the retention of diagnostic parameter devalorization as an effect of watermarking. Thus, the fully automated proposed system proved to be an efficient method for watermarking the atherosclerotic ultrasound video for stroke application. PMID:26860914

  9. The Frequency of Proximal ICA Plaques in Ischemic Symptom-Free Patients with Incidentally Detected Carotid Siphon Calcification

    Directory of Open Access Journals (Sweden)

    Sepideh Sefidbakht

    2009-01-01

    Full Text Available Introduction: Following the wide popularity of coronary artery Calcium scoring, efforts have been made to determine clinical significance of cavernous carotid calcification in relation to the risk of stroke. In this study we aimed to determine the correlation of carotid siphon calcification incidentally detected in head CT scans done for non-ischemic causes with presence and severity of bifurcation region plaques. "nMaterials and Methods: Overall 52 patients (29 male and 23 female, age range 67.8±10.76 with head CT scans done for non-ischemic causes were included. They included 40 patients with carotid siphon calcification detectable in the CT scan and 12 patients without cavernous carotid calcification included as control cases. All patients were evaluated for evidence of recent or previous ischemic events and atherosclerotic risk factors including blood pressure, BMI, history of smoking and cholesterol levels. All patients underwent color Doppler ultrasound of the cervical carotid artery by a single examiner blinded to the CT scan results. Calcification in the cavernous carotid region was semi-quantitatively graded according to Woodcock et al to no, mild, moderate and severe calcification. The degree of narrowing of the proximal ICA was graded to normal, narrowings <50%, 50-69%, ≥70% to near occlusion, near occlusion and total occlusion according to the Society of Radiologists in ultrasound consensus conference. Presence and degree of siphon calcification was correlated with presence and degree of bifurcation plaques using Mann-Whitney test. "nResults: Age range and atherosclerotic risk factors were not significantly different between case and control groups. Among 40 patients with siphon calcification of various degrees in the brain CT, 32 (75% were found to have at least mild narrowing plaques in color Doppler ultrasound. 7 out of 12 patients (58% with no calcification in CT were also found to have at least mildly narrowing plaques. The

  10. Carotid plaque characterization using CT and MRI scans for synergistic image analysis

    Science.gov (United States)

    Getzin, Matthew; Xu, Yiqin; Rao, Arhant; Madi, Saaussan; Bahadur, Ali; Lennartz, Michelle R.; Wang, Ge

    2014-09-01

    Noninvasive determination of plaque vulnerability has been a holy grail of medical imaging. Despite advances in tomographic technologies , there is currently no effective way to identify vulnerable atherosclerotic plaques with high sensitivity and specificity. Computed tomography (CT) and magnetic resonance imaging (MRI) are widely used, but neither provides sufficient information of plaque properties. Thus, we are motivated to combine CT and MRI imaging to determine if the composite information can better reflect the histological determination of plaque vulnerability. Two human endarterectomy specimens (1 symptomatic carotid and 1 stable femoral) were imaged using Scanco Medical Viva CT40 and Bruker Pharmascan 16cm 7T Horizontal MRI / MRS systems. μCT scans were done at 55 kVp and tube current of 70 mA. Samples underwent RARE-VTR and MSME pulse sequences to measure T1, T2 values, and proton density. The specimens were processed for histology and scored for vulnerability using the American Heart Association criteria. Single modality-based analyses were performed through segmentation of key imaging biomarkers (i.e. calcification and lumen), image registration, measurement of fibrous capsule, and multi-component T1 and T2 decay modeling. Feature differences were analyzed between the unstable and stable controls, symptomatic carotid and femoral plaque, respectively. By building on the techniques used in this study, synergistic CT+MRI analysis may provide a promising solution for plaque characterization in vivo.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-08-01

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

  12. Towards coronary plaque imaging using simultaneous PET-MR: a simulation study

    Science.gov (United States)

    Petibon, Y.; El Fakhri, G.; Nezafat, R.; Johnson, N.; Brady, T.; Ouyang, J.

    2014-03-01

    Coronary atherosclerotic plaque rupture is the main cause of myocardial infarction and the leading killer in the US. Inflammation is a known bio-marker of plaque vulnerability and can be assessed non-invasively using fluorodeoxyglucose-positron emission tomography imaging (FDG-PET). However, cardiac and respiratory motion of the heart makes PET detection of coronary plaque very challenging. Fat surrounding coronary arteries allows the use of MRI to track plaque motion during simultaneous PET-MR examination. In this study, we proposed and assessed the performance of a fat-MR based coronary motion correction technique for improved FDG-PET coronary plaque imaging in simultaneous PET-MR. The proposed methods were evaluated in a realistic four-dimensional PET-MR simulation study obtained by combining patient water-fat separated MRI and XCAT anthropomorphic phantom. Five small lesions were digitally inserted inside the patients coronary vessels to mimic coronary atherosclerotic plaques. The heart of the XCAT phantom was digitally replaced with the patient's heart. Motion-dependent activity distributions, attenuation maps, and fat-MR volumes of the heart, were generated using the XCAT cardiac and respiratory motion fields. A full Monte Carlo simulation using Siemens mMR's geometry was performed for each motion phase. Cardiac/respiratory motion fields were estimated using non-rigid registration of the transformed fat-MR volumes and incorporated directly into the system matrix of PET reconstruction along with motion-dependent attenuation maps. The proposed motion correction method was compared to conventional PET reconstruction techniques such as no motion correction, cardiac gating, and dual cardiac-respiratory gating. Compared to uncorrected reconstructions, fat-MR based motion compensation yielded an average improvement of plaque-to-background contrast of 29.6%, 43.7%, 57.2%, and 70.6% for true plaque-to-blood ratios of 10, 15, 20 and 25:1, respectively. Channelized

  13. Towards coronary plaque imaging using simultaneous PET-MR: a simulation study

    International Nuclear Information System (INIS)

    Coronary atherosclerotic plaque rupture is the main cause of myocardial infarction and the leading killer in the US. Inflammation is a known bio-marker of plaque vulnerability and can be assessed non-invasively using fluorodeoxyglucose-positron emission tomography imaging (FDG-PET). However, cardiac and respiratory motion of the heart makes PET detection of coronary plaque very challenging. Fat surrounding coronary arteries allows the use of MRI to track plaque motion during simultaneous PET-MR examination. In this study, we proposed and assessed the performance of a fat-MR based coronary motion correction technique for improved FDG-PET coronary plaque imaging in simultaneous PET-MR. The proposed methods were evaluated in a realistic four-dimensional PET-MR simulation study obtained by combining patient water–fat separated MRI and XCAT anthropomorphic phantom. Five small lesions were digitally inserted inside the patients coronary vessels to mimic coronary atherosclerotic plaques. The heart of the XCAT phantom was digitally replaced with the patient's heart. Motion-dependent activity distributions, attenuation maps, and fat-MR volumes of the heart, were generated using the XCAT cardiac and respiratory motion fields. A full Monte Carlo simulation using Siemens mMR's geometry was performed for each motion phase. Cardiac/respiratory motion fields were estimated using non-rigid registration of the transformed fat-MR volumes and incorporated directly into the system matrix of PET reconstruction along with motion-dependent attenuation maps. The proposed motion correction method was compared to conventional PET reconstruction techniques such as no motion correction, cardiac gating, and dual cardiac-respiratory gating. Compared to uncorrected reconstructions, fat-MR based motion compensation yielded an average improvement of plaque-to-background contrast of 29.6%, 43.7%, 57.2%, and 70.6% for true plaque-to-blood ratios of 10, 15, 20 and 25:1, respectively

  14. Photoabalation in dental hard substances and atheromatous plaques - The efficiency and selectivity criteria for surgery

    International Nuclear Information System (INIS)

    The basic principals of IR photoabalation are relatively easy to understand as long as water is the predominant absorber in the target tissue (e.g. brain tissue, cornea). Dental hard substances are typical target materials for the study of biological materials with low water content (30%) Its main constituent is hydroxyapatit (50%) with maximal absorption at 9.5 μm wavelength. The photoablation efficiency, the collateral thermal damage and the resultant formation of thermally induced surface cracks were investigated. Unlike the 2.95 μm of the Er:YAG, already in use, the 9.5 μm radiation minimizes the penetration depth; as a consequence, the volume of heated material per pulse is minimal too and thus thermal cracks - a potential source of caries are avoided. Furthermore at 9.5 μm, the ablation threshold requires a minimal fluence; this is an element of selectivity, limiting photoablation to dentin and enamel, while neighboring gingiva cannot be ablated accidentally. Removal of atherosclerotic plaques for recanalization of obliterated cardiac vessels (laser angioplasty) is a minimally invasive surgical procedure of highest socioeconomic relevance. The rather inhomogeneous composition of apatit and colesterol (both absorbing at 9.5 μm) make plaques a particularly complex target material; while the ablation efficiency has to be high, the related shock wave should be minimal. The open-quote selectivity close-quote criterion of the ablation process must avoid accidental perforation of the underlying vessel walls (composed of connective tissue with high water content), a deadly complication exclamation point Experimental results with FELIX will be demonstrated. Photoacoustic spectroscopy in a recently developed non contact mode has been proved to provide various informations (on line) about the IR-photoablation process

  15. Unique vascular protective properties of natural products: supplements or future main-line drugs with significant anti-atherosclerotic potential?

    Directory of Open Access Journals (Sweden)

    Slevin Mark

    2012-04-01

    Full Text Available Abstract Natural health products (NHP which include minerals, vitamins and herbal remedies are not generally considered by medical practitioners as conventional medicines and as such are not frequently prescribed by health centre’s as either main-line or supplemental treatments. In the field of cardiovascular medicine, studies have shown that typically, less than half of patients suffering from coronary syndromes chose to take any form of NHP supplement and these products are rarely recommended by their medical practitioner. Vascular/endothelial cell damage is a key instigator of coronary arterial plaque development which often culminates in thrombosis and myocardial infarction (MI. Current treatment for patients known to be at risk of primary or secondary (MI includes lipid lowering statins, anti-clotting agents (e.g. tissue plasminogen activator; tPA and drugs for stabilization of blood pressure such as beta-blockers. However, evidence has been building which suggests that components of at least several NHP (e.g. aged garlic extract (AGExt, resveratrol and green tea extracts (GTE may have significant vascular protective effects through reduction of oxidative stress, lowering of blood pressure, reduction in platelet aggregation, vasodilation and inhibition of abnormal angiogenesis. Therefore, in this review we will discuss in detail the potential of these substances (chosen on the basis of their potency and complimentarity as anti-atherosclerotic agents and the justification for their consideration as main-line additional supplements or prescriptions.

  16. Rheumatoid Arthritis Pharmacotherapies: Do They Have Anti-Atherosclerotic Activity?

    Science.gov (United States)

    Giles, Jon T

    2016-05-01

    Rheumatoid arthritis (RA) is associated with a heightened risk of cardiovascular disease (CVD) events, presumably related to a greater burden of atherosclerosis, as well as atherosclerotic plaques that tend to be inflamed and rupture prone. Many of the inflammatory pathways underlying the pathobiology of RA are also recognized contributors to atherosclerosis. Immunomodulation is the mainstay for RA therapy, and a variety of biologic and non-biologic pharmacotherapies are used either singly or in combination to control articular and systemic inflammation and prevent joint destruction. Almost all of these agents have theoretical potential to favorably affect atherogenesis and atherothrombosis, but mechanisms by which they exert effects have been incompletely studied, to date. However, whether clinical control of RA disease activity is associated with a reduction in CVD events regardless of agent used or whether the potency of anti-atherogenic effects varies between disease-modifying anti-rheumatic drugs (DMARDs) is an area of current interest in RA research. More broadly, RA immunotherapies are currently being tested in high-CVD-risk patients in proof-of-concept clinical trials that could alter the paradigm for CVD treatment and prevention in the general population. In this review, we will summarize the current evidence ascribing atheroprotective effects to RA pharmacotherapies. PMID:27032790

  17. Reducing dental plaque formation and caries development. A review of current methods and implications for novel pharmaceuticals.

    Science.gov (United States)

    Kalesinskas, Povilas; Kačergius, Tomas; Ambrozaitis, Arvydas; Pečiulienė, Vytautė; Ericson, Dan

    2014-01-01

    Dental caries is an oral disease, which has a high worldwide prevalence despite the availability of various prophylactic means, including the daily use of fluoride toothpastes, water fluoridation, dental sealants, oral health educational programs and various antiseptic mouth-rinses. One important reason for this is uncontrolled increase in consumption of foods containing considerable sucrose concentration, especially among children. Sucrose is easily metabolized by oral bacteria (mostly streptococci) to acids and, subsequently, causing tooth decay or dental caries. In the oral ecosystem, streptococci principally reside on tooth surfaces forming biofilm. Important structural and binding materials of biofilm are glucan polymers synthesized by several isoforms of glucosyltransferase enzyme present in certain species of oral bacteria, including mutans group streptococci - Streptococcus mutans and Streptococcus sobrinus, which preferably colonize humans. Thus, there is a constant need to develop the methods and chemotherapeutics for improving oral health care and decreasing teeth decay through the suppression of cariogenic biofilm formation in the oral cavity. The aim of this paper was to review literature related to the pathogenesis of dental caries as well as currently existing and experimental pharmaceutical substances used for prevention of this process. PMID:25209226

  18. Edible mushroom Agaricus sylvaticus can prevent the onset of atheroma plaques in hipercholesterolemic rabbits.

    Science.gov (United States)

    Percario, S; Odorizzi, V F; Souza, D R S; Pinhel, M A S; Gennari, J L; Gennari, M S; Godoy, M F

    2008-01-01

    Since the involvement of free radicals in the pathophysiology of atherosclerosis was proposed, antioxidant supplementation arose as a potential strategy for the management of this disease. Thus, we decided to investigate the potential benefit of a natural antioxidant--rich edible mushroom (Agaricus sylvaticus) on the prevention of atherosclerosis. New Zealand rabbits underwent atherosclerosis induction by feeding a cholesterol--enriched chow (Group A), while Group B simultaneously received edible mushroom A. sylvaticus water solution. Control group received standard rabbit chow only (Group C). At the end of 10 week treatment period serum samples were drawn for lipid profile, uric acid, thiobarbituric acid reactive substances (TBARS), and total antioxidant status (TAS). The area of aorta arteries taken by atheroma plaques was evaluated. Groups A and B presented higher cholesterol levels (p< 0.01) and reduced TAS (p<0.01), when compared to the Group C. However, TBARS and uric acid levels for Group B animals' were reduced, in comparison to Group A (p<0.05), and equals to group C. Moreover, animals from group A developed extensive atherosclerotic areas (47.0+/-14.0%), and that was prevented by the supplementation of A. sylvaticus (6.6+/-2.9%, p<0.01). Data suggested that A. sylvaticus can prevent the development of atherosclerosis in spite of hipercholesterolemia. PMID:19116085

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

    Directory of Open Access Journals (Sweden)

    Nicole Arend

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

  20. Effects of sugar-free chewing gum sweetened with xylitol or maltitol on the development of gingivitis and plaque: a randomized clinical trial

    NARCIS (Netherlands)

    R.S. Keukenmeester; D.E. Slot; N.A.M. Rosema; C. van Loveren; G.A. van der Weijden

    2014-01-01

    Objective The objective of this study was to test the effect of sugar-free chewing gum sweetened with xylitol or maltitol compared to the use of a gum base or no gum on gingivitis and plaque scores under both brushing and non-brushing circumstances. Methods The design of the study was a four-group,

  1. Cardiovascular magnetic resonance in carotid atherosclerotic disease

    Directory of Open Access Journals (Sweden)

    Chen Huijun

    2009-12-01

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

  2. Proteomic Profile of Unstable Atheroma Plaque: Increased Neutrophil Defensin 1, Clusterin, and Apolipoprotein E Levels in Carotid Secretome.

    Science.gov (United States)

    Aragonès, Gemma; Auguet, Teresa; Guiu-Jurado, Esther; Berlanga, Alba; Curriu, Marta; Martinez, Salomé; Alibalic, Ajla; Aguilar, Carmen; Hernández, Esteban; Camara, María-Luisa; Canela, Núria; Herrero, Pol; Ruyra, Xavier; Martín-Paredero, Vicente; Richart, Cristóbal

    2016-03-01

    Because of the clinical significance of carotid atherosclerosis, the search for novel biomarkers has become a priority. The aim of the present study was to compare the protein secretion profile of the carotid atherosclerotic plaque (CAP, n = 12) and nonatherosclerotic mammary artery (MA, n = 10) secretomes. We used a nontargeted proteomic approach that incorporated tandem immunoaffinity depletion, iTRAQ labeling, and nanoflow liquid chromatography coupled to high-resolution mass spectrometry. In total, 162 proteins were quantified, of which 25 showed statistically significant differences in secretome levels between carotid atherosclerotic plaque and nondiseased mammary artery. We found increased levels of neutrophil defensin 1, apolipoprotein E, clusterin, and zinc-alpha-2-glycoprotein in CAP secretomes. Results were validated by ELISA assays. Also, differentially secreted proteins are involved in pathways such as focal adhesion and leukocyte transendothelial migration. In conclusion, this study provides a subset of identified proteins that are differently expressed in secretomes of clinical significance. PMID:26795031

  3. 99mTc-labelled anti-CD11b SPECT/CT imaging allows detection of plaque destabilization tightly linked to inflammation.

    Science.gov (United States)

    Liu, Guobing; Hu, Yan; Xiao, Jie; Li, Xiao; Li, Yanli; Tan, Hui; Zhao, Yanzhao; Cheng, Dengfeng; Shi, Hongcheng

    2016-01-01

    It remains challenging to predict the risk of rupture for a specific atherosclerotic plaque timely, a thrombotic trigger tightly linked to inflammation. CD11b, is a biomarker abundant on inflammatory cells, not restricted to monocytes/macrophages. In this study, we fabricated a probe named as (99m)Tc-MAG3-anti-CD11b for detecting inflamed atherosclerotic plaques with single photon emission computed tomography/computed tomography (SPECT/CT). The ApoE-knockout (ApoE(-/-)) mice were selected to establish animal models, with C57BL/6J mice used for control. A higher CD11b(+)-cell recruitment with higher CD11b expression and more serious whole-body inflammatory status were identified in ApoE(-/-) mice. The probe showed high in vitro affinity and specificity to the Raw-264.7 macrophages, as well as inflammatory cells infiltrated in atherosclerotic plaques, either in ex vivo fluorescent imaging or in in vivo micro-SPECT/CT imaging, which were confirmed by ex vivo planar gamma imaging, Oil-Red-O staining and CD11b-immunohistochemistry staining. A significant positive relationship was identified between the radioactivity intensity on SPECT/CT images and the CD11b expression in plaques. In summary, this study demonstrates the feasibility of anti-CD11b antibody mediated noninvasive SPECT/CT imaging of inflammatory leukocytes in murine atherosclerotic plaques. This imaging strategy can identify inflammation-rich plaques at risk for rupture and evaluate the effectiveness of inflammation-targeted therapies in atheroma. PMID:26877097

  4. Three-dimensional reconstruction and analysis of structure characteristics on senile plaques of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    YE Wei; LIU Jianwu; ZHOU Jiangning; HU Xiangyou; TANG Xiaowei

    2005-01-01

    Alzheimer's disease is a progressive neuro- degenerative disorder characterized by the presence of senile plaques primarily composed of amyloid ( in brain. Abnormal secretion and aggregation of amyloid ( are the key events in pathogenesis of Alzheimer's disease. Reduction of amyloid ( production and inhibition of amyloid ( aggregation to form senile plaques are hopeful strategies for the treatment and prevention of Alzheimer's disease. In the present study, the silver and immunohistochemical staining methods were applied to discover senile plaques in the hippocampus of Alzheimer's disease patients, and then images were processed and three-dimensionally reconstructed by Matlab and AVS software. The structure characteristics of senile plaques were measured through correlation function calculation and fractal dimension by a computer-aided method. Diffuse plaque had no amyloid center, but classic plaque presented compact central core structure; two types of plaques were both of porous structure, but the sizes of their pores were significantly different. Furthermore, there was difference in fractal dimension value between the diffuse plaque and classic plaque in the two staining methods. The comparison of structure characteristics between two types of plaques indicated that they developed independently. Establishment of the methods for reconstructing the three-dimen- sional structure of senile plaque and analyzing their structure characteristics is helpful for further study on the aggregation mechanism of senile plaque.

  5. Diode-light transillumination for ophthalmic plaque localization around juxtapapillary choroidal melanomas

    International Nuclear Information System (INIS)

    Purpose: An evaluation of plaque-mounted diode-light transillumination (DLT) for localization of episcleral plaques beneath juxtapapillary tumors. Methods and materials: Two patients scheduled for radiotherapy for juxtapapillary melanomas were offered DLT as an additional method of ophthalmic plaque localization. Plaques were constructed by affixing 4 non-heat producing, light-emitting diodes with their apertures flush with the episcleral outer surface of the plaque's rim. Bio-implantable epoxy was used to encapsulate the electronic components. Then the plaques were loaded with 103Pd seeds. After the eye-plaques were sewn to the episclera covering the base of the intraocular tumors, the diode-lights were illuminated, viewed and recorded. Photodocumentation of the relative position of the 4 lights around tumor's base was obtained in both cases. Results: Digital images of plaque-mounted diode retro-transillumination were obtained. No evidence of diode-light toxicity was noted. Both tumors were found to be covered by the ophthalmic plaques. Conclusion: Juxtapapillary tumors are often difficult or impossible to visualize with standard transillumination techniques and have been associated with poor local control rates. We have developed plaque-mounted DLT in an effort to improve ophthalmic plaque localization. Retrobulbar transillumination was viewed by indirect ophthalmoscopy and recorded with video-imaging. This technique provides unique photographic documentation of episcleral plaque localization beneath juxtapapillary tumors

  6. The association of lesion eccentricity with plaque morphology and components in the superficial femoral artery: a high-spatial-resolution, multi-contrast weighted CMR study

    Directory of Open Access Journals (Sweden)

    Zhao Xihai

    2010-07-01

    Full Text Available Abstract Background Atherosclerotic plaque morphology and components are predictors of subsequent cardiovascular events. However, associations of plaque eccentricity with plaque morphology and plaque composition are unclear. This study investigated associations of plaque eccentricity with plaque components and morphology in the proximal superficial femoral artery using cardiovascular magnetic resonance (CMR. Methods Twenty-eight subjects with an ankle-brachial index less than 1.00 were examined with 1.5T high-spatial-resolution, multi-contrast weighted CMR. One hundred and eighty diseased locations of the proximal superficial femoral artery (about 40 mm were analyzed. The eccentric lesion was defined as [(Maximum wall thickness- Minimum wall thickness/Maximum wall thickness] ≥ 0.5. The arterial morphology and plaque components were measured using semi-automatic image analysis software. Results One hundred and fifteen locations were identified as eccentric lesions and sixty-five as concentric lesions. The eccentric lesions had larger wall but similar lumen areas, larger mean and maximum wall thicknesses, and more calcification and lipid rich necrotic core, compared to concentric lesions. For lesions with the same lumen area, the degree of eccentricity was associated with an increased wall area. Eccentricity (dichotomous as eccentric or concentric was independently correlated with the prevalence of calcification (odds ratio 3.78, 95% CI 1.47-9.70 after adjustment for atherosclerotic risk factors and wall area. Conclusions Plaque eccentricity is associated with preserved lumen size and advanced plaque features such as larger plaque burden, more lipid content, and increased calcification in the superficial femoral artery.

  7. Association between carotid plaque composition assessed by multidetector computed tomography and cerebral embolism after carotid stenting

    Energy Technology Data Exchange (ETDEWEB)

    Uchiyama, Naoyuki [Kanazawa University, Department of Neurosurgery and Radiology, Graduate School of Medical Science, Kanazawa (Japan); Kanazawa University, Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa, Ishikawa (Japan); Misaki, Kouichi; Mohri, Masanao; Watanabe, Takuya; Hirota, Yuichi; Nakada, Mitsutoshi; Hayashi, Yutaka; Ueda, Fumiaki; Hamada, Jun-ichiro [Kanazawa University, Department of Neurosurgery and Radiology, Graduate School of Medical Science, Kanazawa (Japan)

    2012-05-15

    We aimed to assess the relationship between atherosclerotic carotid plaque composition analyzed using multidetector computed tomography (MDCT) and the appearance of new ischemic lesions detected by diffusion-weighted images (DWI) after carotid artery stenting (CAS). We quantitatively and qualitatively analyzed plaque characteristics in carotid arteries using MDCT before CAS in 19 patients. Carotid plaques were expediently subdivided into four components with Hounsfield unit (HU) values of <0, 0-60, 60-130, and >600. The incidence of distal embolism was evaluated with DWI. Pearson's correlation analyses were used to assess the association between plaque composition and the incidence of cerebral embolization. Fifteen patients (79%) demonstrated new DWI lesions after CAS. High-signal DWIs were noted as follows: one in six patients, 2{proportional_to}5 in five patients, 6{proportional_to}10 in two patients, and >10 in two patients. The mean volumes of the plaque components for HU < 0, 0-60, 60-130, and >600 were 5.4, 200, 260, and 59 mm{sup 3}, respectively. There was a strong correlation between the number of high-signal DWI lesions in the ipsilateral side and the plaque volume of HU < 0 (r = 0.927; P < 0.0001). There was a moderate correlation between the number of high-signal DWI lesions and the plaque volume of HU 0-60 (r = 0.568; P = 0.0099) and the sum total of HU < 0 and HU 0-60 (r = 0.609; P = 0.0047). Quantitative and qualitative tissue characterization of carotid plaques using MDCT might be a useful predictor for silent ischemic lesions after CAS. (orig.)

  8. Argonne National Laboratory research offers clues to Alzheimer's plaques

    CERN Multimedia

    2003-01-01

    Researchers from Argonne National Laboratory and the University of Chicago have developed methods to directly observe the structure and growth of microscopic filaments that form the characteristic plaques found in the brains of those with Alzheimer's Disease (1 page).

  9. Vascular morphologic and functional effect of endogenous androgens in an experimental atherosclerotic rabbits model

    International Nuclear Information System (INIS)

    Previous clinical and experimental studies suggest that androgens could have adverse, neutral or beneficial effect on atherosclerosis and its clinical manifestations. Methods: an experimental, randomized controlled study in 40 New Zeland white male rabbits was realized. 20 rabbits underwent orchidectomy and 20 were fed with an atherogenic diet for 20 weeks. These were distributed in four groups: 1. non-castrated under normal diet, 2. Castrated under normal diet, 3. non-castrated under atherogenic diet, and 4. Castrated under atherogenic diet. Total cholesterol and free testosterone were measured. After euthanasia, arterial relaxation independent of endothelium was quantified in aorta, as well as the one depending on endothelium, in vitro, and histomorphometric analysis of thoracic aorta were made in order to quantify the atherosclerotic plaque formation. Results: animals that had a normal diet (n=20) had total cholesterol of 51.1 ± 8.5 mg/dl and those with atherogenic diet of 429.2 ± 262.0 mg/dl (p< 0.001). Testosterone levels in the non- castrated group were 2.1 ± 0.3 ng/ml and in the castrated were 0.8 ± 0.4 ng/ml (p= 0.024). In non-castrated rabbits the effect of hypercholesterolemia (366 ± 226.1 mg/dl) inducing atherosclerotic plaque and functional vascular alteration was mild. On the other hand, atherogenic diet in castrated rabbits induced an increment in total cholesterol from 387.6 ± 292.7 mg/dl (p <0.001) and severe morphological changes such as plaque area 2.6 ± 2.3mm (p <0.001), vessel plaque/area 0.25 ± 0.1 (p <0.001) and area index of plaque/area of the media 0.4 ± 0.3 (p <0.001). Endothelium independent relaxation percentage was 85.5 ± 14.3% (p = NS) and endothelium dependent relaxation was 38.5 ± 201% (p = 0.03). Conclusion: This study realized in rabbits demonstrates that endogenous testosterone might have a preventive effect on atherosclerosis and favor endothelium dependent vascular relaxation in the presence of severe

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

    DEFF Research Database (Denmark)

    van Engelen, Arna; Niessen, Wiro J.; Klein, Stefan;

    2014-01-01

    , fibrous and lipid-rich necrotic tissue, using linear discriminant (LDC) and support vector machine (SVM) classification. In addition, the combination of MRI and CTA data was compared to using only one imaging modality. Best results were obtained by LDC and outlier rejection: the volume error per vessel...

  11. The effect of aging on atherosclerotic plaque inflammation and molecular calcification: A PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Simonsen, Jane Angel;

    cardiovascular risk factors were prospectively assessed by 18F-FDG (inflammation) and sodium 18F-fluoride (18F-NaF) (molecular calcification) PET CT imaging. Global aortic uptake of 18F-FDG and 18F-NaF was determined semi-quantitatively by calculating the average blood pool corrected standardized uptake value (cSUV......) [Mean SUVAORTA - Mean SUVBLOOD POOL]. Furthermore, the average maximum 18F-NaF cSUV was determined in the coronary arteries. Calculating regression and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18F-FDG avidity. A second order...

  12. Actin Is a Target of T-Cell Reactivity in Patients with Advanced Carotid Atherosclerotic Plaques

    OpenAIRE

    Elisabetta Profumo; Brigitta Buttari; Linda Petrone; Giada Lacroce; Maria Chiara Tesori; Raffaele Capoano; Bruno Salvati; Rachele Riganò

    2013-01-01

    Atherosclerosis is a chronic inflammatory disease of the arterial wall associated with autoimmune reactions. In a previous study, we observed the presence of actin-specific antibodies in sera from patients with carotid atherosclerosis. To extend our previous results we evaluated the possible role of actin as antigenic target of cell-mediated immune reactions in carotid atherosclerosis. Peripheral blood mononuclear cells (PBMC) from 17 patients and 16 healthy subjects were tested by cell proli...

  13. Actin Is a Target of T-Cell Reactivity in Patients with Advanced Carotid Atherosclerotic Plaques

    Directory of Open Access Journals (Sweden)

    Elisabetta Profumo

    2013-01-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease of the arterial wall associated with autoimmune reactions. In a previous study, we observed the presence of actin-specific antibodies in sera from patients with carotid atherosclerosis. To extend our previous results we evaluated the possible role of actin as antigenic target of cell-mediated immune reactions in carotid atherosclerosis. Peripheral blood mononuclear cells (PBMC from 17 patients and 16 healthy subjects were tested by cell proliferation assay and by ELISA for cytokine production. Actin induced a proliferative response in 47% of patients’ PBMC samples, with SI ranging from 2.6 to 21.1, and in none of the healthy subjects’ samples (patients versus healthy subjects, P=0.02. The presence of diabetes in patients was significantly associated with proliferative response to actin (P=0.04. IFN-γ and TNF-α concentrations were higher in PBMC from patients than in those from healthy subjects and in PBMC proliferating to actin than in nonproliferating ones. Our data demonstrate for the first time a role of actin as a target autoantigen of cellular immune reactions in patients with carotid atherosclerosis. The preferential proinflammatory Th1 activation suggests that actin could contribute to endothelial dysfunction, tissue damage, and systemic inflammation in carotid atherosclerosis.

  14. Atherosclerotic plaque and hydroxyapatite nanostructures studied by high-frequency EPR

    OpenAIRE

    Gafurov, M. R.; YAVKIN B.V.; BIKTAGIROV T.B.; MAMIN G.V.; Orlinskii, S.B.; Izotov, V. V.; Salakhov M.Kh.; KLIMASHINA E.S.; PUTLAYEV V.I.; ABDUL’YANOV V.A.; IGNATJEV I.M.; KHAIRULLIN R.N.; ZAMOCHKIN A.V.; CHELYSHEV YU.A.

    2013-01-01

    A series of nanosized (20 nm and larger) samples of hydroxyapatite powders synthesized by wet preparation method and doped with Mn 2+ and Pb 2+ ions were studied by 94 GHz pulsed electron paramagnetic resonance (EPR). The results are compared with those obtained in the samples of aorta walls from male patients with atherosclerosis as well as in bulk hydroxyapatite materials. It is shown that in contrast to bulk materials Pb ions at least partially replace the Ca(1) site in the hydroxyapatite ...

  15. Direct detection and quantification of transition metal ions in human atherosclerotic plaques

    DEFF Research Database (Denmark)

    Stadler, Nadina; Lindner, Robyn A; Davies, Michael Jonathan

    2004-01-01

    copper in ex vivo healthy human arteries and carotid lesions. The EPR spectra detected are characteristic of nonheme Fe(III) complexes. Statistically elevated levels of iron were detected in the intima of lesions compared with healthy controls (0.370 versus 0.022 nmol/mg tissue for EPR, 0.525 versus 0......OBJECTIVE: The involvement of transition metals in atherosclerosis is controversial. Some epidemiological studies have reported a relationship between iron (Fe) and cardiovascular disease, whereas others have not. Experimental studies have reported elevated levels of iron and copper (Cu) in.......168 nmol/mg tissue by ICPMS, P<0.05 in each cases). Elevated levels of copper were also detected (7.51 versus 2.01 pmol/mg tissue, lesion versus healthy control, respectively, P<0.05). Iron levels did not correlate with the gender or age of the donor, or tissue protein or calcium levels, but cholesterol...

  16. Evaluation of atherosclerotic lesions using dextran- and mannan–dextran-coated USPIO: MRI analysis and pathological findings

    Directory of Open Access Journals (Sweden)

    Mukaisho K

    2012-05-01

    Full Text Available Keiko Tsuchiya1, Norihisa Nitta1, Akinaga Sonoda1, Ayumi Nitta-Seko1, Shinichi Ohta1, Masashi Takahashi1, Kiyoshi Murata1, Kenichi Mukaisho2, Masashi Shiomi3, Yasuhiko Tabata4, Satoshi Nohara51Department of Radiology, 2Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, 3Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Hyogo, 4Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 5Nagoya Research Laboratory, Meito Sangyo, Kiyosu, Aichi, JapanAbstract: Magnetic resonance imaging (MRI can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic iron oxides (USPIO. Positing that improved USPIO with a higher affinity for atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of dextran- and mannan–dextran-coated USPIO (D-USPIO and DM-USPIO, respectively by the atherosclerotic walls of rabbits. We intravenously injected atherosclerotic rabbits with DM-USPIO (n = 5 or D-USPIO (n = 5. Two rabbits were the controls. The doses delivered were 0.08 (dose 1 (n = 1, 0.4 (dose 2 (n = 1, or 0.8 (dose 3 (n = 3 mmol iron/Kg. The dose 3 rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA before and 5 days after USPIO administration. Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR of the aortic wall in the same region of interest (ROI was calculated in both in vivo and in vitro studies. Histological assessment through measurement of iron-positive regions in Prussian blue-stained specimens showed that iron-positive regions were significantly larger in rabbits injected with DM- rather than D-USPIO (P < 0.05 for all doses. In vivo MRA showed that the SNR-reducing effect of DM- was greater than that of D-USPIO (P < 0.05. With in vitro MRI scans, SNR was significantly

  17. Disappearance of La Caille Plaque

    Science.gov (United States)

    2010-04-01

    A bronze plaque erected to the memory of N.-L. de La Caille near the site of his observatory in Central Cape Town, has been stolen by metal thieves. It was designed by the famous architect Sir Herbert Baker.

  18. Localization of oxidized low-density lipoprotein and its relation to plaque morphology in human coronary artery.

    Directory of Open Access Journals (Sweden)

    Yasumi Uchida

    Full Text Available OBJECTIVES: Oxidized low-density lipoprotein (oxLDL plays a key role in the formation of atherosclerotic plaques. However, its localization in human coronary arterial wall is not well understood. The present study was performed to visualize deposition sites and patterns of native oxLDL and their relation to plaque morphology in human coronary artery. METHODS: Evans blue dye (EB elicits a violet fluorescence by excitation at 345-nm and emission at 420-nm, and a reddish-brown fluorescence by excitation at 470-nm and emission at 515-nm characteristic of oxLDL only. Therefore, native oxLDL in excised human coronary artery were investigated by color fluorescent microscopy (CFM using EB as a biomarker. RESULTS: (1 By luminal surface scan with CFM, the % incidence of oxLDL in 38 normal segments, 41 white plaques and 32 yellow plaques that were classified by conventional angioscopy, was respectively 26, 44 and 94, indicating significantly (p<0.05 higher incidence in the latter than the former two groups. Distribution pattern was classified as patchy, diffuse and web-like. Web-like pattern was observed only in yellow plaques with necrotic core. (2 By transected surface scan, oxLDL deposited within superficial layer in normal segments and diffusely within both superficial and deep layers in white and yellow plaques. In yellow plaques with necrotic core, oxLDL deposited not only in the marginal zone of the necrotic core but also in the fibrous cap. CONCLUSION: Taken into consideration of the well-known process of coronary plaque growth, the results suggest that oxLDL begins to deposit in human coronary artery wall before plaque formation and increasingly deposits with plaque growth, exhibiting different deposition sites and patterns depending on morphological changes.

  19. Detection of Atherosclerotic Lesion with 99mTc-LDL Scintigraphy

    International Nuclear Information System (INIS)

    Diagnostic approaches such as angiography, ultrasound, computed tomography and nuclear magnetic resonance have limitation for contributing to the early clinical diagnosis of atherosclerosis. Recently, 99mTc-labelled low density lipoprotein was developed to detect early atherosclerotic lesion by external imaging with gamma camera. To determine whether 99mTc- LDL scintigraphy can visualize the active atherosclerotic lesion, rabbits were injected with 99mTc-LDL, 3 months after feeding dietary fat (lanolin) and we obtained following results. 1) Labelling efficiency of 99mTc-LDL was 79 ∼ 88%. 2) Biodistribution study of normal rabbits with 99mTc-LDL revealed the high activities in spleen, adrenal gland, liver, kidney which are major organs of high metabolic rate of LDL. 3) Three months after feeding lanolin, serum cholesterol was markedly increased from 74 ± 17 mg/dl to 979 ± 153 mg/dl and histologic study of aorta after sacrificing the rabbit demonstrated marked atherosclerotic changes. 4) Atherosclerotic lesion of abdominal aorta which was confirmed with histologic study could be demonstrated in 99mTc-LDL scintigraphy after feeding lanolin for 3 months. In conclusion, the results of this preliminary investigation suggest that it may be possible to image active atheromatous lesion with 99mTc-LDL. It is anticipated that this promising agent may allow the in vive monitoring of preclinical atherosclerotic lesions and may be useful to evaluate the metabolic path way of LDL in humans.

  20. Detection of Atherosclerotic Lesion with {sup 99m}Tc-LDL Scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Deog Yoon; Koh, Eun Mi; Woo, Jeong Taek; Kim, Sung Woon; Yang, In Myung; Kim, Jin Woo; Kim, Young Seol; Kim, Kwang Won; Choi, Young Kil [Kyung Hee University School of Medicine, Seoul (Korea, Republic of)

    1992-07-15

    Diagnostic approaches such as angiography, ultrasound, computed tomography and nuclear magnetic resonance have limitation for contributing to the early clinical diagnosis of atherosclerosis. Recently, {sup 99m}Tc-labelled low density lipoprotein was developed to detect early atherosclerotic lesion by external imaging with gamma camera. To determine whether {sup 99m}Tc- LDL scintigraphy can visualize the active atherosclerotic lesion, rabbits were injected with {sup 99m}Tc-LDL, 3 months after feeding dietary fat (lanolin) and we obtained following results. 1) Labelling efficiency of {sup 99m}Tc-LDL was 79 approx 88%. 2) Biodistribution study of normal rabbits with {sup 99m}Tc-LDL revealed the high activities in spleen, adrenal gland, liver, kidney which are major organs of high metabolic rate of LDL. 3) Three months after feeding lanolin, serum cholesterol was markedly increased from 74 +- 17 mg/dl to 979 +- 153 mg/dl and histologic study of aorta after sacrificing the rabbit demonstrated marked atherosclerotic changes. 4) Atherosclerotic lesion of abdominal aorta which was confirmed with histologic study could be demonstrated in {sup 99m}Tc-LDL scintigraphy after feeding lanolin for 3 months. In conclusion, the results of this preliminary investigation suggest that it may be possible to image active atheromatous lesion with {sup 99m}Tc-LDL. It is anticipated that this promising agent may allow the in vive monitoring of preclinical atherosclerotic lesions and may be useful to evaluate the metabolic path way of LDL in humans.

  1. Periodontal pathogens in atheromatous plaque

    Directory of Open Access Journals (Sweden)

    Saroj K. Rath

    2014-01-01

    Full Text Available Background: There has been increasing attention paid in recent years to the possibility that oral bacterial infection, particularly periodontal disease may influence the initiation and or progression of systemic diseases. These studies confirm the observation that heart disease is the most commonly found systemic condition in patients with periodontal disease. Moreover, the literature has also highlighted substantial evidence indicating the presence of Gram-negative periodontal pathogens in atheromatous plaques. Aim: This study intends to investigate the possible association between periodontal health and coronary artery disease by evaluating periodontal status, association between the periodontal plaque and coronary atheromatous plaques for presence of micro-organisms such as, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia. Materials and methods: A case-control study was designed with seven patients who had undergone coronary endarterectomy for cardiovascular disease and 28 controls. The periodontal examination for cases was performed 1 day before vascular surgery and the controls were clinically examined. The atheromatous plaque sample collected during endarterectomy and the intraoral plaque samples were subjected to polymerase chain reaction for identification of A. actinomycetemcomitans, P. gingivalis, P. intermedia and T. forsythia. Results: The presence of periodontal bacteria DNA in coronary atheromatous plaques and sub-gingival plaque samples of the same patients was confirmed by this study. CONCLUSION A correlation was established between putative bacteria contributing to atheromatous plaques and species associated with periodontal disease. One particularly important study to be carried out is the investigation of a possible clinically meaningful reduction in coronary heart disease resulting from the prevention or treatment of periodontal disease.

  2. Bacterial sex in dental plaque

    OpenAIRE

    Olsen, Ingar; Tribble, Gena D; Fiehn, Nils-Erik; Wang, Bing-Yan

    2013-01-01

    Genes are transferred between bacteria in dental plaque by transduction, conjugation, and transformation. Membrane vesicles can also provide a mechanism for horizontal gene transfer. DNA transfer is considered bacterial sex, but the transfer is not parallel to processes that we associate with sex in higher organisms. Several examples of bacterial gene transfer in the oral cavity are given in this review. How frequently this occurs in dental plaque is not clear, but evidence suggests that it a...

  3. Denitrification in human dental plaque

    OpenAIRE

    Verstraete Willy; Heisterkamp Ines M; Gieseke Armin; Stief Peter; Schreiber Frank; de Beer Dirk; Stoodley Paul

    2010-01-01

    Abstract Background Microbial denitrification is not considered important in human-associated microbial communities. Accordingly, metabolic investigations of the microbial biofilm communities of human dental plaque have focused on aerobic respiration and acid fermentation of carbohydrates, even though it is known that the oral habitat is constantly exposed to nitrate (NO3-) concentrations in the millimolar range and that dental plaque houses bacteria that can reduce this NO3- to nitrite (NO2-...

  4. Cataractogenesis after Cobalt-60 eye plaque radiotherapy

    International Nuclear Information System (INIS)

    This study was designed to estimate the actuarial incidence of typical postirradiation cataracts and to identify prognostic factors related to their development in melanoma-containing eyes treated by Cobalt-60 plaque radiotherapy. A special interest was the impact of calculated radiation dose and dose-rate to the lens. The authors evaluated the actuarial occurrence of post-irradiation cataract in 365 patients with primary posterior uveal melanoma treated by Cobalt-60 plaque radiotherapy between 1976 and 1986. Only 22% (S.E. = 4.6%) of the patients who received a total dose of 6 to 20 Gy at the center of the lens developed a visually significant cataract attributable to the radiation within 5 years after treatment. Using multivariate Cox proportional hazards modeling, the authors identified thickness of the tumor, location of the tumor's anterior margin relative to the equatorward and the ora serrata, and diameter of the eye plaque used as the best combination of covariables for predicting length of time until development of cataract. Surprisingly, the dose of radiation delivered to the lens, which was strongly correlated to all of these covariables, was not a significant predictive factor in multivariate analysis. The results suggest that success of efforts to decrease the occurrence rate of post-irradiation cataracts by better treatment planning might be limited in patients with posterior uveal melanoma. 21 refs., 2 figs., 5 tabs

  5. Non-invasive detection of vulnerable coronary plaque

    OpenAIRE

    Faisal Sharif; Lohan, Derek G.; William Wijns

    2011-01-01

    Critical coronary stenoses have been shown to contribute to only a minority of acute coronary syndromes and sudden cardiac death. Autopsy studies have identified a subgroup of high-risk patients with disrupted vulnerable plaque and modest stenosis. Consequently, a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease. Recent advances in invasive and non-invasive imaging techniques have shown the potential to identi...

  6. MRI plaque imaging reveals high-risk carotid plaques especially in diabetic patients irrespective of the degree of stenosis

    Directory of Open Access Journals (Sweden)

    Holzer K

    2010-11-01

    Full Text Available Abstract Background Plaque imaging based on magnetic resonance imaging (MRI represents a new modality for risk assessment in atherosclerosis. It allows classification of carotid plaques in high-risk and low-risk lesion types (I-VIII. Type 2 diabetes mellitus (DM 2 represents a known risk factor for atherosclerosis, but its specific influence on plaque vulnerability is not fully understood. This study investigates whether MRI-plaque imaging can reveal differences in carotid plaque features of diabetic patients compared to nondiabetics. Methods 191 patients with moderate to high-grade carotid artery stenosis were enrolled after written informed consent was obtained. Each patient underwent MRI-plaque imaging using a 1.5-T scanner with phased-array carotid coils. The carotid plaques were classified as lesion types I-VIII according to the MRI-modified AHA criteria. For 36 patients histology data was available. Results Eleven patients were excluded because of insufficient MR-image quality. DM 2 was diagnosed in 51 patients (28.3%. Concordance between histology and MRI-classification was 91.7% (33/36 and showed a Cohen's kappa value of 0.81 with a 95% CI of 0.98-1.15. MRI-defined high-risk lesion types were overrepresented in diabetic patients (n = 29; 56.8%. Multiple logistic regression analysis revealed association between DM 2 and MRI-defined high-risk lesion types (OR 2.59; 95% CI [1.15-5.81], independent of the degree of stenosis. Conclusion DM 2 seems to represent a predictor for the development of vulnerable carotid plaques irrespective of the degree of stenosis and other risk factors. MRI-plaque imaging represents a new tool for risk stratification of diabetic patients. See Commentary: http://www.biomedcentral.com/1741-7015/8/78/abstract

  7. The ability of high dose rosuvastatin to improve plaque composition in non-intervened coronary arteries: Rationale and design of the Integrated Biomarker and Imaging Study-3 (IBIS-3)

    NARCIS (Netherlands)

    C. Simsek (Cihan); H.M. Garcia-Garcia (Hector); R.J.M. van Geuns (Robert Jan); M. Magro (Michael); C. Girasis (Chrysafios); N.M.D.A. van Mieghem (Nicolas); M.J. Lenzen (Mattie); S.P.M. de Boer (Sanneke); E.S. Regar (Eveline); W.J. van der Giessen (Wim); J. Raichlen (Joel); H.J. Duckers (Henricus); F. Zijlstra (Felix); T. van der Steen (Ton); H. Boersma (Eric); P.W.J.C. Serruys (Patrick)

    2012-01-01

    textabstractAims: Acute coronary syndromes (ACS) are often caused by rupture of non-flow limiting "vulnerable" atherosclerotic plaque, characterised by a large necrotic core pool and a thin, inflamed fibrous cap that are unidentifiable with diagnostic coronary angiography. The implementation of nove

  8. Coronary Computed Tomography Angiography Derived Fractional Flow Reserve and Plaque Stress

    DEFF Research Database (Denmark)

    Nørgaard, Bjarne Linde; Leipsic, Jonathon; Koo, Bon-Kwon;

    2016-01-01

    and physiologic modeling now enables simulation of patient-specific hemodynamic parameters including blood velocity, pressure, pressure gradients, and FFR from standard acquired coronary computed tomography (CT) datasets. In this review article, we describe the potential impact on clinical practice...... and the science behind noninvasive coronary computed tomography (CT) angiography derived fractional flow reserve (FFRCT) as well as future applications of this technology in treatment planning and quantifying forces on atherosclerotic plaques.......Fractional flow reserve (FFR) measured during invasive coronary angiography is an independent prognosticator in patients with coronary artery disease and the gold standard for decision making in coronary revascularization. The integration of computational fluid dynamics and quantitative anatomic...

  9. Optimization of 125I ophthalmic plaque brachytherapy

    International Nuclear Information System (INIS)

    Episcleral plaques containing 125I sources are often used in the treatment of ocular melanoma. Within four years post-treatment, however, the majority of patients experience some visual loss due to radiation retinopathy. The high incidence of late complications suggests that careful treatment optimization may lead to improved outcome. The goal of optimization would be to reduce the magnitude of vision-limiting complications without compromising tumor control. We have developed a three-dimensional computer model for ophthalmic plaque therapy which permits us to explore the potential of various optimization strategies. One simple strategy which shows promise is to maximize the ratio of dose to the tumor apex (T) compared to dose to the macula (M). By modifying the parameters of source location, activity distribution, source orientation, and shielding we find that the calculated T:M ratio can be varied by a factor of 2 for a common plaque design and posterior tumor location. Margins and dose to the tumor volume remain essentially unchanged

  10. Microbial Diversity Similarities in Periodontal Pockets and Atheromatous Plaques of Cardiovascular Disease Patients

    OpenAIRE

    Serra e Silva Filho, Wagner; Casarin, Renato C. V.; Nicolela Junior, Eduardo L.; Passos, Humberto M.; Antônio W Sallum; Gonçalves, Reginaldo B.

    2014-01-01

    Background and Objective The immune and infectious alterations occurring in periodontitis have been shown to alter the development and severity of cardiovascular disease. One of these relationships is the translocation of oral bacteria to atheroma plaques, thereby promoting plaque development. Thus, the aim of this study was to assess, by 16s cloning and sequencing, the microbial diversity of the subgingival environment and atheroma plaques of patients concomitantly suffering from periodontit...

  11. High-resolution multicontrast-weighted MR imaging from human carotid endarterectomy specimens to assess carotid plaque components

    International Nuclear Information System (INIS)

    The American Heart Association modified classification for atherosclerotic plaque lesions has defined vulnerable plaques as those prone to rupture. The aim of our study was to assess the sensitivity and specificity of 1.5-T magnetic resonance imaging (MRI) in the evaluation of the characteristics of plaque components. Twelve carotid endarterectomy specimens were imaged by ex-vivo high-resolution 1.5-T MRI. Thirty-four cross-section axial images were selected for pixel-by-pixel basis analysis to demonstrate the most significant tissue features. Data were then submitted for histopathological examination and each specimen analysed in the light of the histological components (lipid core, fibrous tissue, fibrous/loose connective tissue, calcifications). The overall sensitivity and specificity rates for each tissue type were, respectively, 92% and 74% for the lipid core, 82% and 94% for the fibrous tissue, 72% and 87% for the fibrous/loose connective tissue, and 98% and 99% for calcification. The use of 1.5-T MRI appears to be a reliable tool to characterise plaque components and could help in the screening of patients with high risk of plaque rupture. The possibility of applying MRI in clinical daily practice may change the non-invasive approach to carotid artery diagnostic imaging, thus allowing an early identification of patients with vulnerable plaques. (orig.)

  12. High-resolution multicontrast-weighted MR imaging from human carotid endarterectomy specimens to assess carotid plaque components

    Energy Technology Data Exchange (ETDEWEB)

    Fabiano, Sebastiano; Mancino, Stefano; Stefanini, Matteo; Chiocchi, Marcello; Simonetti, Giovanni [University ' ' Tor Vergata' ' , Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology, Nuclear Medicine and Radiotherapy, Rome (Italy); Mauriello, Alessandro; Spagnoli, Luigi Giusto [University ' ' Tor Vergata' ' , Department of Biopathology and Image Diagnostics, Institute of Anatomic Pathology, Rome (Italy)

    2008-12-15

    The American Heart Association modified classification for atherosclerotic plaque lesions has defined vulnerable plaques as those prone to rupture. The aim of our study was to assess the sensitivity and specificity of 1.5-T magnetic resonance imaging (MRI) in the evaluation of the characteristics of plaque components. Twelve carotid endarterectomy specimens were imaged by ex-vivo high-resolution 1.5-T MRI. Thirty-four cross-section axial images were selected for pixel-by-pixel basis analysis to demonstrate the most significant tissue features. Data were then submitted for histopathological examination and each specimen analysed in the light of the histological components (lipid core, fibrous tissue, fibrous/loose connective tissue, calcifications). The overall sensitivity and specificity rates