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Sample records for carotid atherosclerotic plaque

  1. 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.

  2. Imaging of the Fibrous Cap in Atherosclerotic Carotid Plaque

    International Nuclear Information System (INIS)

    Saba, Luca; Potters, Fons; Lugt, Aad van der; Mallarini, Giorgio

    2010-01-01

    In the last two decades, a substantial number of articles have been published to provide diagnostic solutions for patients with carotid atherosclerotic disease. These articles have resulted in a shift of opinion regarding the identification of stroke risk in patients with carotid atherosclerotic disease. In the recent past, the degree of carotid artery stenosis was the sole determinant for performing carotid intervention (carotid endarterectomy or carotid stenting) in these patients. We now know that the degree of stenosis is only one marker for future cerebrovascular events. If one wants to determine the risk of these events more accurately, other parameters must be taken into account; among these parameters are plaque composition, presence and state of the fibrous cap (FC), intraplaque haemorrhage, plaque ulceration, and plaque location. In particular, the FC is an important structure for the stability of the plaque, and its rupture is highly associated with a recent history of transient ischaemic attack or stroke. The subject of this review is imaging of the FC.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    ) and an additional ipsilateral internal carotid artery stenosis of greater than 60% were recruited. FDG uptake in the carotids was determined by PET/computed tomography and expressed as mean and maximal standardized uptake values (SUVmean and SUVmax). The atherosclerotic plaques were subsequently recovered...... by carotid endarterectomy. The gene expression of markers of vulnerability - CD68, IL-18, matrix metalloproteinase 9, cathepsin K, GLUT-1, and hexokinase type II (HK2) - were measured in plaques by quantitative PCR. RESULTS: In a multivariate linear regression model, GLUT-1, CD68, cathepsin K, and HK2 gene...... expression remained in the final model as predictive variables of FDG accumulation calculated as SUVmean (R=0.26, PK, and HK2 gene expression as independent predictive variables of FDG accumulation calculated...

  4. 3D Fiber Orientation in Atherosclerotic Carotid Plaques

    NARCIS (Netherlands)

    A.C. Akyildiz (Ali); C.-K. Chai (Chen-Ket); C.W.J. Oomens (Cees); A. van der Lugt (Aad); F.P.T. Baaijens (Frank); G.J. Strijkers (Gustav); F.J.H. Gijsen (Frank)

    2017-01-01

    textabstractAtherosclerotic plaque rupture is the primary trigger of fatal cardiovascular events. Fibrillar collagen in atherosclerotic plaques and their directionality are anticipated to play a crucial role in plaque rupture. This study aimed assessing 3D fiber orientations and architecture in

  5. Atherosclerotic carotid plaque assessment with multidetector computed tomography angiography

    NARCIS (Netherlands)

    T.T. de Weert (Thomas)

    2009-01-01

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

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

    NARCIS (Netherlands)

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

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

  7. Humanin, a cytoprotective peptide, is expressed in carotid atherosclerotic [corrected] plaques in humans.

    Science.gov (United States)

    Zacharias, David G; Kim, Sung Gyun; Massat, Alfonso Eirin; Bachar, Adi R; Oh, Yun K; Herrmann, Joerg; Rodriguez-Porcel, Martin; Cohen, Pinchas; Lerman, Lilach O; Lerman, Amir

    2012-01-01

    The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN) is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques. Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13% of plaque area, p<0.0001). These data were further confirmed by immunoblot (density of HN/β-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01). TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46% of nuclei, p<0.01). Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization), smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9. The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque.

  8. Atherosclerotic Carotid Plaques: Multimodality Imaging with Contrast-enhanced Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.

    Science.gov (United States)

    Hingwala, Divyata R; Chandrasekhakan, Kesavadas; Thomas, Bejoy; Sylaja, P N; Unnikrishnan, M; Kapilamoorthy, T R

    2017-01-01

    The imaging of carotid plaques has undergone a paradigm shift increasing importance being given to plaque characterization. Patients with "vulnerable" plaques are more prone to develop future neurovascular events. The purpose of this study is to analyze the role of multimodality imaging techniques in the assessment of carotid atherosclerotic plaques. Twenty-six patients were prospectively enrolled in the study. Patients underwent multidetector computed tomography (CT) angiography, ultrasound, contrast-enhanced ultrasound, and high-resolution magnetic resonance imaging (MRI) of the carotid arteries with special emphasis on the carotid bifurcation. The mean age of patients was 65.41 years. Twenty-one were males. Plaque neovascularization was seen in 10 of the 18 plaques studied (55.56%). Based on the predominant components of the plaque, plaques were characterized as lipid (3), lipid with recent hemorrhage (1), fibrous (7), fibrofatty (4), fibrofatty with some hemorrhagic components (3), and recent hemorrhage (2). Together, contrast-enhanced ultrasound, CT, and MRI provide complete information about the plaque characteristics.

  9. 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

  10. Symptomatic carotid atherosclerotic disease: correlations between plaque composition and ipsilateral stroke risk

    Science.gov (United States)

    Rothwell, Peter M; Redgrave, Jessica N; Moll, Frans L; de Vries, Jean-Paul PM; de Kleijn, Dominique PV; den Ruijter, Hester M; de Borst, Gert Jan; Pasterkamp, Gerard

    2014-01-01

    BACKGROUND AND PURPOSE For symptomatic patients with carotid artery stenosis the risk-benefit for surgical intervention may vary among patient groups. Various modalities of plaque imaging have been promoted as potential tools for additional risk stratification, particularly in patients with moderate stenosis. However, it remains uncertain to what extent carotid plaque components predict risk of future ipsilateral ischaemic stroke. METHODS In two large atherosclerotic carotid plaque biobank studies, we related histological characteristics of 1640 carotid plaques with a validated risk model for the prediction of individual 1- and 5-year stroke risk. RESULTS No significant heterogeneity between the studies was found. Predicted 5-year stroke risk (top versus bottom quartile) was related to plaque thrombus (OR=1.42, 95%CI 1.11-1.89, p=0.02), fibrous content (0.65, 0.49-0.87, p=0.004), macrophage infiltration (1.41, 1.05-1.90, p=0.02), high micro-vessel density (1.49, 1.05-2.11, p=0.03), and overall plaque instability (1.40, 1.05-1.87,p=0.02). This association was not observed for cap thickness, calcification, intra-plaque haemorrhage, or lymphocyte infiltration. Plaques removed within 30-days of most recent symptomatic event were most strongly correlated with predicted stroke risk. CONCLUSIONS Features of ‘the vulnerable carotid plaque’ including plaque thrombus, low fibrous content, macrophage infiltration and microvessel density correlate with predicted stroke risk. This study provides a basis for plaque imaging studies focused on stroke risk stratification. PMID:25477221

  11. Symptomatic carotid atherosclerotic disease: correlations between plaque composition and ipsilateral stroke risk.

    Science.gov (United States)

    Howard, Dominic Pj; van Lammeren, Guus W; Rothwell, Peter M; Redgrave, Jessica N; Moll, Frans L; de Vries, Jean-Paul Pm; de Kleijn, Dominique Pv; den Ruijter, Hester M; de Borst, Gert Jan; Pasterkamp, Gerard

    2015-01-01

    For symptomatic patients with carotid artery stenosis, the risk benefit for surgical intervention may vary among patient groups. Various modalities of plaque imaging have been promoted as potential tools for additional risk stratification, particularly in patients with moderate stenosis. However, it remains uncertain to what extent carotid plaque components predict risk of future ipsilateral ischemic stroke. In 2 large atherosclerotic carotid plaque biobank studies, we related histological characteristics of 1640 carotid plaques with a validated risk model for the prediction of individual 1- and 5-year stroke risk. No significant heterogeneity between the studies was found. Predicted 5-year stroke risk (top versus bottom quartile) was related to plaque thrombus (odds ratio, 1.42; 95% confidence interval, 1.11-1.89; P=0.02), fibrous content (0.65; 0.49-0.87; P=0.004), macrophage infiltration (1.41; 1.05-1.90; P=0.02), high microvessel density (1.49; 1.05-2.11; P=0.03), and overall plaque instability (1.40; 1.05-1.87; P=0.02). This association was not observed for cap thickness, calcification, intraplaque hemorrhage, or lymphocyte infiltration. Plaques removed within 30 days of most recent symptomatic event were most strongly correlated with predicted stroke risk. Features of the vulnerable carotid plaque, including plaque thrombus, low fibrous content, macrophage infiltration, and microvessel density, correlate with predicted stroke risk. This study provides a basis for plaque imaging studies focused on stroke risk stratification. © 2014 American Heart Association, Inc.

  12. Matrix metalloproteinase-2 of human carotid atherosclerotic plaques promotes platelet activation. Correlation with ischaemic events.

    Science.gov (United States)

    Lenti, Massimo; Falcinelli, Emanuela; Pompili, Marcella; de Rango, Paola; Conti, Valentina; Guglielmini, Giuseppe; Momi, Stefania; Corazzi, Teresa; Giordano, Giuseppe; Gresele, Paolo

    2014-06-01

    Purified active matrix metalloproteinase-2 (MMP-2) is able to promote platelet aggregation. We aimed to assess the role of MMP-2 expressed in atherosclerotic plaques in the platelet-activating potential of human carotid plaques and its correlation with ischaemic events. Carotid plaques from 81 patients undergoing endarterectomy were tested for pro-MMP-2 and TIMP-2 content by zymography and ELISA. Plaque extracts were incubated with gel-filtered platelets from healthy volunteers for 2 minutes before the addition of a subthreshold concentration of thrombin receptor activating peptide-6 (TRAP-6) and aggregation was assessed. Moreover, platelet deposition on plaque extracts immobilised on plastic coverslips under high shear-rate flow conditions was measured. Forty-three plaque extracts (53%) potentiated platelet aggregation (+233 ± 26.8%), an effect prevented by three different specific MMP-2 inhibitors (inhibitor II, TIMP-2, moAb anti-MMP-2). The pro-MMP-2/TIMP-2 ratio of plaques potentiating platelet aggregation was significantly higher than that of plaques not potentiating it (3.67 ± 1.21 vs 1.01 ± 0.43, p<0.05). Moreover, the platelet aggregation-potentiating effect, the active-MMP-2 content and the active MMP-2/pro-MMP-2 ratio of plaque extracts were significantly higher in plaques from patients who developed a subsequent major cardiovascular event. In conclusion, atherosclerotic plaques exert a prothrombotic effect by potentiating platelet activation due to their content of MMP-2; an elevated MMP-2 activity in plaques is associated with a higher rate of subsequent ischaemic cerebrovascular events.

  13. Humanin, a cytoprotective peptide, is expressed in carotid atherosclerotic [corrected] plaques in humans.

    Directory of Open Access Journals (Sweden)

    David G Zacharias

    Full Text Available The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques.Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13% of plaque area, p<0.0001. These data were further confirmed by immunoblot (density of HN/β-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01. TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46% of nuclei, p<0.01. Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization, smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9.The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque.

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

    DEFF Research Database (Denmark)

    van Engelen, Arna; Niessen, Wiro J.; Klein, Stefan

    2014-01-01

    Atherosclerotic plaque composition can indicate plaque vulnerability. We segment atherosclerotic plaque components from the carotid artery on a combination of in vivo MRI and CT-angiography (CTA) data using supervised voxelwise classification. In contrast to previous studies the ground truth...... for training is directly obtained from 3D registration with histology for fibrous and lipid-rich necrotic tissue, and with [Formula: see text]CT for calcification. This registration does, however, not provide accurate voxelwise correspondence. We therefore evaluate three approaches that incorporate uncertainty......), II) samples are weighted by the local contour distance of the lumen and outer wall between histology and in vivo data, and III) 10% of each class is rejected by Gaussian outlier rejection. Classification was evaluated on the relative volumes (% of tissue type in the vessel wall) for calcified...

  15. An integrated method for atherosclerotic carotid plaque segmentation in ultrasound image.

    Science.gov (United States)

    Qian, Chunjun; Yang, Xiaoping

    2018-01-01

    Carotid artery atherosclerosis is an important cause of stroke. Ultrasound imaging has been widely used in the diagnosis of atherosclerosis. Therefore, segmenting atherosclerotic carotid plaque in ultrasound image is an important task. Accurate plaque segmentation is helpful for the measurement of carotid plaque burden. In this paper, we propose and evaluate a novel learning-based integrated framework for plaque segmentation. In our study, four different classification algorithms, along with the auto-context iterative algorithm, were employed to effectively integrate features from ultrasound images and later also the iteratively estimated and refined probability maps together for pixel-wise classification. The four classification algorithms were support vector machine with linear kernel, support vector machine with radial basis function kernel, AdaBoost and random forest. The plaque segmentation was implemented in the generated probability map. The performance of the four different learning-based plaque segmentation methods was tested on 29 B-mode ultrasound images. The evaluation indices for our proposed methods were consisted of sensitivity, specificity, Dice similarity coefficient, overlap index, error of area, absolute error of area, point-to-point distance, and Hausdorff point-to-point distance, along with the area under the ROC curve. The segmentation method integrated the random forest and an auto-context model obtained the best results (sensitivity 80.4 ± 8.4%, specificity 96.5 ± 2.0%, Dice similarity coefficient 81.0 ± 4.1%, overlap index 68.3 ± 5.8%, error of area -1.02 ± 18.3%, absolute error of area 14.7 ± 10.9%, point-to-point distance 0.34 ± 0.10 mm, Hausdorff point-to-point distance 1.75 ± 1.02 mm, and area under the ROC curve 0.897), which were almost the best, compared with that from the existed methods. Our proposed learning-based integrated framework investigated in this study could be useful for

  16. The relationship between serum paraoxonase levels and carotid atherosclerotic plaque formation in Alzheimer's patients.

    Science.gov (United States)

    Arslan, Ayşe; Tüzün, Fatma Aykan; Arslan, Harun; Demir, Halit; Tamer, Sibel; Demir, Canan; Tasin, Muhterem

    Low paraoxonase 1 (PON1) activity and carotid atherosclerosis have been suggested to be important risk factors for dementia. However, the studies to date could not fully clarify the relationship between PON1, carotid atherosclerosis and dementia. The present study aimed to measure carotid atherosclerosis and PON1 activity in Alzheimer's Disease and to evaluate the relationship between them. The study included 25 Alzheimer's patients and 25 control subjects, for a total of 50 individuals. The study measured the serum PON1 activity and other biochemical parameters and carotid atherosclerotic plaque values of the participants. The mean paraoxonase activity (31.06±2.31U/L) was significantly lower in the Alzheimer's group compared to the control group (59.05±7.05U/L) (Phomocystein level was higher in the patient group (22.15±7.05) compared to the control group (13.30±3.32). In conclusion, our findings show inverse association between PON1 activity and carotid atherosclerosis in Alzheimer patients: the lower the PON1 activity the more progressed the atherosclerotic process in AD. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

  18. 64Cu-DOTATATE PET/MRI for detection of activated macrophages in carotid atherosclerotic plaques

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  1. Leptomeningeal collateral vessels are a major risk factor for intracranial hemorrhage after carotid stenting in patients with carotid atherosclerotic plaque.

    Science.gov (United States)

    Lee, Kang Ji; Kwak, Hyo Sung; Chung, Gyung Ho; Song, Ji Soo; Hwang, Seung Bae

    2016-05-01

    To evaluate the relationship between leptomeningeal collaterals and intracranial hemorrhage (ICH) after carotid artery stenting (CAS). A retrospective study was undertaken of 228 patients (median age 75 years (range 44-90); 187 men and 41 women) who underwent CAS due to unilateral carotid atherosclerotic plaque from January 2009 to December 2013. Cerebral angiographic findings were classified into three patterns: type I, normal visualization of the anterior and middle cerebral arteries without leptomeningeal collaterals; type II, visualization of the middle cerebral artery only without leptomeningeal collaterals; and type III, visualization of leptomeningeal collateral flow. For all cerebral angiographic findings, 146 (64.0%) were type I, 61 (26.8%) were type II, and 21 (9.2%) were type III. Four patients (1.8%) died with fatal ICH after CAS and had type III angiographic findings (19%). The prevalence of ICH in patients with leptomeningeal collateral vessels was significantly higher than in patients without leptomeningeal collateral vessels (19% vs 0%, pcollateral vessels are a major risk factor for ICH after CAS in patients with carotid atherosclerotic plaque. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Determinants of carotid atherosclerotic plaque burden in a stroke-free population

    NARCIS (Netherlands)

    Selwaness, Mariana; Hameeteman, Reinhard; Van 't Klooster, Ronald; Van den Bouwhuijsen, Quirijn; Hofman, Albert; Franco, Oscar H.; Niessen, W.J.; Klein, Stefan; Vernooij, Meike W.; Van Der Lugt, Aad; Wentzel, Jolanda J.

    2016-01-01

    Background and aims In a large stroke-free population, we sought to identify cardiovascular risk factors and carotid plaque components associated with carotid plaque burden, lumen volume and stenosis. Methods The carotid arteries of 1562 stroke-free participants from The Rotterdam Study were

  3. 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.

    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...

  4. Echo-lucency 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 Moes; Nordestgaard, Børge G.; Weibe, Brit M.

    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...

  5. Effect of atorvastatin calcium on the carotid atherosclerotic plaque and cerebral blood flow indicators in patients with TIA

    Directory of Open Access Journals (Sweden)

    Jing Gao

    2017-01-01

    Full Text Available Objective: To explore the effect of atorvastatin calcium on the carotid atherosclerotic plaque, serum lipid level, and cerebral hemodynamic indicators in patients with transient ischemic attack (TIA. Methods: A total of 80 patients with TIA and carotid atherosclerotic plaque who were admitted in our hospital and confirmed by the ultrasound were included in the study and randomized into the treatment group and the control group (n = 40. The patients in the two groups were given TIA routine treatments and aspirin. On this basis, the patients in the treatment group were given atorvastatin calcium. The carotid ultrasound before treatment and 6 months after treatment in the two groups was performed to compare the atherosclerotic plaque area and IMT. The serum lipid level and cerebral hemodynamic parameters were detected. Results: IMT and carotid plaque area after treatment in the treatment group were significantly reduced when compared with before treatment (P0.05. TC, TG, and LDL levels after treatment were significantly reduced when compared with before treatment (P<0.05, while HDL level was significantly elevated when compared with before treatment (P<0.05. TC, TG, and LDL levels after treatment in the treatment group were significantly lower than those in the control group (P<0.05, while HDL level was significantly higher than that in the control group (P<0.05. The average blood velocity and average blood flow volume of cerebral circulation after treatment in the treatment group were significantly higher than those in the control group (P<0.05, while the cerebrovascular characteristic resistance and peripheral resistance were significantly lower than those in the control group (P<0.05. Conclusions: Atorvastatin calcium in the treatment of TIA can significantly reduce the serum lipid level, alleviate or stabilize the carotid atherosclerotic

  6. Carotid Atherosclerotic Plaque Characteristics on Magnetic Resonance Imaging Relate With History of Stroke and Coronary Heart Disease.

    Science.gov (United States)

    Selwaness, Mariana; Bos, Daniel; van den Bouwhuijsen, Quirijn; Portegies, Marileen L P; Ikram, M Arfan; Hofman, Albert; Franco, Oscar H; van der Lugt, Aad; Wentzel, Jolanda J; Vernooij, Meike W

    2016-06-01

    Because atherosclerosis is a systemic disease, presence and composition on 1 location may relate to ischemic events in distant locations. We examined whether carotid atherosclerotic wall thickness, stenosis, and plaque composition are related to history of ischemic stroke and coronary heart disease (CHD). From the population-based Rotterdam Study, 1731 asymptomatic participants (mean age, 72.4±9.1 years; 55% males) underwent magnetic resonance imaging of both carotid arteries. We assessed carotid wall thickness, stenosis and plaque composition, that is presence of intraplaque hemorrhage, lipid, and calcification. History of ischemic stroke and CHD was assessed until date of magnetic resonance imaging. The study was approved by the institutional review board, and all participants gave informed consent. Logistic regression analyses adjusted for age and traditional cardiovascular risk factors were used to study sex-specific associations between plaque characteristics and clinical events. We found that both carotid stenosis and intraplaque hemorrhage were associated with ischemic stroke in men but not in women (men: odds ratio [OR] for stenosis [per 10% increase]: 1.17 [95% CI, 1.06-1.30] and for intraplaque hemorrhage 2.39 [95% CI, 1.32-4.35]). In both men and women, carotid stenosis was associated with CHD (men: OR per 10% increase 1.12 [95% CI, 1.04-1.21] and women: OR, 1.17 [95% CI, 1.03-1.34]) and carotid wall thickness was associated with CHD (men: OR, 1.20 [95% CI, 1.03-1.39] and women: OR, 1.21 [95% CI, 0.88-1.65]). None of the plaque components was associated with CHD. Whereas carotid plaque thickness and stenosis are associated with the history of ischemic stroke and CHD, carotid intraplaque hemorrhage is associated with ischemic stroke, but not with CHD, providing novel insights into the pathogenesis of cardiovascular events. © 2016 American Heart Association, Inc.

  7. Statin treatment is associated with reduced toll-like receptor 4 immunohistochemical expression on carotid atherosclerotic plaques: a novel effect of statins.

    Science.gov (United States)

    Katsargyris, Athanasios; Klonaris, Chris; Tsiodras, Sotirios; Bastounis, Elias; Giannopoulos, Athanasios; Theocharis, Stamatios

    2011-12-01

    Toll-like receptor 4 (TLR4) has been recently implicated in inflammatory pathways involved in carotid plaque destabilization. Given that statins have plaque stabilization and inflammation reduction effects, we investigated whether TLR4 expression on carotid atherosclerotic plaques correlates with statin intake. Carotid atherosclerotic plaques were obtained on 140 patients (preoperative statin intake, n = 70). TLR4 immunohistochemical expression was investigated in endothelial cells (ECs), macrophages (MACs) and smooth muscle cells (SMCs) of carotid atheroma. TLR4 positivity, over-expression and intensity of immunostaining were compared in statin versus no-statin users. The results of this study showed that statin users had a significantly lower expression of TLR4 in ECs (P = 0.02, 0.001, 0.006 for TLR4 positivity, increased intensity and over-expression, respectively). Similarly, TLR4 positivity was less pronounced in carotid plaque MACs of statin users (P = 0.03). No carotid specimen with increased EC TLR4 intensity or over-expression was observed among statin users. The prevalence of any cerebrovascular accident was 61.4% in the 'no statin' versus 18.6% in the 'statin' group (odds ratio for statin use: 0.14, 95% CI: 0.07-0.31, P < 0.001). In conclusion, statin treatment is associated with attenuated TLR4 expression on human carotid atherosclerotic plaques and a reduced risk of carotid-related cerebrovascular events. TLR4 may potentially mediate statins' plaque stabilization effects. Further investigation is necessary.

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

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    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.

  9. 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.

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

    International Nuclear Information System (INIS)

    Fagerberg, Björn; Barregard, Lars; Sallsten, Gerd; Forsgard, Niklas; Östling, Gerd; Persson, Margaretha; Borné, Yan

    2015-01-01

    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

  11. Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol

    Directory of Open Access Journals (Sweden)

    Walter Masson

    Full Text Available Abstract Background: Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance or with high remnant cholesterol levels could have a greater residual cardiovascular risk. Objectives: To determine the prevalence of lipid discordance in a primary prevention population and analyze the clinical variables associated with it; To investigate the association between lipid discordance and remnant cholesterol with the presence of carotid plaque. Methods: Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define “lipid discordance” if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were < 4.0 mmol/L. Ultrasound was used to assess carotid plaque occurrence. Multiple regression logistic models were performed. Results: The study included 772 patients (mean age 52 ± 11 years, 66% women. The prevalence of lipid discordance was 34%. Male sex and body mass index were independently associated with discordant lipid pattern. The prevalence of carotid plaque was higher in subjects with lipid discordance (40.2% vs. 29.2, p = 0.002. The multivariate analysis showed that the discordant lipid pattern was associated with the greater probability of carotid plaque (OR 1.58, 95% CI 1.08-2.34, p = 0.02. Similarly, a significant association between calculated remnant cholesterol and carotid plaque was found. Conclusion: Lipid discordance and presence of a higher level of calculated remnant cholesterol are associated with subclinical atherosclerosis. Our findings could be used to improve the residual cardiovascular risk evaluation.

  12. 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.)

  13. 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)

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

    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 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.)

  14. Advances in the research of high-resolution magnetic resonance imaging used for treating carotid atherosclerotic plaques in ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Xiao-nan ZHANG

    2014-01-01

    Full Text Available Stroke causespermanent neurological damage and death and badly endangers human's life and health. Ischemic stroke with the pathological basis of atherosclerotic lesions is the major type of stroke. Thus, early and timely detection of plaque vulnerability has become more and more important. As a noninvasive examination, carotid magnetic resonance imaging (MRI has tremendous advantages on detecting the characteristics of atherosclerotic plaque, such as high sensitivity and specificity on the plaque morphology and composition as well as hierarchical evaluation on the risk of plaque rupture, and furthermore provides significant imaging support on clinical treatments.

  15. All-optical extravascular laser-ultrasound and photoacoustic imaging of calcified atherosclerotic plaque in excised carotid artery

    Directory of Open Access Journals (Sweden)

    Jami L. Johnson

    2018-03-01

    Full Text Available Photoacoustic (PA imaging may be advantageous as a safe, non-invasive imaging modality to image the carotid artery. However, calcification that accompanies atherosclerotic plaque is difficult to detect with PA due to the non-distinct optical absorption spectrum of hydroxyapatite. We propose reflection-mode all-optical laser-ultrasound (LUS imaging to obtain high-resolution, non-contact, non-ionizing images of the carotid artery wall and calcification. All-optical LUS allows for flexible acquisition geometry and user-dependent data acquisition for high repeatability. We apply all-optical techniques to image an excised human carotid artery. Internal layers of the artery wall, enlargement of the vessel, and calcification are observed with higher resolution and reduced artifacts with nonconfocal LUS compared to confocal LUS. Validation with histology and X-ray computed tomography (CT demonstrates the potential for LUS as a method for non-invasive imaging in the carotid artery. Keywords: Atherosclerosis, Photoacoustic imaging, Laser-ultrasound, Calcification, Reverse-time migration

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

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    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

  17. Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol.

    Science.gov (United States)

    Masson, Walter; Lobo, Martín; Molinero, Graciela; Siniawski, Daniel

    2017-06-01

    Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance) or with high remnant cholesterol levels could have a greater residual cardiovascular risk. To determine the prevalence of lipid discordance in a primary prevention population and analyze the clinical variables associated with it; To investigate the association between lipid discordance and remnant cholesterol with the presence of carotid plaque. Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define "lipid discordance" if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were aterosclerose subclínica. Nossos achados podem ser usados para aprimorar a avaliação de risco cardiovascular residual.

  18. Atorvastatin treatment and carotid plaque morphology in first-ever atherosclerotic transient ischemic attack/stroke: a case-control study.

    Science.gov (United States)

    Marchione, Pasquale; Vento, Claudio; Morreale, Manuela; Izzo, Chiara; Maugeri, Andrea; Manuppella, Federica; Romeo, Tommaso; Giacomini, Patrizia

    2015-01-01

    A relationship between echolucency of carotid plaques and the consequent risk of ipsilateral ischemic stroke has been observed. An aggressive lipid-lowering therapy may increase the echogenicity of carotid plaque in patients with elevated low-density lipoprotein cholesterol levels. The aim of this study is to prospectively evaluate the long-term effect of high-dose atorvastatin on carotid plaque morphology in patients with first-ever transient ischemic attack or stroke. All patients with symptomatic first ischemic atherosclerotic cerebrovascular event occurred within the previous 10 days were enrolled. Carotid Doppler ultrasound of the neck vessels with 7-11 MHz probe for the definition of the atherosclerotic carotid framework was performed. The analysis of the gray-scale median (GSM) of each plate was carried out with image processing software. A total of 240 symptomatic plaques were included and divided into 3 groups: 80 in group A (atorvastatin 80 mg), 80 in group B (atorvastatin 40 mg), and 80 to group C (no atorvastatin). GSM score increases significantly more extensive in group A than in group B (+48.65 vs. +39.46, P < .02) and group C (+48.65 vs. 19.3, P = .0002). An inverse association between reduction of low-density lipoprotein and the increase in the GSM score (r = -.456, P = .007) has been observed. Moreover, the reduction of high-sensitive C-reactive protein correlates inversely with the increase of the GSM (r = -.398, P = .021). Dose-dependent effect of atorvastatin on symptomatic carotid plaque morphology may suggest a specific role of this drug in the atherosclerotic stroke prevention. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. High Field Atherosclerotic Plaque MRI

    OpenAIRE

    Yuan, Chun; Wang, Jinnan; Balu, Niranjan

    2012-01-01

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

  20. PLACD-7T Study: Atherosclerotic Carotid Plaque Components Correlated with Cerebral Damage at 7 Tesla Magnetic Resonance Imaging.

    Science.gov (United States)

    den Hartog, A G; Bovens, S M; Koning, W; Hendrikse, J; Pasterkamp, G; Moll, F L; de Borst, G J

    2011-02-01

    In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero-Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Comparison between a new computer program and the reference software for gray-scale median analysis of atherosclerotic carotid plaques.

    Science.gov (United States)

    Casella, Ivan Benaduce; Fukushima, Rodrigo Bono; Marques, Anita Battistini de Azevedo; Cury, Marcus Vinícius Martins; Presti, Calógero

    2015-03-01

    To compare a new dedicated software program and Adobe Photoshop for gray-scale median (GSM) analysis of B-mode images of carotid plaques. A series of 42 carotid plaques generating ≥50% diameter stenosis was evaluated by a single observer. The best segment for visualization of internal carotid artery plaque was identified on a single longitudinal view and images were recorded in JPEG format. Plaque analysis was performed by both programs. After normalization of image intensity (blood = 0, adventitial layer = 190), histograms were obtained after manual delineation of plaque. Results were compared with nonparametric Wilcoxon signed rank test and Kendall tau-b correlation analysis. GSM ranged from 00 to 100 with Adobe Photoshop and from 00 to 96 with IMTPC, with a high grade of similarity between image pairs, and a highly significant correlation (R = 0.94, p < .0001). IMTPC software appears suitable for the GSM analysis of carotid plaques. © 2014 Wiley Periodicals, Inc.

  3. Targeted folate receptor β fluorescence imaging as a measure of inflammation to estimate vulnerability within human atherosclerotic carotid plaque

    NARCIS (Netherlands)

    Jager, Nynke A.; Westra, Johanna; van Dam, Gooitzen M.; Teteloshvili, Nato; Tio, Rene A.; Breek, Jan-Cees; Slart, Riemer H. J. A.; Boersma, Hendrikus H.; Low, Phillip S.; Bijl, Marc; Zeebregts, Clark J.

    UNLABELLED: The probability of atherosclerotic plaque rupture and its thrombotic sequelae are thought to be increased at sites of macrophage accumulation. Folate receptor β (FR-β) is present on activated macrophages but not on quiescent macrophages or other immune cells. By conjugating the ligand

  4. Carotid atherosclerotic plaque progression and change in plaque composition over time: A 5-year follow-up study using serial ct angiography

    NARCIS (Netherlands)

    M.J. van Gils (Marjon); D. Vukadinovic (Danijela); A.C. Nouwens- van Dijk (Anouk); D.W.J. Dippel (Diederik); W.J. Niessen (Wiro); A. van der Lugt (Aad)

    2012-01-01

    textabstractBACKGROUND AND PURPOSE: Serial in vivo imaging of atherosclerosis is important for understanding plaque progression and is potentially useful in predicting cardiovascular events and monitoring treatment efficacy. This prospective study aims to quantify temporal changes in carotid

  5. CAROTID ATHEROSCLEROTIC LESION IN YOUNG PATIENTS

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    N. V. Pizova

    2014-01-01

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

  6. 3D reconstruction of carotid atherosclerotic plaque: comparison between spatial compound ultrasound models and anatomical models

    DEFF Research Database (Denmark)

    Lind, Bo L.; Fagertun, Jens; Wilhjelm, Jens E.

    2007-01-01

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

  7. 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

  8. 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

    This paper presents a quantitative comparison of three types of information available for 52 patients scheduled for carotid endarterectomy: subjective classification of the ultrasound images obtained during scanning before operation, first- and second-order statistical features extracted from...... 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...

  9. 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

  10. 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......-density lipoprotein cholesterol, hypertension, diabetes mellitus, smoking, C-reactive protein, plaque, and IMT. In contrast, high-density lipoprotein cholesterol, triglycerides, height, and leukocyte count were not significantly associated with AS (P>0.05). After adjustments, IMT, plaque, age, smoking, C...

  11. Influence of material property variability on the mechanical behaviour of carotid atherosclerotic plaques: a 3D fluid-structure interaction analysis.

    Science.gov (United States)

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

    2015-08-01

    Mechanical analysis has been shown to be complementary to luminal stenosis in assessing atherosclerotic plaque vulnerability. However, patient-specific material properties are not available and the effect of material properties variability has not been fully quantified. Media and fibrous cap (FC) strips from carotid endarterectomy samples were classified into hard, intermediate and soft according to their incremental Young's modulus. Lipid and intraplaque haemorrhage/thrombus strips were classified as hard and soft. Idealised geometry-based 3D fluid-structure interaction analyses were performed to assess the impact of material property variability in predicting maximum principal stress (Stress-P1 ) and stretch (Stretch-P1 ). When FC was thick (1000 or 600 µm), Stress-P1 at the shoulder was insensitive to changes in material stiffness, whereas Stress-P1 at mid FC changed significantly. When FC was thin (200 or 65 µm), high stress concentrations shifted from the shoulder region to mid FC, and Stress-P1 became increasingly sensitive to changes in material properties, in particular at mid FC. Regardless of FC thickness, Stretch-P1 at these locations was sensitive to changes in material properties. Variability in tissue material properties influences both the location and overall stress/stretch value. This variability needs to be accounted for when interpreting the results of mechanical modelling. © 2015 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

  12. 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.

  13. Comparison of carotid atherosclerotic plaque characteristics between patients with first-time and recurrent acute ischaemic stroke using B-mode ultrasound.

    Science.gov (United States)

    Li, Jin; Mi, Donghua; Pu, Yuehua; Zou, Xinying; Pan, Yuesong; Soo, Yannie; Leung, Thomas; Wang, Yilong; Wong, Ka Sing; Liu, Liping

    2015-06-23

    The differences between initial and recurrent stroke plaques are not defined. Hence, a nested case-control study was conducted to evaluate the association of stroke recurrence with the echogenic characteristics of carotid plaques in patients with ischaemic stroke. One hundred and four patients with 1-year recurrent acute ischaemic stroke were enrolled and compared with 104 control patients (first-time ischaemic stroke) matched for age, gender, stroke severity and treatment allocation. Based on the Mannheim Carotid Intima-Media Thickness Consensus (2004-2006), the number of carotid plaques and echogenicity between the two groups of patients were compared. As compared to patients with first-time stroke, those with recurrent stroke showed significantly higher prevalence of heart disease (13.46 vs 28.85%, P = 0.0066) and presence of intracranial stenosis (55.77 vs 89.90%, P stroke had a significantly higher rate of unstable plaques (80.41%) than patients with first-time stroke (64.21%, P = 0.036). Also, patients with recurrent stroke had a significantly larger number of plaques than patients with first-time stroke (P = 0.0152). Multivariate conditional logistic regression analysis (after adjustment for heart disease and intracranial stenosis) identified an association between 1-year stroke recurrence and the presence of unstable plaques (hazard ratio 3.077; 95% CI: 1.133-8.355). Stroke recurrence is related to advanced atherosclerosis defined by carotid plaque and its characteristics.

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

    NARCIS (Netherlands)

    Reuwer, Anne; van Eijk, Marco; Houttuijn-Bloemendaal, Felicia; van der Loos, Chris; Claessen, Nike; Teeling, Peter; Kastelein, J. J.; Hamann, Jörg; Goffin, Vincent; von der Thüsen, Jan; Twickler, Marcel; Aten, Jan

    2011-01-01

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

  15. Texture Analysis in Ultrasound Images of Carotid Plaque Components of Asymptomatic and Symptomatic Subjects

    OpenAIRE

    Loizou , Christos ,; Pantziaris , Marios; Theofilou , Marilena; Kasparis , Takis; Kyriakou , Efthivoulos

    2013-01-01

    Part 8: Third Workshop on Artificial Intelligence Applications in Biomedicine (AIAB 2013); International audience; There are indications that the texture of certain components of atherosclerotic carotid plaques in the common carotid artery (CCA), obtained by high resolution ultrasound imaging, may have additional prognostic implication for the risk of stroke. The objective of this study was to perform texture analysis of the middle component of atherosclerotic carotid plaques in 230 CCA plaqu...

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

    OpenAIRE

    Canton, Gador; Chiu, Bernard; Chen, Huijun; Chen, Yimin; Hatsukami, Thomas S.; Kerwin, William S.; Yuan, Chun

    2013-01-01

    Local hemodynamic forces, such as wall shear stress, are thought to trigger cellular and molecular mechanisms that determine atherosclerotic plaque vulnerability to rupture. Magnetic resonance imaging (MRI) 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 (CFD) has allowed researchers to obtain time-resolv...

  17. Macrophage heterogeneity in human carotid artery atherosclerotic plaques: identification of novel markers for M1 and M2 that are independent of the activation status

    NARCIS (Netherlands)

    Tits, van L.J.; Stienstra, Rinke; Netea, M.G.; Pol, J.A.; Truijers, M.; Vliet, van der J.A.; Hooiveld, Guido; Joosten, L.A.; Stalenhoef, A.F.

    2016-01-01

    Recent studies suggest the presence of both “classically activated” M1 and “alternatively activated” M2 macrophages in human atherosclerotic tissue, yet due to the lack of validated markers the reported localization patterns of these macrophage phenotypes within plaques are ambiguous. In the present

  18. Serum elastase activity, serum elastase inhibitors, and occurrence of carotid atherosclerotic plaques: the Etude sur le Vieillissement Artériel (EVA) study.

    Science.gov (United States)

    Zureik, Mahmoud; Robert, Ladislas; Courbon, Dominique; Touboul, Pierre-Jean; Bizbiz, Latifa; Ducimetière, Pierre

    2002-06-04

    In the last decades, interest has increased in the potential deleterious atherogenic effects of some cellular elastase activities. The results of experimental and clinical investigations were inconsistent. In this report, we assessed the associations of serum elastase activity and serum elastase inhibitors with carotid plaque occurrence during the 4-year follow-up in a population of 859 subjects free of coronary heart disease and stroke (age, 59 to 71 years). Serum elastase activity and serum elastase inhibitors were measured at baseline examination. Carotid B-mode ultrasound examination was performed at baseline and 2 years and 4 years later. The occurrence of carotid plaques in subjects with the lowest serum elastase activity values (quartile 1), in those with the intermediate values (quartiles 2 to 3), and in those with the highest values (quartile 4) was, respectively, 24.6%, 18.9%, and 12.2% (P<0.001 for trend). The multivariate odds ratios of carotid plaque occurrence associated with the three groups (adjusted for major known cardiovascular risk factors) were, respectively, 1.00, 0.67 (CI, 0.44 to 1.02; P<0.06), and 0.40 (CI, 0.23 to 0.70, P<0.001). For serum elastase inhibitors, the occurrence of carotid plaques in quartile 1 (lowest values), quartiles 2 to 3, and quartile 4 (highest values) was, respectively, 11.7%, 18.8%, and 25.2% (P for trend<0.001). The corresponding multivariate adjusted odds ratios were 1.00, 1.98 (CI, 1.19 to 3.31, P<0.01), and 3.18 (CI, 1.80 to 5.60, P<0.001). Low values of serum elastase activity and high values of serum elastase inhibitors were strongly and independently associated with increased 4-year carotid plaque occurrence. Further studies are necessary to elucidate the nature of the associations between elastase parameters and atherosclerosis.

  19. Data on consistency among different methods to assess atherosclerotic plaque echogenicity on standard ultrasound and intraplaque neovascularization on contrast-enhanced ultrasound imaging in human carotid artery

    Directory of Open Access Journals (Sweden)

    Mattia Cattaneo

    2016-12-01

    Full Text Available Here we provide the correlation among different carotid ultrasound (US variables to assess echogenicity n standard carotid US and to assess intraplaque neovascularization on contrast enhanced US. We recruited 45 consecutive subjects with an asymptomatic≥50% carotid artery stenosis. Carotid plaque echogenicity at standard US was visually graded according to Gray–Weale classification (GW and measured by the greyscale median (GSM, a semi-automated computerized measurement performed by Adobe Photoshop®. On CEUS imaging IPNV was graded according to the visual appearance of contrast within the plaque according to three different methods: CEUS_A (1=absent; 2=present; CEUS_B a three-point scale (increasing IPNV from 1 to 3; CEUS_C a four-point scale (increasing IPNV from 0 to 3. We have also implemented a new simple quantification method derived from region of interest (ROI signal intensity ratio as assessed by QLAB software. Further information is available in “Contrast-enhanced ultrasound imaging of intraplaque neovascularization and its correlation to plaque echogenicity in human carotid arteries atherosclerosis (M. Cattaneo, D. Staub, A.P. Porretta, J.M. Gallino, P. Santini, C. Limoni et al., 2016 [1].

  20. MRI-based biomechanical parameters for carotid artery plaque vulnerability assessment

    NARCIS (Netherlands)

    Speelman, Lambert; Teng, Zhongzhao; Nederveen, Aart J.; van der Lugt, Aad; Gillard, Jonathan H.

    2016-01-01

    Carotid atherosclerotic plaques are a major cause of ischaemic stroke. The biomechanical environment to which the arterial wall and plaque is subjected to plays an important role in the initiation, progression and rupture of carotid plaques. MRI is frequently used to characterize the morphology of a

  1. MR chemical shift imaging and spectroscopy of atherosclerotic plaque

    International Nuclear Information System (INIS)

    Vinitski, S.; Consigny, P.M.; Shapiro, M.J.; Janes, N.; Smullens, S.N.; Rifkin, M.D.

    1989-01-01

    The purpose of this study was to develop a technique for in vivo imaging and characterization of atherosclerotic plaque. The authors used a spin-echo technique with a short echo time (TE) of 11 msec. Lipid/water suppression was achieved by means of hybrid chemical shift imaging. Lesions were induced in three rabbits by a combination of balloon denudation of the abdominal aorta and a high-cholesterol diet. Following in vivo imaging of these rabbit aortas and human carotid arteries (1.5 T), the animals were killed or carotid endarterectomy was performed so that the plaques could be excised. The plaques were then analyzed in vitro both histologically and with high-resolution spectroscopy (8.5 T). Use of the short TE improved lesion visualization. The fat/water suppression showed only a small amount of mobile lipids in plaque. Both MR spectroscopic and histologic analysis corroborated these images. The composition of atherosclerotic plaques in both humans and rabbits was demonstrated to be heterogeneous, with predominantly nonmobile lipids. These results suggest that the combination of short TE MR imaging and fat/water suppression can identify plaque and delineate areas containing mobile lipids

  2. Mechanical Stresses in Carotid Plaques

    DEFF Research Database (Denmark)

    Samuel, Samuel Alberg

    simulationer, som tillod beregning af longitudinelle stress-niveauer i den fibrøse kappe. Afhandlingen indeholder tre artikler, som beskriver denne metode. Den første; “Mechanical Stresses in Carotid Plaques using MRI-Based Fluid Structure Interaction Models”, beskriver i detaljer metoden til at danne de...

  3. 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 comput...

  4. Carotid plaque thickness and carotid plaque burden predict future cardiovascular events in asymptomatic adult Americans

    DEFF Research Database (Denmark)

    Sillesen, Henrik; Sartori, Samantha; Sandholt, Benjamin

    2018-01-01

    Introduction: Prediction of cardiovascular events improves using imaging, i.e. coronary calcium score and ultrasound assessment of carotid plaque. This study analysed the predictive value of two ultrasound measures of carotid plaque size: carotid plaque thickness and carotid and intima-media thic...

  5. Induced macrophage activation in live excised atherosclerotic plaque.

    Science.gov (United States)

    Prebble, Hannah; Cross, Sean; Marks, Edward; Healy, Joe; Searle, Emily; Aamir, Raja; Butler, Anthony; Roake, Justin; Hock, Barry; Anderson, Nigel; Gieseg, Steven P

    2018-03-23

    Atherosclerotic plaques are complex tissues containing many different cell types. Macrophages contribute to inflammation, formation of the necrotic core, and plaque rupture. We examined whether macrophages in plaque can be activated and compared this to monolayer cells. The volume of calcium in the plaque was compared to the level of macrophage activation measured by total neopterin output. Carotid plaque samples were cut into 3 mm sections and cultured for up to 96 h. Live sections were stimulated with interferon-γ, phytohaemagglutinin or phorbol 12-myristate 13-acetate. Macrophage activation and oxidative stress were monitored by total neopterin (oxidized and non-oxidized 7,8-dihydroneopterin) and neopterin levels every 24 h for up to 4 d. The calcium content of two plaques was investigated by spectral imaging. Direct stimulation of macrophages in plaque sections with interferon-γ caused a sustained increase in neopterin (p = .037) and total neopterin (p = .003). The addition of phorbol 12-myristate 13-acetate to plaque had no significant effect on total neopterin production (p = .073) but increased neopterin (p = .037) whereas phytohaemagglutinin caused a significant increase in both neopterin and total neopterin (p = .0279 and .0168). There was an inverse association (R 2  = 0.91) between the volume of calcium and macrophage activation as measured by total neopterin production in stimulated plaque tissue. Resident macrophages within excised carotid plaque activated either directly or indirectly generate the biomarkers 7,8-dihydroneopterin and neopterin. Macrophage activation rather than the oxidative environment is associated with plaque calcification. Copyright © 2018 Elsevier GmbH. All rights reserved.

  6. Mechanical stresses in carotid plaques using MRI-based fluid-structure interaction models

    DEFF Research Database (Denmark)

    Kock, Samuel A; Nygaard, Jens Vinge; Eldrup, Nikolaj

    2008-01-01

    fluid-structure interaction (FSI) simulations of carotid atherosclerotic plaques were performed facilitating in-vivo estimation of longitudinal internal fibrous cap stresses. The FSI simulation combined finite element analysis (FEA) with computational fluid dynamics (CFD) simulations of blood...

  7. Cartilage oligomeric matrix protein (COMP) in murine brachiocephalic and carotid atherosclerotic lesions.

    Science.gov (United States)

    Bond, Andrew R; Hultgårdh-Nilsson, Anna; Knutsson, Anki; Jackson, Christopher L; Rauch, Uwe

    2014-10-01

    To investigate the hypothesis that COMP can influence the morphology, stability and size of murine atherosclerotic lesions. ApoE- and ApoE/COMP-knockout mice were fed a high-fat diet to develop atherosclerotic plaques at lesion sites of three different types; inflammatory and fibrous plaques induced in the carotid artery by low or oscillatory shear stress, respectively, and spontaneously developing plaques in the brachiocephalic artery. The localization of COMP in the plaques and the effect of COMP deficiency on plaque development were evaluated. COMP immunoreactivity was observed in about half of the investigated plaques from the ApoE null mice, mainly located along the intima-medial border. There were no significant differences in the size of inflammatory and fibrous carotid plaques between the genotypes. Plaques in the brachiocephalic artery from ApoE mice lacking COMP were increased in size with 54%. In these plaques the collagen content was also increased by 48%. There were no differences in relative collagen content in inflammatory and fibrous carotid plaques between genotypes. Polarized light microscopy showed that the increase in total collagen in brachiocephalic plaques was more than proportionally accounted for by an increase in thicker collagen fibrils. We have shown that COMP deficiency has a significant impact on atherosclerotic plaque morphology and size. Our data also suggest that an altered collagen metabolism may be an important mechanism in this finding. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Atherosclerotic plaque regression: fact or fiction?

    Science.gov (United States)

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

    2010-08-01

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

  9. Chlamydia pneumoniae and symptomatic carotid atherosclerotic plaque: a prospective study Chlamydia pneumoniae e placa aterosclerótica sintomática de carótida: um estudo prospectivo

    Directory of Open Access Journals (Sweden)

    Rubens J. Gagliardi

    2007-06-01

    Full Text Available OBJECTIVE: To investigate the possible link between symptomatic carotid atherosclerotic plaque and Chlamydia pneumoniae. BACKGROUND: Recently, several studies have demonstrated that there may be a possible link between Chlamydia pneumonia and carotid atherosclerosis, however the real role of Chlamydia pneumoniae is not completely understood. METHOD: This is a prospective study with a total of 52 patients analyzed. All patients had been submitted to endarterectomy, and had suffered thrombotic ischemic stroke or transient ischemic attack up to 60 days prior to the surgery. Every patient presented carotid stenosis over 70%. The plaque was removed during the surgery and the laboratory exams were immediately done. Evaluation of Chlamydia pneumoniae DNA was done using polymerase chain reaction (PCR. RESULTS: The PCR analyses of all 52 patients were negative for Chlamydia pneumoniae. CONCLUSION: These initial results do not show a relationship between Chlamydia pneumoniae and symptomatic carotid atherosclerotic plaque.OBJETIVO: Investigar a possível relação entre placa sintomática de carótidas e Chlamydia pneumoniae. INTRODUÇÃO: Vários estudos têm demonstrado uma possível relação entre Chlamydia pneumonia e aterosclerose carotídea, entretanto o papel definitivo da bactéria não é totalmente conhecido. Há muita especulação: poderia iniciar o processo aterosclerótico, agravá-lo ou desestabilizá-lo. MÉTODO: Estudo prospectivo com um total de 52 pacientes, endarterectomizados e previamente acometidos de acidente vascular cerebral isquêmico ou crise isquêmica transitória, em até 60 dias antes da cirurgia. Todos os pacientes apresentavam estenose carotídea superior a 70%. Os testes laboratoriais foram realizados imediatamente após a endarterectomia. A Chlamydia pneumoniae foi pesquisada através de exame de DNA com reação de polimerização em cadeia (PCR. RESULTADOS: O PCR dos 52 pacientes foram negativos para Chlamydia

  10. Mathematical models for atherosclerotic plaque evolution

    NARCIS (Netherlands)

    Bulelzai, M.A.K.

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  12. Ophthalmic masquerades of the atherosclerotic carotids

    Directory of Open Access Journals (Sweden)

    Anupriya Arthur

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  14. Macrophage antioxidant protection within atherosclerotic plaques.

    Science.gov (United States)

    Gieseg, Steven P; Leake, David S; Flavall, Elizabeth M; Amit, Zunika; Reid, Linzi; Yang, Ya-Ting

    2009-01-01

    Macrophage cells within inflammatory lesions are exposed to a wide range of degrading and cytotoxic molecules including reactive oxygen species. Unlike neutrophils, macrophages do not normally die in this environment but continue to generate oxidants, phagocytose cellular remains, and release a range of cyto-active agents which modulate the immune response. It is this potential of the macrophage cell to survive in an oxidative environment that allows the growth and complexity of advanced atherosclerotic plaques. This review will examine the oxidants encountered by macrophages within an atherosclerotic plaque and describe some of the potential antioxidant mechanisms which enable macrophages to function within inflammatory lesions. Ascorbate, a-tocopherol, and glutathione appear to be central to the protection of macrophages yet additional antioxidant mechanisms appear to be involved. Gamma-Interferon causes macrophages to generate 7,8-dihydroneopterin, neopterin and 3-hydroxyanthranilic acid both of which have antioxidant properties. Manganese superoxide dismutase is also upregulated in macrophages. The evidence that these antioxidants provide further protection, so allowing the macrophage cells to survive within sites of chronic inflammation such as atherosclerotic plaques, will be described.

  15. Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques.

    Science.gov (United States)

    Rutten, Bert; Tersteeg, Claudia; Vrijenhoek, Joyce E P; van Holten, Thijs C; Elsenberg, Ellen H A M; Mak-Nienhuis, Elske M; de Borst, Gert Jan; Jukema, J Wouter; Pijls, Nico H J; Waltenberger, Johannes; van Zonneveld, Anton Jan; Moll, Frans L; McClellan, Elizabeth; Stubbs, Andrew; Pasterkamp, Gerard; Hoefer, Imo; de Groot, Philip G; Roest, Mark

    2014-01-01

    Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques. Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort). We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585-11267) area under the curve (AUC) vs. 9633 (3580-21565) AUC, P<0.001). Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean ± SD; 8969 ± 3485 AUC vs. 7020 ± 3442 AUC, P = 0.02). All associations remained significant after adjustment for age, sex and use of drugs against platelet activation. Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.

  16. Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques.

    Directory of Open Access Journals (Sweden)

    Bert Rutten

    Full Text Available Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs and macrophages in human atherosclerotic carotid plaques.Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP, in two independent cohorts: the Circulating Cells cohort (n = 244 and the Athero-Express cohort (n = 91. Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort. Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort.We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range: 4153 (1585-11267 area under the curve (AUC vs. 9633 (3580-21565 AUC, P<0.001. Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean ± SD; 8969 ± 3485 AUC vs. 7020 ± 3442 AUC, P = 0.02. All associations remained significant after adjustment for age, sex and use of drugs against platelet activation.Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.

  17. Oral glucose tolerance test predicts increased carotid plaque burden in patients with acute coronary syndrome.

    Directory of Open Access Journals (Sweden)

    Thorarinn A Bjarnason

    Full Text Available Type 2 diabetes and prediabetes are established risk factors for atherosclerosis. The aim of this study was to evaluate the atherosclerotic plaque burden in the carotid arteries of patients with acute coronary syndrome according to their glycemic status.Patients with acute coronary syndrome and no previous history of type 2 diabetes were consecutively included in the study. Glucose metabolism was evaluated with fasting glucose in plasma, HbA1c and a standard two-hour oral glucose tolerance test. Atherosclerotic plaque in the carotid arteries was evaluated with a standardized ultrasound examination where total plaque area was measured and patients classified as having no plaque or a significant plaque formation.A total of 245 acute coronary syndrome patients (male 78%, 64 years (SD: 10.9 were included. The proportion diagnosed with normal glucose metabolism, prediabetes and type 2 diabetes was 28.6%, 64.1% and 7.3%, respectively. A significant atherosclerotic plaque was found in 48.5%, 66.9% and 72.2% of patients with normal glucose metabolism, prediabetes and type 2 diabetes, respectively. An incremental increase in total plaque area was found from normal glucose metabolism to prediabetes (25.5% and from normal glucose metabolism to type 2 diabetes (35.9% (p = 0.04. When adjusted for conventional cardiovascular risk factors the OR of having significant atherosclerotic plaque in the carotid arteries was 2.17 (95% CI 1.15-4.15 for patients with newly diagnosed dysglycemia compared to patients with normal glucose metabolism. When additionally adjusted for the 2-hour plasma glucose after glucose loading (2hPG the OR attenuated to 1.77 (95% CI 0.83-3.84.Newly detected dysglycemia is an independent predictor of significant atherosclerotic plaque in the carotid arteries with oral glucose tolerance test as a major determinant of carotid plaque burden in this group of individuals with acute coronary syndrome.

  18. When to image carotid plaque inflammation with FDG PET/CT

    DEFF Research Database (Denmark)

    Græbe, Martin; Borgwardt, Lise; Højgaard, Liselotte

    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...... the contrast between the plaque and blood-pool FDG activity. However, for prospective studies the late acquisition is inconvenient for the patient and staff, and most retrospective studies of plaque uptake use data from early acquisition protocols. The objective was to evaluate changes in the quantification...... methods of FDG uptake in carotid artery plaques between early and late PET scans....

  19. Is Cadmium Exposure Associated with the Burden, Vulnerability and Rupture of Human Atherosclerotic Plaques?

    Science.gov (United States)

    Sallsten, Gerd; Lundh, Thomas; Barregard, Lars

    2015-01-01

    The general population is exposed to cadmium from food and smoking. Cadmium is a widely spread toxic pollutant that seems to be associated with cardiovascular diseases, although little is known if it contributes to the occurrence of atherosclerotic plaques and the process whereby plaques become vulnerable and are prone to rupture. We tested the hypotheses that cadmium exposure is associated not only with an increased subclinical burden of atherosclerotic plaques in different vascular territories and early signs of plaque vulnerability, but also with cadmium content and plaque-rupture in the clinical phase of the disease. Ultrasound technique was used to measure plaque prevalence and echogenicity in the carotid and femoral arteries in a population sample of women (n = 599) in whom blood cadmium was measured. In addition cadmium was measured in snap-frozen endarterectomies and whole blood obtained from patients who were referred to surgery because of symptomatic carotid plaques (n = 37). Sixteen endarterectomies were divided into three parts corresponding to different flow conditions and plaque vulnerability. In the population sample blood cadmium was associated with the number of vascular territories with plaques (p = 0.003 after adjustment for potential confounders). The cadmium concentrations in symptomatic plaques were 50-fold higher in plaque tissue than in blood. Cadmium levels in blood and plaque correlated, also after adjustment for smoking and other cardiovascular risk factors (pcadmium content was double as high in the part where plaque rupture usually occurs. In conclusion, the results show that cadmium exposure is associated with the burden of subclinical atherosclerosis in middle-aged women with different degrees of glucose tolerance, and that the content of cadmium in symptomatic plaques in patients is related to that in blood, but much higher, and preferentially located in the part of plaque where rupture often occurs. PMID:25816093

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

    Directory of Open Access Journals (Sweden)

    Elvira E Ziganshina

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

  1. 3D Isotropic MR Culprit Plaque Visualization of Carotid Plaque Edema and Hemorrhage with Motion Sensitized Blood Suppression

    DEFF Research Database (Denmark)

    Søvsø Szocska Hansen, Esben; Pedersen, Steen Fjord; Bloch, Lars Ø.

    2014-01-01

    Purpose/Introduction Atherosclerotic carotid artery disease is estimated to represent the etiology for one quarter of all strokes. Carotid cardiovascular magnetic resonance (CMR) and magnetic resonance angiography are promising tools in the evaluation of carotid atherosclerosis. Intraplaque...... hemorrhage and plaque edema may represent advanced stages of atherosclerosis[1, 2]. In this study, we present a novel multi-contrast 3D motion sensitized black-blood CMR imaging sequence, which detects both plaque edema and hemorrhage with positive contrast. Subjects and Methods The 3D imaging sequence...... to lumen was 39.74±6.75. Discussion/Conclusion In conclusion, the proposed 3D isotropic multi-contrast CMR technique detects plaque edema and hemorrhage with positive contrast and excellent black-blood contrast, which may facilitate evaluation of carotid atherosclerosis. Ongoing studies will include CMR...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: This study aimed to determine if delayed (18)F-fluorodeoxyglucose ((18)FDG) PET/CT imaging improves quantitation of atherosclerotic plaque inflammation. Blood-pool activity can disturb the arterial (18)FDG signal. With time, blood-pool activity declines. Therefore, delayed imaging can...... potentially improve quantitation of vascular inflammation. METHODS AND RESULTS: 40 subjects were prospectively assessed by dual-time-point PET/CT imaging at approximately 90 and 180 minutes after (18)FDG administration. For both time-points, global uptake of (18)FDG was determined in the carotid arteries...... at 180 minutes significant positive relations were observed between SCORE % and carotid (τ = 0.25, P = .045) and aortic (τ = 0.33, P = .008) cSUVMAX. CONCLUSIONS: Delayed (18)FDG PET/CT imaging at 180 minutes improves quantitation of atherosclerotic plaque inflammation over imaging at 90 minutes...

  3. 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

  4. Atherosclerotic plaque rupture: local or systemic process?

    NARCIS (Netherlands)

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

    2003-01-01

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

  5. 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.

  6. Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration.

    Science.gov (United States)

    Rautou, Pierre-Emmanuel; Leroyer, Aurélie S; Ramkhelawon, Bhama; Devue, Cécile; Duflaut, Dominique; Vion, Anne-Clémence; Nalbone, Gilles; Castier, Yves; Leseche, Guy; Lehoux, Stéphanie; Tedgui, Alain; Boulanger, Chantal M

    2011-02-04

    Membrane-shed submicron microparticles (MPs) released following cell activation or apoptosis accumulate in atherosclerotic plaques, where they stimulate endothelial proliferation and neovessel formation. The aim of the study was to assess whether or not MPs isolated from human atherosclerotic plaques contribute to increased endothelial adhesion molecules expression and monocyte recruitment. Human umbilical vein and coronary artery endothelial cells were exposed to MPs isolated from endarterectomy specimens (n=62) and characterized by externalized phosphatidylserine. Endothelial exposure to plaque, but not circulating, MPs increased ICAM-1 levels in a concentration-dependant manner (3.4-fold increase) without affecting ICAM-1 mRNA levels. Plaque MPs harbored ICAM-1 and transferred this adhesion molecule to endothelial cell membrane in a phosphatidylserine-dependent manner. MP-borne ICAM-1 was functionally integrated into cell membrane as demonstrated by the increased ERK1/2 phosphorylation following ICAM-1 ligation. Plaque MPs stimulated endothelial monocyte adhesion both in culture and in isolated perfused mouse carotid. This effect was also observed under flow condition and was prevented by anti-LFA-1 and anti-ICAM-1 neutralizing antibodies. MPs isolated from symptomatic plaques were more potent in stimulating monocyte adhesion than MPs from asymptomatic patients. Plaque MPs did not affect the release of interleukin-6, interleukin-8, or MCP-1, nor the expression of VCAM-1 and E-selectin. These results demonstrate that MPs isolated from human atherosclerotic plaques transfer ICAM-1 to endothelial cells to recruit inflammatory cells and suggest that plaque MPs promote atherosclerotic plaque progression.

  7. Artery buckling affects the mechanical stress in atherosclerotic plaques.

    Science.gov (United States)

    Sanyal, Arnav; Han, Hai-Chao

    2015-01-01

    Tortuous arteries are often seen in patients with hypertension and atherosclerosis. While the mechanical stress in atherosclerotic plaque under lumen pressure has been studied extensively, the mechanical stability of atherosclerotic arteries and subsequent effect on the plaque stress remain unknown. To this end, we investigated the buckling and post-buckling behavior of model stenotic coronary arteries with symmetric and asymmetric plaque. Buckling analysis for a model coronary artery with symmetric and asymmetric plaque was conducted using finite element analysis based on the dimensions and nonlinear anisotropic materials properties reported in the literature. Artery with asymmetric plaque had lower critical buckling pressure compared to the artery with symmetric plaque and control artery. Buckling increased the peak stress in the plaque and led to the development of a high stress concentration in artery with asymmetric plaque. Stiffer calcified tissue and severe stenosis increased the critical buckling pressure of the artery with asymmetric plaque. Arteries with atherosclerotic plaques are prone to mechanical buckling which leads to a high stress concentration in the plaques that can possibly make the plaques prone to rupture.

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

    Directory of Open Access Journals (Sweden)

    Adrienne Müller

    2014-03-01

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

  9. Characterization of Atherosclerotic Plaques by Laser Speckle Imaging

    Science.gov (United States)

    Nadkarni, Seemantini K.; Bouma, Brett E.; Helg, Tina; Chan, Raymond; Halpern, Elkan; Chau, Alexandra; Minsky, Milan Singh; Motz, Jason T.; Houser, Stuart L.; Tearney, Guillermo J.

    2010-01-01

    Background A method capable of determining atherosclerotic plaque composition and measuring plaque viscoelasticity can provide valuable insight into intrinsic features associated with plaque rupture and can enable the identification of high-risk lesions. In this article, we describe a new optical technique, laser speckle imaging (LSI), that measures an index of plaque viscoelasticity. We evaluate the potential of LSI for characterizing atherosclerotic plaque. Methods and Results Time-varying helium-neon laser speckle images were acquired from 118 aortic plaque specimens from 14 human cadavers under static and deforming conditions (0 to 200 μm/s). Temporal fluctuations in the speckle patterns were quantified by exponential fitting of the normalized cross-correlation of sequential frames in each image series of speckle patterns to obtain the exponential decay time constant, τ. The decorrelation time constants of thin-cap fibroatheromas (TCFA) (τ=47.5±19.2 ms) were significantly lower than those of other atherosclerotic lesions (P90%. Speckle decorrelation time constants demonstrated strong correlation with histological measurements of plaque collagen (R=0.73, P0.05). Conclusions The measurement of speckle decorrelation time constant from laser speckle images provides an index of plaque viscoelasticity and facilitates the characterization of plaque type. Our results demonstrate that LSI is a highly sensitive technique for characterizing plaque and identifying thin-cap fibroatheromas. PMID:16061738

  10. Approach To Unstable Plaque In Carotid Disease

    Directory of Open Access Journals (Sweden)

    Mojdeh Ghabaee

    2017-02-01

    Full Text Available Risk of cerebral infarction due to thrombo emboli originating  from carotid artery disease estimated to be near 15%, and this risk  is closely associated with the severity of luminal stenosis. But at the same time characteristics  of the plaque should be taken into account for therapeutic planning when the patient is asymptomatic and the diameter of the stenosis does not reach the threshold of 70%. Search for markers of plaque vulnerability, instability, or thromboembolic potential as complementary to the degree of the luminal stenosis in stroke risk prediction should be considered .These morphologic features of carotid plaques are increasingly believed to be one of those markers that could carry further prognostic information, and early recognition of these plaques features may identify a high-risk subgroup of patients who might particularly benefit from aggressive interventions with aggressive medical treatment. Color and duplex Doppler sonography  evaluates both  morphologic and hemodynamic   abnormalitie of carotid. Echogensity, degree of stenosis and plaque surface features are essential parameters of morphological abnormality.

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

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  12. Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis

    NARCIS (Netherlands)

    Sluimer, Judith C.; Gasc, Jean-Marie; van Wanroij, Job L.; Kisters, Natasja; Groeneweg, Mathijs; Sollewijn Gelpke, Maarten D.; Cleutjens, Jack P.; van den Akker, Luc H.; Corvol, Pierre; Wouters, Bradly G.; Daemen, Mat J.; Bijnens, Ann-Pascale J.

    2008-01-01

    We sought to examine the presence of hypoxia in human carotid atherosclerosis and its association with hypoxia-inducible transcription factor (HIF) and intraplaque angiogenesis. Atherosclerotic plaques develop intraplaque angiogenesis, which is a typical feature of hypoxic tissue and expression of

  13. 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.

  14. Cap buckling as a potential mechanism of atherosclerotic plaque vulnerability.

    Science.gov (United States)

    Abdelali, Maria; Reiter, Steven; Mongrain, Rosaire; Bertrand, Michel; L'Allier, Philippe L; Kritikou, Ekaterini A; Tardif, Jean-Claude

    2014-04-01

    Plaque rupture in atherosclerosis is the primary cause of potentially deadly coronary events, yet about 40% of ruptures occur away from the plaque cap shoulders and cannot be fully explained with the current biomechanical theories. Here, cap buckling is considered as a potential destabilizing factor which increases the propensity of the atherosclerotic plaque to rupture and which may also explain plaque failure away from the cap shoulders. To investigate this phenomenon, quasistatic 2D finite element simulations are performed, considering the salient geometrical and nonlinear material properties of diverse atherosclerotic plaques over the range of physiological loads. The numerical results indicate that buckling may displace the location of the peak von Mises stresses in the deflected caps. Plaque buckling, together with its deleterious effects is further observed experimentally in plaque caps using a physical model of deformable mock coronary arteries with fibroatheroma. Moreover, an analytical approach combining quasistatic equilibrium equations with the Navier-Bresse formulas is used to demonstrate the buckling potential of a simplified arched slender cap under intraluminal pressure and supported by foundations. This analysis shows that plaque caps - calcified, fibrotic or cellular - may buckle in specific undulated shapes once submitted to critical loads. Finally, a preliminary analysis of intravascular ultrasonography recordings of patients with atherosclerotic coronary arteries corroborates the numerical, experimental and theoretical findings and shows that various plaque caps buckle in vivo. By displacing the sites of high stresses in the plaque cap, buckling may explain the atherosclerotic plaque cap rupture at various locations, including cap shoulders. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  16. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    Directory of Open Access Journals (Sweden)

    Sunny Goel

    2015-01-01

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

  17. Decreased cathepsin K levels in human atherosclerotic plaques are associated with plaque instability.

    Science.gov (United States)

    Zhao, Huiying; Qin, Xiujiao; Wang, Shuai; Sun, Xiwei; Dong, Bin

    2017-10-01

    Investigating the determinants and dynamics of atherosclerotic plaque instability is a key area of current cardiovascular research. Extracellular matrix degradation from excessive proteolysis induced by enzymes such as cathepsin K (Cat K) is implicated in the pathogenesis of unstable plaques. The current study assessed the expression of Cat K in human unstable atherosclerotic plaques. Specimens of popliteal arteries with atherosclerotic plaques were classified as stable (K and cystatin C (Cys C) were assessed by immunohistochemical examination and levels of Cat K mRNA were detected by semi-quantitative reverse transcriptase polymerase chain reaction. Morphological changes including a larger lipid core, endothelial proliferation with foam cells and destruction of internal elastic lamina were observed in unstable atherosclerotic plaques. In unstable plaques, the expression of Cat K protein and mRNA was upregulated, whereas Cys C protein expression was downregulated. The interplay between Cat K and Cys C may underlie the progression of plaques from stable to unstable and the current study indicated that Cat K and Cys C are potential targets for preventing and treating vulnerable atherosclerotic plaque ruptures.

  18. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients.

    Science.gov (United States)

    Tawakol, Ahmed; Migrino, Raymond Q; Bashian, Gregory G; Bedri, Shahinaz; Vermylen, David; Cury, Ricardo C; Yates, Denise; LaMuraglia, Glenn M; Furie, Karen; Houser, Stuart; Gewirtz, Henry; Muller, James E; Brady, Thomas J; Fischman, Alan J

    2006-11-07

    Given the importance of inflammation in atherosclerosis, we sought to determine if atherosclerotic plaque inflammation could be measured noninvasively in humans using positron emission tomography (PET). Earlier PET studies using fluorodeoxyglucose (FDG) demonstrated increased FDG uptake in atherosclerotic plaques. Here we tested the ability of FDG-PET to measure carotid plaque inflammation in patients who subsequently underwent carotid endarterectomy (CEA). Seventeen patients with severe carotid stenoses underwent FDG-PET imaging 3 h after FDG administration (13 to 25 mCi), after which carotid plaque FDG uptake was determined as the ratio of plaque to blood activity (target to background ratio, TBR). Less than 1 month after imaging, subjects underwent CEA, after which carotid specimens were processed to identify macrophages (staining with anti-CD68 antibodies). There was a significant correlation between the PET signal from the carotid plaques and the macrophage staining from the corresponding histologic sections (r = 0.70; p < 0.0001). When mean FDG uptake (mean TBR) was compared with mean inflammation (mean percentage CD68 staining) for each of the 17 patients, the correlation was even stronger (r = 0.85; p < 0.0001). Fluorodeoxyglucose uptake did not correlate with plaque area, plaque thickness, or area of smooth muscle cell staining. We established that FDG-PET imaging can be used to assess the severity of inflammation in carotid plaques in patients. If subsequent natural history studies link increased FDG-PET activity in carotid arteries with clinical events, this noninvasive measure could be used to identify a subset of patients with carotid atherosclerosis in need of intensified medical therapy or carotid artery intervention to prevent stroke.

  19. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    OpenAIRE

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

    2015-01-01

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

  20. Three-dimensional carotid ultrasound plaque texture predicts vascular events

    DEFF Research Database (Denmark)

    van Engelen, Arna; Wannarong, Thapat; Parraga, Grace

    2014-01-01

    BACKGROUND AND PURPOSE: Carotid ultrasound atherosclerosis measurements, including those of the arterial wall and plaque, provide a way to monitor patients at risk of vascular events. Our objective was to examine carotid ultrasound plaque texture measurements and the change in carotid plaque...... texture during 1 year in patients at risk of events and to compare these with measurements of plaque volume and other risk factors as predictors of vascular events. METHODS: We evaluated 298 patients with carotid atherosclerosis using 3-dimensional (3D) ultrasound at baseline and after 1 year and measured...... carotid plaque volume and 376 measures of plaque texture. Patients were followed up to 5 years (median [range], 3.12 [0.77-4.66]) for myocardial infarction, transient ischemic attack, and stroke. Sparse Cox regression was used to select the most predictive plaque texture measurements in independent...

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

    Science.gov (United States)

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

    2016-08-20

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

  2. Ultrasound Vascular Elastography as a Tool for Assessing Atherosclerotic Plaques

    DEFF Research Database (Denmark)

    Mahmood, Badar; Ewertsen, C; Carlsen, Jørn

    2016-01-01

    compared to B-mode ultrasound alone. Most studies reported higher strain values for vulnerable plaques. Ultrasound elastography has potential as a clinical tool in the assessment of atherosclerotic plaques. Elastography is able to distinguish between different plaque types, but there is considerable...... Library and Web of Science databases. A standardized template was used to extract relevant data following the PRISMA 2009 checklist. 20 articles were included in this paper. The studies were heterogeneous. All studies reported that elastography was a feasible technique and provided additional information...

  3. Classification of coronary atherosclerotic plaques ex vivo with T1, T2, and ultrashort echo time CMR.

    Science.gov (United States)

    Károlyi, Mihály; Seifarth, Harald; Liew, Gary; Schlett, Christopher L; Maurovich-Horvat, Pál; Stolzmann, Paul; Dai, Guangping; Huang, Shuning; Goergen, Craig J; Nakano, Masataka; Otsuka, Fumiyuki; Virmani, Renu; Hoffmann, Udo; Sosnovik, David E

    2013-04-01

    This study sought to determine whether the classification of human coronary atherosclerotic plaques with T1, T2, and ultrashort echo time (UTE) cardiac magnetic resonance (CMR) would correlate well with atherosclerotic plaque classification by histology. CMR has been extensively used to classify carotid plaque, but its ability to characterize coronary plaque remains unknown. In addition, the detection of plaque calcification by CMR remains challenging. Here, we used T1, T2, and UTE CMR to evaluate atherosclerotic plaques in fixed post-mortem human coronary arteries. We hypothesized that the combination of T1, T2, and UTE CMR would allow both calcified and lipid-rich coronary plaques to be accurately detected. Twenty-eight plaques from human donor hearts with proven coronary artery disease were imaged at 9.4-T with a T1-weighted 3-dimensional fast low-angle shot (FLASH) sequence (250-μm resolution), a T2-weighted rapid acquisition with refocused echoes (RARE) sequence (in-plane resolution 0.156 mm), and an UTE sequence (300-μm resolution). Plaques showing selective hypointensity on T2-weighted CMR were classified as lipid-rich. Areas of hypointensity on the T1-weighted images, but not the UTE images, were classified as calcified. Hyperintensity on the T1-weighted and UTE images was classified as hemorrhage. Following CMR, histological characterization of the plaques was performed with a pentachrome stain and established American Heart Association criteria. CMR showed high sensitivity and specificity for the detection of calcification (100% and 90%, respectively) and lipid-rich necrotic cores (90% and 75%, respectively). Only 2 lipid-rich foci were missed by CMR, both of which were extremely small. Overall, CMR-based classification of plaque was in complete agreement with the histological classification in 22 of 28 cases (weighted κ = 0.6945, p classification of human coronary atherosclerotic plaque. Copyright © 2013 American College of Cardiology Foundation

  4. 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)

    Müller, Adrienne; Krämer, Stefanie D.; Meletta, Romana; Beck, Katharina; Selivanova, Svetlana V.; Rancic, Zoran; Kaufmann, Philipp A.; Vos, Bernhard; Meding, Jörg; Stellfeld, Timo; Heinrich, Tobias K.; Bauser, Marcus; Hütter, Joachim; Dinkelborg, Ludger M.; Schibli, Roger; Ametamey, Simon M.

    2014-01-01

    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

  5. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

    NARCIS (Netherlands)

    Bot, M.; , van, Berkel T.J.C.

    2013-01-01

    Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by

  6. 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

  7. Humanin, a Cytoprotective Peptide, Is Expressed in Carotid Artherosclerotic Plaques in Humans

    Science.gov (United States)

    Zacharias, David G.; Kim, Sung Gyun; Massat, Alfonso Eirin; Bachar, Adi R.; Oh, Yun K.; Herrmann, Joerg; Rodriguez-Porcel, Martin; Cohen, Pinchas; Lerman, Lilach O.; Lerman, Amir

    2012-01-01

    Objective The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN) is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques. Methods and Results Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13% of plaque area, p<0.0001). These data were further confirmed by immunoblot (density of HN/β-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01). TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46% of nuclei, p<0.01). Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization), smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9. Conclusions The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque. PMID:22328926

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

    International Nuclear Information System (INIS)

    Dimastromatteo, Julien

    2010-01-01

    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. 99m Tc-B2702p, 20 derivatives, 99m Tc-VP and 99m Tc-VINP28 were evaluated in an experimental model of atherosclerosis (ApoE-/- mice with left carotid artery ligation). 99m Tc- 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 99m Tc-RAFT-RGD in the detection of myocardial angiogenesis. 99m Tc-RAFT-RGD allow us to perform noninvasive molecular imaging of myocardial angiogenesis in an experimental model. (author)

  9. Potential benefits of eicosapentaenoic acid on atherosclerotic plaques.

    Science.gov (United States)

    Nelson, J R; Wani, O; May, H T; Budoff, M

    2017-04-01

    Residual cardiovascular (CV) risk remains in some patients despite optimized statin therapy and may necessitate add-on therapy to reduce this risk. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, lowers plasma triglyceride levels without raising low-density lipoprotein cholesterol levels and has potential beneficial effects on atherosclerotic plaques. Animal studies have shown that EPA reduces levels of pro-inflammatory cytokines and chemokines. In clinical trials utilizing a wide spectrum of plaque imaging modalities, EPA has shown beneficial effects on plaque characteristics. Studies of patients with coronary artery disease receiving statin therapy suggest that EPA may decrease plaque vulnerability and prevent plaque progression. EPA also decreased pentraxin-3 and macrophage accumulation. A large, randomized, Japanese study reported that EPA plus a statin resulted in a 19% relative reduction in major coronary events at 5years versus a statin alone in patients with hypercholesterolemia (P=0.011). Icosapent ethyl, a high-purity prescription form of EPA ethyl ester, has been shown to reduce triglyceride levels and markers of atherosclerotic inflammation. Results of an ongoing CV outcomes study will further define the potential clinical benefits of icosapent ethyl in reducing CV risk in high-risk patients receiving statin therapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Laser speckle imaging of atherosclerotic plaques through optical fiber bundles

    Science.gov (United States)

    Nadkarni, Seemantini K.; Bouma, Brett E.; Yelin, Dvir; Gulati, Amneet; Tearney, Guillermo J.

    2009-01-01

    Laser speckle imaging (LSI), a new technique that measures an index of plaque viscoelasticity, has been investigated recently to characterize atherosclerotic plaques. These prior studies demonstrated the diagnostic potential of LSI for detecting high-risk plaques and were conducted ex vivo. To conduct intracoronary LSI in vivo, the laser speckle pattern must be transmitted from the coronary wall to the image detector in the presence of cardiac motion. Small-diameter, flexible optical fiber bundles, similar to those used in coronary angioscopy, may be incorporated into an intravascular catheter for this purpose. A key challenge is that laser speckle is influenced by inter-fiber leakage of light, which may be exacerbated during bundle motion. In this study, we tested the capability of optical fiber bundles to transmit laser speckle patterns obtained from atherosclerotic plaques and evaluated the influence of motion on the diagnostic accuracy of fiber bundle-based LSI. Time-varying helium-neon laser speckle images of aortic plaques were obtained while cyclically moving the flexible length of the bundle to mimic coronary motion. Our results show that leached fiber bundles may reliably transmit laser speckle images in the presence of cardiac motion, providing a viable option to conduct intracoronary LSI. PMID:19021396

  11. 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.

  12. Aspirin inhibits human telomerase activation in unstable carotid plaques

    OpenAIRE

    LI, FANGMING; GUO, YI; JIANG, XIN; ZHONG, JIANXIN; LI, GUANDONG; SUN, SHENGGANG

    2013-01-01

    The activation of telomerase in unstable plaques is an important factor in atherosclerosis, and may be predictive of the risk of cerebrovascular diseases. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activation. The aim of the present study was to investigate whether aspirin inhibits the activation of telomerase and hTERT in unstable carotid plaques. Polymorphonuclear neutrophils (PMNs) derived from carotid plaques were isolated fr...

  13. Dystrophin deficiency reduces atherosclerotic plaque development in ApoE-null mice.

    Science.gov (United States)

    Shami, Annelie; Knutsson, Anki; Dunér, Pontus; Rauch, Uwe; Bengtsson, Eva; Tengryd, Christoffer; Murugesan, Vignesh; Durbeej, Madeleine; Gonçalves, Isabel; Nilsson, Jan; Hultgårdh-Nilsson, Anna

    2015-09-08

    Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy. We have previously shown injury-induced neointima formation of the carotid artery in mice with the mdx mutation (causing dystrophin deficiency) to be increased. To investigate the role of dystrophin in intimal recruitment of smooth muscle cells (SMCs) that maintains plaque stability in atherosclerosis we applied a shear stress-modifying cast around the carotid artery of apolipoprotein E (ApoE)-null mice with and without the mdx mutation. The cast induces formation of atherosclerotic plaques of inflammatory and SMC-rich/fibrous phenotypes in regions of low and oscillatory shear stress, respectively. Unexpectedly, presence of the mdx mutation markedly reduced the development of the inflammatory low shear stress plaques. Further characterization of the low shear stress plaques in ApoE-null mdx mice demonstrated reduced infiltration of CD3(+) T cells, less laminin and a higher SMC content. ApoE-null mdx mice were also found to have a reduced fraction of CD3(+) T cells in the spleen and lower levels of cytokines and monocytes in the circulation. The present study is the first to demonstrate a role for dystrophin in atherosclerosis and unexpectedly shows that this primarily involves immune cells.

  14. Comprehensive and rapid assessment of carotid plaques in acute stroke using a new single sweep method for three-dimensional carotid ultrasound.

    Science.gov (United States)

    Kalashyan, Harapet; Saqqur, Maher; Shuaib, Ashfaq; Romanchuk, Helen; Nanda, Navin C; Becher, Harald

    2013-04-01

    We describe a 68-year-old man with acute stroke in whom the newly developed single sweep method for three-dimensional (3D) carotid ultrasound provided a rapid and comprehensive assessment of atherosclerotic plaque burden in the internal carotid artery. The two-dimensional duplex carotid scan diagnosed 50-69% stenosis, and with the three-dimensional method, the markedly hypoechogenic plaque (total volume 1.42 mL) was shown to occupy 77% of the total arterial volume (1.84 mL), consistent with severe lesion. The ultrasound findings were confirmed by computed tomographic angiography and subsequent carotid endarterectomy. The new single sweep 3D carotid ultrasound has the potential to become a valuable clinical tool in the assessment of stroke patients. © 2013, Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    . CONCLUSION: No early changes in CIMT were detected in patients treated with radioactive iodine for benign thyroid disease. No signs of late effects of radioactive iodine on CIMT or plaque presence were found after 10 years of follow-up. The radiation to the carotid arteries by radioactive iodine therapy...... were adjusted for age, sex, cholesterol, smoking status, known atherosclerotic disease, and body mass index. RESULTS: No changes in CIMT were found in the patients followed prospectively for one year after treatment with radioactive iodine for benign thyroid disease (p = 0.58). In the study on late...... effects, there was no difference in CIMT (p = 0.25) or presence of plaques (p = 0.70) between those treated with radioactive iodine and those treated with surgery (9.8 and 5.6 years since treatment, respectively). Furthermore, the level of thyrotropin (TSH) did not influence these atherosclerosis markers...

  16. The use of plaque score measurements to assess changes in atherosclerotic plaque burden induced by lipid-lowering therapy over time: the METEOR study.

    Science.gov (United States)

    Peters, Sanne A E; Dogan, Soner; Meijer, Rudy; Palmer, Mike K; Grobbee, Diederick E; Crouse, John R; O'Leary, Daniel H; Evans, Gregory W; Raichlen, Joel S; Bots, Michiel L

    2011-01-01

    To evaluate whether plaque scoring measurements are able to track changes in atherosclerotic plaque burden over time and to study whether this is affected by lipid-lowering therapy. Data used were from METEOR (Measuring Effects on Intima-Media Thickness: an Evaluation Of Rosuvastatin), a randomized controlled trial of rosuvastatin 40 mg among 984 low-risk patients with modest carotid intima-media thickening (CIMT). In this analysis, duplicate ultrasound images from 12 carotid sites were collected at the baseline and end of the study from 495 European patients and were evaluated for plaque presence and severity. Plaques were scored from near and far walls of the 12 sites (0= none; 1= minimal; 2= moderate; 3= severe) and plaque scores (PS) were combined into two summary measures for each examination. The MeanMaxPS is the mean over the 12 carotid sites of the maximum score at each site and the MaxMaxPS reflects the most severe lesion at any site. Baseline MeanMaxPS and MaxMaxPS were 0.31 (SD: 0.20) and 1.15 (SD: 0.51), respectively. Changes in MeanMaxPS and MaxMaxPS significantly differed between rosuvastatin and placebo (mean difference: -0.03 [SE: 0.01; p =0.016] and -0.09 [SE: 0.04; p =0.027], respectively). In contrast to rosuvastatin, which demonstrated no change from the baseline, placebo showed significant progression in MeanMaxPS and MaxMaxPS (p =0.002; both). The plaque-scoring method proved capable of assessing the change in atherosclerotic plaque burden over time and proved useful to evaluate lipid-lowering in asymptomatic individuals with a low risk of cardiovascular disease and subclinical atherosclerosis.

  17. Effect of calcification on the mechanical stability of plaque based on a three-dimensional carotid bifurcation model

    Directory of Open Access Journals (Sweden)

    Wong Kelvin KL

    2012-02-01

    Full Text Available 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 the rationale for plaque mechanical examination and the feasibility of our simulation model. Meaningful validation of predictions from modelled atherosclerotic plaque model typically requires examination of bona fide atherosclerotic lesions. To analyze a more accurate plaque rupture, fluid-structure interaction is applied to three-dimensional blood-vessel carotid bifurcation modelling. A patient-specific pressure variation is applied onto the plaque to influence its vulnerability. Results Modelling of the human atherosclerotic artery with varying degrees of lipid core elasticity, fibrous cap thickness and calcification gap, which is defined as the distance between the fibrous cap and calcification agglomerate, form the basis of our rupture analysis. Finite element analysis shows that the calcification gap should be conservatively smaller than its threshold to maintain plaque stability. The results add new mechanistic insights and methodologically sound data to investigate plaque rupture mechanics. Conclusion Structural analysis using a three-dimensional calcified model represents a more realistic simulation of late-stage atherosclerotic plaque. We also demonstrate that increases of calcium content that is coupled with a decrease in lipid core volume can stabilize plaque structurally.

  18. Effect of calcification on the mechanical stability of plaque based on a three-dimensional carotid bifurcation model

    Science.gov (United States)

    2012-01-01

    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 the rationale for plaque mechanical examination and the feasibility of our simulation model. Meaningful validation of predictions from modelled atherosclerotic plaque model typically requires examination of bona fide atherosclerotic lesions. To analyze a more accurate plaque rupture, fluid-structure interaction is applied to three-dimensional blood-vessel carotid bifurcation modelling. A patient-specific pressure variation is applied onto the plaque to influence its vulnerability. Results Modelling of the human atherosclerotic artery with varying degrees of lipid core elasticity, fibrous cap thickness and calcification gap, which is defined as the distance between the fibrous cap and calcification agglomerate, form the basis of our rupture analysis. Finite element analysis shows that the calcification gap should be conservatively smaller than its threshold to maintain plaque stability. The results add new mechanistic insights and methodologically sound data to investigate plaque rupture mechanics. Conclusion Structural analysis using a three-dimensional calcified model represents a more realistic simulation of late-stage atherosclerotic plaque. We also demonstrate that increases of calcium content that is coupled with a decrease in lipid core volume can stabilize plaque structurally. PMID:22336469

  19. 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

    2016-03-04

    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.

  20. Plaque hemorrhage in carotid artery disease: Pathogenesis, clinical and biomechanical considerations

    Science.gov (United States)

    Teng, Zhongzhao; Sadat, Umar; Brown, Adam J.; Gillard, Jonathan H.

    2014-01-01

    Stroke remains the most prevalent disabling illness today, with internal carotid artery luminal stenosis due to atheroma formation responsible for the majority of ischemic cerebrovascular events. Severity of luminal stenosis continues to dictate both patient risk stratification and the likelihood of surgical intervention. But there is growing evidence to suggest that plaque morphology may help improve pre-existing risk stratification criteria. Plaque components such a fibrous tissue, lipid rich necrotic core and calcium have been well investigated but plaque hemorrhage (PH) has been somewhat overlooked. In this review we discuss the pathogenesis of PH, its role in dictating plaque vulnerability, PH imaging techniques, marterial properties of atherosclerotic tissues, in particular, those obtained based on in vivo measurements and effect of PH in modulating local biomechanics. PMID:24485514

  1. Atherosclerotic plaque disruption induced by stress and lipopolysaccharide in apolipoprotein E knockout mice.

    Science.gov (United States)

    Ni, Mei; Wang, Yan; Zhang, Mei; Zhang, Peng Fei; Ding, Shi Fang; Liu, Chun Xi; Liu, Xiao Ling; Zhao, Yu Xia; Zhang, Yun

    2009-05-01

    To establish an animal model with disruptions of atherosclerotic plaques, 96 male apolipoprotein E knockout (apoE(-/-)) mice were randomly divided into stress, lipopolysaccharide (LPS), stress+LPS, and control groups (n = 24 each). All mice were fed a high-fat diet throughout the experiment, and carotid atherosclerotic lesions were induced by placement of a constrictive perivascular collar. Four weeks after surgery, mice in the LPS and stress+LPS groups were intraperitoneally injected with LPS (1 mg/kg twice per week for 8 wk). Eight weeks after surgery, mice in the stress and stress+LPS groups were treated with intermittent physical stress (electric foot shock and noise stimulation) for 4 wk. Morphological analysis revealed a plaque disruption rate of 16.7% in control, 34.8% in LPS, 54.2% in stress, and 60.9% in stress+LPS groups. The disruption rates in stress and stress+LPS groups were both significantly higher than those of controls (P = 0.007 and P = 0.002, respectively). Luminal thrombosis secondary to plaque disruption was observed only in the stress+LPS group. Both stress and LPS stimulation significantly decreased fibrous cap thickness and increased macrophage and lipid contents in plaques. Moreover, the combination of stress and LPS stimulation further lowered cap thickness and enhanced accumulation of macrophages and expression of inflammatory cytokines and matrix metalloproteinases. Stress activated the sympathetic nervous system, as manifested by increased blood pressure and flow velocity. Plasma fibrinogen levels were remarkably elevated in the stress and stress+LPS groups. In conclusion, stress- and LPS-costimulated apoE(-/-) mice provide a useful model for studies of plaque vulnerability and interventions.

  2. Analysis of haemodynamic disturbance in the atherosclerotic carotid artery using computational fluid dynamics

    International Nuclear Information System (INIS)

    Birchall, Daniel; Zaman, Azfar; Hacker, Jacob; Davies, Gavin; Mendelow, David

    2006-01-01

    Computational fluid dynamics (CFD) provides a means for the quantitative analysis of haemodynamic disturbances in vivo, but most work has used phantoms or idealised geometry. Our purpose was to use CFD to analyse flow in carotid atherosclerosis using patient-specific geometry and flow data. Eight atherosclerotic carotid arteries and one healthy control artery were imaged with magnetic resonance angiography (MRA) and duplex ultrasound, and the data used to construct patient-specific computational models used for CFD and wall shear stress (WSS) analysis. There is a progressive change in three-dimensional (3-D) velocity profile and WSS profile with increasing severity of stenosis, characterised by increasing restriction of areas of low WSS, change in oscillation patterns, and progressive rise in WSS within stenoses and downstream jets. Areas of turbulent, retrograde flow and of low WSS are demonstrated in the lee of the stenoses. This study presents the largest CFD analysis of abnormal haemodynamics at the atheromatous carotid bifurcation using patient-specific data and provides the basis for further investigation of causal links between haemodynamic variables and atherogenesis and formation of unstable plaque. We propose that this provides a means for the prospective assessment of relative stroke risk in patients with carotid atherosclerosis. (orig.)

  3. Analysis of haemodynamic disturbance in the atherosclerotic carotid artery using computational fluid dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Birchall, Daniel [Newcastle General Hospital, Division of Neuroradiology, Regional Neurosciences Centre, Newcastle-upon-Tyne (United Kingdom); Zaman, Azfar [Regional Cardiothoracic Centre, Division of Cardiology, Newcastle-upon-Tyne (United Kingdom); Hacker, Jacob; Davies, Gavin [Arup Research and Development, London (United Kingdom); Mendelow, David [Regional Neurosciences Centre, Divisions of Neurosurgery, Newcastle-upon-Tyne (United Kingdom)

    2006-05-15

    Computational fluid dynamics (CFD) provides a means for the quantitative analysis of haemodynamic disturbances in vivo, but most work has used phantoms or idealised geometry. Our purpose was to use CFD to analyse flow in carotid atherosclerosis using patient-specific geometry and flow data. Eight atherosclerotic carotid arteries and one healthy control artery were imaged with magnetic resonance angiography (MRA) and duplex ultrasound, and the data used to construct patient-specific computational models used for CFD and wall shear stress (WSS) analysis. There is a progressive change in three-dimensional (3-D) velocity profile and WSS profile with increasing severity of stenosis, characterised by increasing restriction of areas of low WSS, change in oscillation patterns, and progressive rise in WSS within stenoses and downstream jets. Areas of turbulent, retrograde flow and of low WSS are demonstrated in the lee of the stenoses. This study presents the largest CFD analysis of abnormal haemodynamics at the atheromatous carotid bifurcation using patient-specific data and provides the basis for further investigation of causal links between haemodynamic variables and atherogenesis and formation of unstable plaque. We propose that this provides a means for the prospective assessment of relative stroke risk in patients with carotid atherosclerosis. (orig.)

  4. Carotid plaque burden as a measure of subclinical atherosclerosis

    DEFF Research Database (Denmark)

    Sillesen, Henrik; Muntendam, Pieter; Adourian, Aram

    2012-01-01

    The purpose of this study was to compare carotid plaque burden, carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and abdominal aortic diameter (AAD) to coronary artery calcium score (CACS) in people without known cardiovascular disease....

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

    International Nuclear Information System (INIS)

    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

    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. A computational evaluation of sedentary lifestyle effects on carotid hemodynamics and atherosclerotic events incidence.

    Science.gov (United States)

    Caruso, Maria Vittoria; Serra, Raffaele; Perri, Paolo; Buffone, Gianluca; Caliò, Francesco Giuseppe; DE Franciscis, Stefano; Fragomeni, Fragomeni

    2017-01-01

    Hemodynamics has a key role in atheropathogenesis. Indeed, atherosclerotic phenomena occur in vessels characterized by complex geometry and flow pattern, like the carotid bifurcation. Moreover, lifestyle is a significant risk factor. The aim of this study is to evaluate the hemodynamic effects due to two sedentary lifestyles - sitting and standing positions - in the carotid bifurcation in order to identify the worst condition and to investigate the atherosclerosis incidence. The computational fluid dynamics (CFD) was chosen to carry out the analysis, in which in vivo non-invasive measurements were used as boundary conditions. Furthermore, to compare the two conditions, one patient-specific 3D model of a carotid bifurcation was reconstructed starting from computer tomography. Different mechanical indicators, correlated with atherosclerosis incidence, were calculated in addition to flow pattern and pressure distribution: the time average wall shear stress (TAWSS), the oscillatory shear index (OSI) and the relative residence time (RRT). The results showed that the bulb and the external carotid artery emergence are the most probable regions in which atherosclerotic events could happen. Indeed, low velocity and WSS values, high OSI and, as a consequence, areas with chaotic-swirling flow, with stasis (high RRT), occur. Moreover, the sitting position is the worst condition: considering a cardiac cycle, TAWSS is less than 17.2% and OSI and RRT are greater than 17.5% and 21.2%, respectively. This study suggests that if a person spends much time in the sitting position, a high risk of plaque formation and, consequently, of stenosis could happen.

  7. Quantitative assessment of changes in carotid plaques during cilostazol administration using three-dimensional ultrasonography and non-gated magnetic resonance plaque imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Mao; Ohba, Hideki; Mori, Kiyofumi; Narumi, Shinsuke; Katsura, Noriyuki; Ohura, Kazumasa; Terayama, Yasuo [Iwate Medical University, Department of Neurology and Gerontology, Morioka (Japan); Sasaki, Makoto; Kudo, Kohsuke [Iwate Medical University, Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Morioka (Japan)

    2012-09-15

    Cilostazol, an antiplatelet agent, is reported to induce the regression of atherosclerotic changes. However, its effects on carotid plaques are unknown. Hence, we quantitatively investigated the changes that occur within carotid plaques during cilostazol administration using three-dimensional (3D) ultrasonography (US) and non-gated magnetic resonance (MR) plaque imaging. We prospectively examined 16 consecutive patients with carotid stenosis. 3D-US and T1-weighted MR plaque imaging were performed at baseline and 6 months after initiating cilostazol therapy (200 mg/day). We measured the volume and grayscale median (GSM) of the plaques from 3D-US data. We also calculated the contrast ratio (CR) of the carotid plaque against the adjacent muscle and areas of the intraplaque components: fibrous tissue, lipid, and hemorrhage components. The plaque volume on US decreased significantly (median at baseline and 6 months, 0.23 and 0.21 cm{sup 3}, respectively; p = 0.03). In the group exhibiting a plaque volume reduction of more than 10%, GSM on US increased significantly (24.8 and 71.5, respectively; p = 0.04) and CR on MRI decreased significantly (1.13 and 1.04, respectively; p = 0.02). In this group, in addition, the percent area of the fibrous component on MRI increased significantly (68.6% and 79.4%, respectively; p = 0.02), while those of the lipid and hemorrhagic components decreased (24.9% and 20.5%, respectively; p = 0.12) (1.0% and 0.0%, respectively; p = 0.04). There were no substantial changes in intraplaque characteristics in either US or MRI in the other group. 3D-US and MR plaque imaging can quantitatively detect changes in the size and composition of carotid plaques during cilostazol therapy. (orig.)

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  9. Eosinophil Cationic Protein, Carotid Plaque, and Incidence of Stroke.

    Science.gov (United States)

    Sundström, Johannes; Söderholm, Martin; Borné, Yan; Nilsson, Jan; Persson, Margaretha; Östling, Gerd; Melander, Olle; Orho-Melander, Marju; Engström, Gunnar

    2017-10-01

    ECP (eosinophil cationic protein) is a marker of eosinophil activity and degranulation, which has been linked to atherosclerosis and cardiovascular disease. We examined the relationship between ECP, carotid plaque, and incidence of stroke in a prospective population-based cohort. The subjects participated in the Malmö Diet and Cancer Study between 1991 and 1994. A total of 4706 subjects with no history of stroke were included (40% men; mean age, 57.5 years). Carotid plaque was determined by B-mode ultrasound of the right carotid artery. Incidence of stroke was followed up during a mean period of 16.5 years in relation to plasma ECP levels. Subjects in the third tertile (versus first tertile) of ECP tended to have higher prevalence of carotid plaque (odds ratio: 1.18; 95% confidence interval: 1.003-1.39; P =0.044 after multivariate adjustments). A total of 258 subjects were diagnosed with ischemic stroke (IS) during follow-up. ECP was associated with increased incidence of IS after risk factor adjustment (hazard ratio, 1.57; 95% confidence interval: 1.13-2.18; for third versus first tertile; P =0.007). High ECP was associated with increased risk of IS in subjects with carotid plaque. The risk factor-adjusted hazard ratio for IS was 1.86 (95% confidence interval: 1.32-2.63) in subjects with carotid plaque and ECP in the top tertile, compared with those without plaque and ECP in the first or second tertiles. High ECP is associated with increased incidence of IS. The association between ECP and IS was also present in the subgroup with carotid plaque. © 2017 American Heart Association, Inc.

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

    Science.gov (United States)

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

    2017-04-01

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

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

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

    This Ph.D. project was carried out as an industrial research Ph.D. project at B-K Medical and the Department of Information Technology, Technical University of Denmark (DTU), and has focused on medical diagnostic ultrasound investigation of atherosclerotic disease in the carotid arteries. Two major...... inhomogeneities etc. can not directly be incorporated in the modeling. Results obtained using the DRIM have been compared to results from other simulation techniques wherever possible and agreement was found to be high. Further, DRIM results have been compared to experimental results obtained using cylindrical...... 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...

  12. [The progress of nuclear medicine and magnetic resonance molecular imaging of atherosclerotic vulnerable plaques].

    Science.gov (United States)

    Zhao, Zhen-Mei; Qin, Shu-Cun

    2011-04-01

    The major goal of atherosclerotic molecular imaging is to target specific plaque-associated molecules with molecular probe that provide sensitive and specific imaging contrast and acquire molecular imaging. This method will greatly improve detection and characterization of atherosclerotic lesions, especially plaque components. The plaque components are highly associated with plaque rupture and vulnerability to rupture as well as the consequences followed plaque rupture. Thus, the knowledge about plaque composition will have tremendous clinical utility in terms of the treatment and prognosis judgment of patients with atherosclerosis.

  13. Carotid plaque in Alzheimer caregivers and the role of sympathoadrenal arousal.

    Science.gov (United States)

    Roepke, Susan K; Chattillion, Elizabeth A; von Känel, Roland; Allison, Matthew; Ziegler, Michael G; Dimsdale, Joel E; Mills, Paul J; Patterson, Thomas L; Ancoli-Israel, Sonia; Calleran, Susan; Harmell, Alexandrea L; Grant, Igor

    2011-01-01

    To test the hypothesis that those who provide care for a spouse diagnosed with Alzheimer's disease would have increased prevalence of carotid artery plaque compared with noncaregiving controls and that prolonged sympathoadrenal arousal to acute stress would relate to this difference. Providing care for a spouse with Alzheimer's disease has been associated with an increased risk of coronary heart disease, potentially due to the impact of caregiving stress on the atherosclerotic disease process. Participants were 111 spousal caregivers (74 ± 8 years of age; 69% women) to patients with Alzheimer's disease and 51 noncaregiving controls (75 ± 6 years of age; 69% women). Inhome assessment of carotid artery plaque via B-mode ultrasonography was conducted. Plasma catecholamine response to an acute speech stressor task was also measured. Logistic regression indicated that caregiving status (i.e., caregiver versus noncaregiver) was associated significantly with a 2.2 times greater odds for the presence of plaque independent of other risk factors of atherosclerosis (95% confidence interval, 1.01-4.73, p = .048). Decreased recovery to basal levels of epinephrine after a psychological stress task was associated significantly with the presence of plaque in caregivers, but not in noncaregivers. Norepinephrine recovery post stressor was not associated with plaque in either group. Caregivers had a higher frequency of carotid plaque compared with noncaregivers. Poorer epinephrine recovery after acute stress was associated with the presence of plaque in caregivers but not in noncaregivers. A prolonged sympathoadrenal response to acute stress might enhance the development of atherosclerosis in chronically stressed Alzheimer caregivers.

  14. Single sweep three-dimensional carotid ultrasound: reproducibility in plaque and artery volume measurements.

    Science.gov (United States)

    Kalashyan, Hayrapet; Shuaib, Ashfaq; Gibson, Patrick H; Romanchuk, Helen; Saqqur, Maher; Khan, Khurshid; Osborne, Jonathon; Becher, Harald

    2014-02-01

    There is a need for non-invasive and accurate techniques for assessment of severity of atherosclerotic disease in the carotid arteries. Recently an automated single sweep three-dimensional ultrasound (3D US) technique became available. The aims of this study were to evaluate the feasibility and reproducibility of the automated single sweep method in a cohort of patients undergoing clinically indicated carotid ultrasound. Consecutive patients with a history of stroke or transient ischemic attack (TIA) and having a plaque in the internal carotid artery (ICA) were recruited for this study. Imaging was performed using a Philips iU 22 ultrasound system equipped with the single sweep volumetric transducer vL 13-5. Analysis was performed offline with software provided by the manufacturer. Two independent observers performed all measurements. Of 137 arteries studied (from 79 patients), plaque and artery volumes could be measured in 106 (77%). Reproducibility of plaque volume measurements was assessed in 82 arteries. Bland-Altman analysis demonstrated good inter-observer reproducibility with limits of agreement -0.06 to +0.07 ml. The mean percentage difference between two observers was 5.6% ± 6.0%. Reproducibility of artery volume measurement was assessed in 31 cases. Bland-Altman analysis demonstrated limits of agreement from -0.15 to +0.15 ml. The mean percentage difference was 6.4 ± 5.9%. The new automated single sweep 3D ultrasound is feasible in the majority of patients. Good reproducibility in plaque and artery volume measurements makes this technique suitable for serial assessment of carotid plaques. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Identification of Ultrasonic Echolucent Carotid Plaques Using Discrete Fréchet Distance Between Bimodal Gamma Distributions.

    Science.gov (United States)

    Huang, Xiaowei; Zhang, Yanling; Meng, Long; Qian, Ming; Wong, Kelvin; Abbott, Derek; Zheng, Rongqin; Zheng, Hairong; Niu, Lili

    2017-03-01

    Echolucent carotid plaques are associated with acute cardiovascular and cerebrovascular events (ACCEs) in atherosclerotic patients. The aim of this study was to develop a computer-aided method for identifying echolucent plaques. A total of 315 ultrasound images of carotid plaques (105 echo-rich, 105 intermediate and 105 echolucent) collected from 153 patients were included in this study. A bimodal gamma distribution was proposed to model the pixel statistics in the gray scale images of plaques. The discrete Fréchet distance features (DFDFs) of each plaque were extracted based on the statistical model. The most discriminative features (MDFs) were obtained from DFDFs by linear discriminant analysis, and a k-nearestneighbor classifier was implemented for classification of different types of plaques. The classification accuracy of the three types of plaques using MDFs can reach 77.46%. When a receiver operating characteristics (ROC) curve was produced to identify echolucent plaques, the area under the curve was 0.831. Our results indicate potential feasibility of the method for identifying echolucent plaques based on DFDFs. Our method may potentially improve the ability of noninvasive ultrasonic examination in risk prediction of ACCEs for patients with plaques.

  16. Plaque Characteristics of Patients with Symptomatic Mild Carotid Artery Stenosis.

    Science.gov (United States)

    Takai, Hiroki; Uemura, Juniti; Yagita, Yoshiki; Ogawa, Yukari; Kinoshita, Keita; Hirai, Satoshi; Ishihara, Manabu; Hara, Keijirou; Toi, Hiroyuki; Matsubara, Shunji; Nishimura, Hirotake; Uno, Masaaki

    2018-03-20

    Carotid revascularization may be considered for severe stenosis, but its use for symptomatic mild stenosis (<50%) with vulnerable plaque or ulcer remains uncertain. The characteristics of patients with symptomatic mild stenosis who underwent revascularization are reviewed. The subjects of this study were 18 patients with symptomatic mild stenosis (<50%) on angiography from among 175 patients who underwent revascularization in our department. The plaques were evaluated by black-blood magnetic resonance imaging (BB-MRI) and ultrasonography (US) and classified into 2 types: type 1 (n = 15), a lesion with an ulcer or mobile plaque or thrombosis on angiography or US; and type 2 (n = 3), a lesion without any of the above. Fourteen patients underwent carotid endarterectomy (CEA), and 4 patients underwent carotid artery stenting. The stenosis on angiography was 27.2% ± 10.7 (5%-41%), and the area carotid artery stenosis rate on US was 69.8 ± 14.5% (44.5%-97%). The stenosis rate of these 2 methods was not at all correlated. In type 1 plaque that underwent CEA, 10 of 11 patients had vulnerable plaque by histopathology, and 1 patient had thrombus on the plaque by operative findings. In type 2 plaque that underwent CEA, all patients had vulnerable plaque by histopathology. During the follow-up period, none of the patients had restenosis or stroke. The findings of US and BB-MRI in patients with symptomatic mild stenosis (<50%) on angiography are important for determining treatment. If BB-MRI or US shows the findings of vulnerable plaque in mild stenosis, surgical treatment may be considered for these patients. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  17. Relationship between Calcification and Vulnerability of the Carotid Plaques.

    Science.gov (United States)

    Pini, Rodolfo; Faggioli, Gianluca; Fittipaldi, Silvia; Vasuri, Francesco; Longhi, Matteo; Gallitto, Enrico; Pasquinelli, Gianandrea; Gargiulo, Mauro; Stella, Andrea

    2017-10-01

    Carotid plaques with a high degree of calcification are usually considered at low embolic risk. However, since a precise evaluation of the extent of calcification is not possible preoperatively through duplex ultrasound and postoperatively by conventional histological examination due to the decalcification process, the relationship between the amount of calcium involvement and plaque vulnerability has not been evaluated yet. This study aims to correlate the extent of carotid plaque calcification with clinical, radiological, and histological complications. Symptomatic and asymptomatic consecutive patients submitted to carotid endarterectomy between January to December 2014 were included in the study. The amount of carotid calcification was assessed at preoperative computed tomography (CT) through measurement of thickness and circumferential calcium extension and graded from 1 to 8 accordingly (Babiarz classification). Patients were then categorized into 2 groups (low-level group: grade 1-5; high-level group: grade 6-8) and correlated with clinical characteristics and ipsilateral cerebral ischemic lesions at CT. Vulnerability of the plaque was assessed histologically according with American Heart Association (AHA) Classification. Results were overall blindly correlated. One hundred five patients (81% male; age: 73 ± 8 years) were enrolled in the study. Forty (38%) were symptomatic and 43 (40%) had an ipsilateral focal lesion at preoperative cerebral CT. Thirty-six (38%) patients had high-level carotid calcification degree at CT scan. At histological analysis, 56 (56%) plaques were considered complicated (AHA type VI). Patients with high-level and low-level carotid calcification had similar epidemiological risk factors, preoperative neurological symptoms, and histological complications (17% vs. 15%, P = 0.76 and 50% vs. 55%, P = 0.62, respectively). The high-level calcification group showed a significantly higher incidence of ipsilateral cerebral lesions at

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-01-15

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

  19. In vivo detection of activated platelets allows characterizing rupture of atherosclerotic plaques with molecular magnetic resonance imaging in mice.

    Directory of Open Access Journals (Sweden)

    Dominik von Elverfeldt

    Full Text Available BACKGROUND: Early and non-invasive detection of platelets on micro atherothrombosis provides a means to identify unstable plaque and thereby allowing prophylactic treatment towards prevention of stroke or myocardial infarction. Molecular magnetic resonance imaging (mMRI of activated platelets as early markers of plaque rupture using targeted contrast agents is a promising strategy. In this study, we aim to specifically image activated platelets in murine atherothrombosis by in vivo mMRI, using a dedicated animal model of plaque rupture. METHODS: An antibody targeting ligand-induced binding sites (LIBS on the glycoprotein IIb/IIIa-receptor of activated platelets was conjugated to microparticles of iron oxide (MPIO to form the LIBS-MPIO contrast agent causing a signal-extinction in T2*-weighted MRI. ApoE(-/- mice (60 weeks-old were fed a high fat diet for 5 weeks. Using a small needle, the surface of their carotid plaques was scratched under blood flow to induce atherothrombosis. In vivo 9.4 Tesla MRI was performed before and repetitively after intravenous injection of either LIBS-MPIO versus non-targeted-MPIO. RESULTS: LIBS-MPIO injected animals showed a significant signal extinction (p<0.05 in MRI, corresponding to the site of plaque rupture and atherothrombosis in histology. The signal attenuation was effective for atherothrombosis occupying ≥ 2% of the vascular lumen. Histology further confirmed significant binding of LIBS-MPIO compared to control-MPIO on the thrombus developing on the surface of ruptured plaques (p<0.01. CONCLUSION: in vivo mMRI detected activated platelets on mechanically ruptured atherosclerotic plaques in ApoE(-/- mice with a high sensititvity. This imaging technology represents a unique opportunity for noninvasive detection of atherothrombosis and the identification of unstable atherosclerotic plaques with the ultimate promise to prevent strokes and myocardial infarctions.

  20. Alternative Splicing of FOXP3 Controls Regulatory T Cell Effector Functions and Is Associated with Human Atherosclerotic Plaque Stability.

    Science.gov (United States)

    Joly, Anne-Laure; Seitz, Christina; Liu, Sang; Kouznetsov, Nikolai V; Gertow, Karl; Westerberg, Lisa S; Paulsson-Berne, Gabrielle; Hansson, Göran K; Andersson, John

    2018-04-04

    Rationale: Regulatory T (Treg) cells suppress immune responses and have been shown to attenuate atherosclerosis. The Treg cell lineage specification factor FOXP3 is essential for Treg cells' ability to uphold immunological tolerance. In humans, FOXP3 exists in several different isoforms, however, their specific role is poorly understood. Objective: To define the regulation and functions of the two major FOXP3 isoforms, FOXP3fl and FOXP3Δ2, as well as to establish whether their expression is associated with ischemic atherosclerotic disease. Methods and Results: Human primary T-cells were transduced with lentiviruses encoding distinct FOXP3 isoforms. The phenotype and function of these cells were analyzed by flow cytometry, in vitro suppression assays and RNA-sequencing. We also assessed the effect of activation on Treg cells isolated from healthy volunteers. Treg cell activation resulted in increased FOXP3 expression that predominantly was made up of FOXP3Δ2. FOXP3Δ2 induced specific transcription of GARP, which functions by tethering the immunosuppressive cytokine TGF-β to the cell membrane of activated Treg cells. RT-PCR was used to determine the impact of alternative splicing of FOXP3 in relation with atherosclerotic plaque stability in a cohort of over 150 patients that underwent carotid endarterectomy. Plaque instability was associated with a lower FOXP3Δ2 transcript usage, when comparing plaques from patients without symptoms and patients with occurrence of recent (<1 month) vascular symptoms including minor stoke, transient ischemic attack or amaurosis fugax. No difference was detected in total levels of FOXP3 mRNA between these two groups. Conclusions: These results suggest that activated Treg cells suppress the atherosclerotic disease process and that FOXP3Δ2 controls a transcriptional program that acts protectively in human atherosclerotic plaques.

  1. Reproducibility of Two 3-D Ultrasound Carotid Plaque Quantification Methods

    DEFF Research Database (Denmark)

    Graebe, Martin; Entrekin, Robert; Collet-Billon, Antoine

    2014-01-01

    Compared with single 2-D images, emerging 3-D ultrasound technologies hold the promise of reducing variability and increasing sensitivity in the quantification of carotid plaques for individual cardiovascular risk stratification. Inter- and intra-observer agreement between a manual, cross-section...

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

    International Nuclear Information System (INIS)

    Kim, Eun Young; Kang, Doo Kyoung; Sun, Joo Sung; Choi, So Yeon

    2013-01-01

    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 3 , 90.4%) than in calcified plaque (median, 0.7 mm 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.

  3. 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.

  4. Multiple pathway assessment to predict anti-atherogenic efficacy of drugs targeting macrophages in atherosclerotic plaques

    NARCIS (Netherlands)

    Alaarg, Amr Muhmed Sabry Abdelhakeem; Zheng, K.H.; van der Valk, F.M.; Eduardo Da Silva, Acarilia; Versloot, M.; Quarles van Ufford, Linda C.; Schulte, D.M.; Storm, Gerrit; Metselaar, Josbert Maarten; Stroes, E.S.; Hamers, A.A.J.

    2016-01-01

    Background Macrophages play a central role in atherosclerosis development and progression, hence, targeting macrophage activity is considered an attractive therapeutic. Recently, we documented nanomedicinal delivery of the anti-inflammatory compound prednisolone to atherosclerotic plaque macrophages

  5. Association between Snoring and High-Risk Carotid Plaque Features.

    Science.gov (United States)

    Kirkham, Erin M; Hatsukami, Thomas S; Heckbert, Susan R; Sun, Jie; Canton, Gador; Yuan, Chun; Weaver, Edward M

    2017-08-01

    Objectives Previous studies have demonstrated an association between snoring and carotid disease independent of sleep apnea. The aim of this study was to quantify the association between self-reported snoring and high-risk carotid plaque features on magnetic resonance imaging (MRI) that predict stroke. Study Design Cross-sectional. Setting Tertiary care university hospital and affiliated county hospital. Methods We surveyed 133 subjects with asymptomatic carotid artery disease that had been previously evaluated with high-resolution MRI. The survey captured data on self-reported snoring (exposure) and covariates (age, sex, body mass index, and sleep apnea via the STOP-Bang questionnaire). A subset of patients underwent home sleep apnea testing. High-risk carotid plaque features were identified on the high-resolution MRI and included thin/ruptured fibrous cap and intraplaque hemorrhage (outcomes). We quantified the association between snoring and high-risk carotid plaque features with the chi-square test (unadjusted analysis) and multivariate logistic regression adjusting for the covariates. Results Of 133 subjects surveyed, 61 (46%) responded; 32 (52%) reported snoring. Significantly higher proportions of snorers than nonsnorers had a thin/ruptured fibrous cap (56% vs 25%, P = .01) and intraplaque hemorrhage (63% vs 29%, P snoring was associated with thin/ruptured fibrous cap (odds ratio, 4.4; 95% CI, 1.1-16.6; P = .04) and intraplaque hemorrhage (odds ratio, 8.2; 95% CI, 2.1-31.6; P snoring and high-risk carotid plaque features on MRI. Further study is warranted to confirm these results in a larger cohort of subjects.

  6. Reconfiguration of NKT Cell Subset Compartment Is Associated with Plaque Development in Patients with Carotid Artery Stenosis.

    Science.gov (United States)

    Cai, Lun; Yu, Lei; Liu, Sa; Li, Tongxun; Zhang, Xiaoping; Cui, Wei; Du, Jie; Zhang, Qinyi

    2017-02-01

    Accumulating evidence shows that immune cells play an important role in carotid atherosclerotic plaque development. In this study, we assessed the association of 6 different natural killer T (NKT) cell subsets, based on CD57 and CD8 expression, with risk for development of carotid atherosclerotic plaque (CAP). Molecular expression by peripheral NKT cells was evaluated in 13 patients with high-risk CAP and control without carotid stenosis (n = 18). High-risk CAP patients, compared with healthy subjects, had less percentage of CD57+CD8- NKT cell subsets (8.64 ± 10.15 versus 19.62 ± 10.8 %; P = 0.01) and CD57+CD8int NKT cell subsets (4.32 ± 3.04 versus 11.87 ± 8.56 %; P = 0.002), with a corresponding increase in the CD57-CD8high NKT cell subsets (33.22 ± 11.87 versus 18.66 ± 13.68 %; P = 0.007). Intracellular cytokine staining showed that CD8+ NKT cell subset was the main cytokine-producing NKT cell. Cytokine production in plasma was measured with Bio-Plex assay. The expression levels of pro-inflammatory mediators (IFN-γ, IL-17, IP-10) were significantly higher in CAP patients as compared to that from controls. These data provide evidence that NKT cell subset compartment reconfiguration in patients with carotid stenosis seems to be associated with the occurrence of carotid atherosclerotic plaque and suggest that both pathogenic and protective NKT cell subsets exist.

  7. Evaluation of collagen in atherosclerotic plaques: the use of two coherent laser-based imaging methods

    Science.gov (United States)

    Nadkarni, Seemantini K.; Bouma, Brett E.; de Boer, Johannes; Tearney, Guillermo J.

    2009-01-01

    Acute coronary events such as myocardial infarction are frequently caused by the rupture of unstable atherosclerotic plaque. Collagen plays a key role in determining plaque stability. Methods to measure plaque collagen content are invaluable in detecting unstable atherosclerotic plaques. Recently, novel coherent laser-based imaging techniques, such as polarization-sensitive optical coherence tomography (PSOCT) and laser speckle imaging (LSI) have been investigated, and they provide a wealth of information related to collagen content and plaque stability. Additionally, given their potential for intravascular use, these technologies will be invaluable for improving our understanding of the natural history of plaque development and rupture and, hence, enable the detection of unstable plaques. In this article we review recent developments in these techniques and potential challenges in translating these methods into intra-arterial use in patients. PMID:18386093

  8. 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)

    Hyafil, Fabien; Schindler, Andreas; Obenhuber, Tilman; Saam, Tobias; Sepp, Dominik; Hoehn, Sabine; Poppert, Holger; Bayer-Karpinska, Anna; Boeckh-Behrens, Tobias; Hacker, Marcus; Nekolla, Stephan G.; Rominger, Axel; Dichgans, Martin; Schwaiger, Markus

    2016-01-01

    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 18 F-fluoro-deoxyglucose positron emission tomography ( 18 F-FDG PET) imaging. Carotid arteries were imaged 150 min after injection of 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. 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 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 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 18 F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral to the stroke, suggesting a causal

  9. 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

  10. Relationship between plasma antioxidant concentrations and carotid intima-media thickness: the Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study.

    Science.gov (United States)

    Riccioni, Graziano; D'Orazio, Nicolantonio; Palumbo, Nicola; Bucciarelli, Valentina; Ilio, Emanuela di; Bazzano, Lydia A; Bucciarelli, Tonino

    2009-06-01

    Few studies have examined the relationship among carotid atherosclerosis, vascular risk factors, and antioxidant plasma concentrations, and those that have reported conflicting results. The aim of this study was to assess the relationship between asymptomatic carotid atherosclerosis, as defined by carotid intima-media thickness (CIMT), and inflammatory markers, plasma lipids and serum antioxidant vitamins. We examined baseline characteristics of the 640 participants in the Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study. All participants were asymptomatic with respect to carotid artery disease in 2006-2007 and underwent physical examination with carotid ultrasound investigation, the collection of medical history and laboratory data. Analysis of variance methods were used to examine differences between participants by category of CIMT. Of the 640 participants, 291 did not have evidence of carotid atherosclerosis (CIMT1.2 mm). Among participants with CIMT> or =0.8 mm, body mass index, blood pressures, total cholesterol, LDL cholesterol, triglycerides, uric acid, C-reactive protein, and fibrinogen were significantly higher, whereas concentrations of vitamin A, vitamin E, lycopene, and beta-carotene were all significantly lower when compared with participants who did not show evidence of carotid atherosclerosis (P<0.001). The optimal control of hypertension, diabetes, and dyslipidemia, in addition to smoking cessation and an adequate intake of antioxidant micronutrients from foods represent a key for the prevention of atherosclerotic disease.

  11. Effects of exercise training on carotid intima-media thickness in patients with type 2 diabetes and coronary artery disease. Influence of carotid plaques.

    Science.gov (United States)

    Byrkjeland, Rune; Stensæth, Knut-Haakon; Anderssen, Sigmund; Njerve, Ida U; Arnesen, Harald; Seljeflot, Ingebjørg; Solheim, Svein

    2016-01-22

    Carotid intima-media thickness (cIMT) holds prognostic information for future cardiovascular disease and is associated with the extent of coronary atherosclerosis. We investigated the effect of exercise on cIMT progression in patients with both type 2 diabetes and coronary artery disease (CAD). Patients with type 2 diabetes and CAD (n = 137) were randomized to exercise training or standard follow-up. The 12 month exercise program contained 150 min weekly of combined aerobic and resistance training. High-resolution ultrasonography of the distal part of the common carotid artery (CCA) was performed to measure cIMT before and after the intervention. The CCA and the carotid bulb were scanned for the presence of atherosclerotic plaques. Differences in changes between the randomized groups were calculated by one-way ANCOVA. In the total population no difference in changes of cIMT from baseline to 12 months was observed between the exercise group and controls [-0.016 mm (95 % CI -0.037 to 0.006) vs. -0.007 mm (95 % CI -0.029 to 0.015), p = 0.57]. However, there was a significant interaction between the effect of exercise training and the presence of carotid plaques (p = 0.013), and significant reduced cIMT was demonstrated in the exercise group compared with controls in patients without identified carotid plaques (n = 65) [-0.034 mm (95 % CI -0.060 to 0.008) vs. 0.013 mm (95 % CI -0.011 to 0.038), p = 0.010]. One year of exercise training in patients with type 2 diabetes and CAD did not significantly change cIMT progression. However, in patients without identified carotid plaques, beneficial effect of exercise training on cIMT progression was demonstrated.

  12. Localized measurement of optical attenuation coefficients of atherosclerotic plaque constituents by quantitative optical coherence tomography

    NARCIS (Netherlands)

    van der Meer, Freek J.; Faber, Dirk J.; Baraznji Sassoon, David M.; Aalders, Maurice C.; Pasterkamp, Gerard; van Leeuwen, Ton G.

    2005-01-01

    Optical coherence tomography (OCT) is a novel, high-resolution diagnostic tool that is capable of imaging the arterial wall and plaques. The differentiation between different types of atherosclerotic plaque is based on qualitative differences in gray levels and structural appearance. We hypothesize

  13. Phase-based vascular input function: Improved quantitative DCE-MRI of atherosclerotic plaques

    NARCIS (Netherlands)

    van Hoof, R. H. M.; Hermeling, E.; Truijman, M. T. B.; van Oostenbrugge, R. J.; Daemen, J. W. H.; van der Geest, R. J.; van Orshoven, N. P.; Schreuder, A. H.; Backes, W. H.; Daemen, M. J. A. P.; Wildberger, J. E.; Kooi, M. E.

    2015-01-01

    Purpose: Quantitative pharmacokinetic modeling of dynamic contrast-enhanced (DCE)-MRI can be used to assess atherosclerotic plaque microvasculature, which is an important marker of plaque vulnerability. Purpose of the present study was (1) to compare magnitude-versus phase-based vascular input

  14. Carotid plaque signal differences among four kinds of T1-weighted magnetic resonance imaging techniques: A histopathological correlation study

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Ayumi; Narumi, Shinsuke; Ohba, Hideki; Yamaguchi, Mao; Terayama, Yasuo [Iwate Medical University, Department of Neurology and Gerontology, Morioka (Japan); Sasaki, Makoto; Kudo, Kohsuke [Iwate Medical University, Institute for Biomedical Sciences, Morioka (Japan); Ogasawara, Kuniaki; Kobayashi, Masakazu [Iwate Medical University, Department of Neurosurgery, Morioka (Japan); Hitomi, Jiro [Iwate Medical University, Department of Anatomy, Morioka (Japan)

    2012-11-15

    Several magnetic resonance (MR) imaging techniques are used to examine atherosclerotic plaque of carotid arteries; however, the best technique for visualizing intraplaque characteristics has yet to be determined. Here, we directly compared four kinds of T1-weighted (T1W) imaging techniques with pathological findings in patients with carotid stenosis. A total of 31 patients who were candidates for carotid endarterectomy were prospectively examined using a 1.5-T MRI scanner, which produced four kinds of T1W images, including non-gated spin echo (SE), cardiac-gated black-blood (BB) fast-SE (FSE), magnetization-prepared rapid acquisition with gradient echo (MPRAGE), and source image of three-dimensional time-of-flight MR angiography (SI-MRA). The signal intensity of the carotid plaque was manually measured, and the contrast ratio (CR) against the adjacent muscle was calculated. CRs from the four imaging techniques were compared to each other and correlated with histopathological specimens. CRs of the carotid plaques mainly containing fibrous tissue, lipid/necrosis, and hemorrhage were significantly different with little overlaps (range: 0.92-1.15, 1.22-1.52, and 1.55-2.30, respectively) on non-gated SE. However, BB-FSE showed remarkable overlaps among the three groups (0.89-1.10, 1.07-1.23, and 1.01-1.42, respectively). MPRAGE could discriminate fibrous plaques from hemorrhagic plaques but not from lipid/necrosis-rich plaques: (0.77-1.07, 1.45-2.43, and 0.85-1.42, respectively). SI-MRA showed the same tendencies (1.01-1.39, 1.45-2.57, and 1.12-1.39, respectively). Among T1W MR imaging techniques, non-gated SE images can more accurately characterize intraplaque components in patients who underwent CEA when compared with cardiac-gated BB-FSE, MPRAGE, and SI-MRA images. (orig.)

  15. The role of contrast-enhanced ultrasound in risk assessment of carotid atheroma

    OpenAIRE

    Silviu Stanciu; Cristina Enciu; Ioana Răduţă; Dan Stoicescu; Adrian Anghel; Daniela Anghel; B. Olan; Lucian Ciobîcă

    2016-01-01

    Background and objective: Contrast-enhanced ultrasound, used to assess atherosclerotic carotid plaques, improves visualization of vessel wall irregularities and depicts intraplaque neovascularization. This article illustrates the use of contrast-enhanced ultrasound in the risk assessment of carotid atherosclerotic lesions, especially in challenging plaques evaluation. Materials and methods: For 23 patients with difficult duplex ultrasound examination due to carotid tortuosity o...

  16. 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.

  17. Characterization of human carotid atherosclerotic tissues imaged by combining multiple multiphoton microscopy techniques

    Science.gov (United States)

    Baria, E.; Cicchi, R.; Nesi, G.; Massi, D.; Pavone, F. S.

    2017-07-01

    We combined Second Harmonic Generation, Two-Photon Fluorescence and Fluorescence Lifetime Imaging Microscopy for studying human carotid ex vivo tissue sections affected by atherosclerosis, resulting in the discrimination of different arterial regions within the plaques.

  18. Association between pulse pressure, carotid intima-media thickness and carotid and/or iliofemoral plaque in hypertensive patients

    NARCIS (Netherlands)

    Tartiere, JM; Kesri, L; Safar, H; Girerd, [No Value; Bots, M; Safar, ME; Blacher, J

    Increased common carotid artery intima - media thickness (CCA-IMT) and carotid and/or iliofemoral (C/IF) plaque are frequent in subjects treated for hypertension, but their association with pulse pressure ( PP) has rarely been studied. Using ultrasound techniques, CCA-IMT and C/IF plaques were

  19. Serum Osteoprotegerin Is Associated With Calcified Carotid Plaque

    Science.gov (United States)

    Kwon, Ami; Choi, Yun-Seok; Choi, Yong-Won; Chung, Woo-Baek; Park, Chul-Soo; Chung, Wook-Sung; Lee, Man-Young; Youn, Ho-Joong

    2016-01-01

    Abstract Osteoprotegerin (OPG) is a kind of tumor necrosis factor, which is related to bone metabolism and vascular calcification. The increase of Osteoprotegerin concentration in serum is related to cardiovascular diseases in humans. The purpose of this study was to figure out the relevance between osteoprotegerin in serum and carotid calcification. Serum OPG concentrations were compared in 145 patients who underwent carotid sonography (average age: 68 ± 9 years old, male: female = 81:64). A calcified plaque (CP) (37 people [27%]), a noncalcified plaque (NCP) (54 people [37%]), and a nonplaque (NP) (54 people [37%]) were classified for this study. No significant differences among 3 groups were demonstrated in the distribution of age, diabetes, high blood pressure, and hyperlipidemia. Serum osteoprotegerin concentrations were significantly increased in CP group rather than NCP group or NP group; (median [interquartile range], 4016 [1410] vs 3210 [1802] pg/mL, P osteoprotegerin concentrations did not indicate a significant difference between NCP Group or NP Group. This study had proved that patient group accompanied with carotid calcification in carotid artery disease had an increased serum OPG concentration, so it could consider that OPG plays an important function on calcification related to arteriosclerosis. PMID:27082605

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-15

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

  1. Electrical impedance of layered atherosclerotic plaques on human aortas

    NARCIS (Netherlands)

    C.J. Slager (Cornelis); A.C. Phaff; C.E. Essed; N. Bom (Klaas); J.C.H. Schuurbiers (Johan); P.W.J.C. Serruys (Patrick)

    1992-01-01

    textabstractElectrical impedance measurements were performed on 13 atherosclerotic human aortic segments at 67 measuring spots in order to determine whether or not on the basis of these data a distinction can be made between atherosclerotic lesions and normal tissue. Stenosis localization and

  2. Computed tomography scan based prediction of the vulnerable carotid plaque

    DEFF Research Database (Denmark)

    Diab, Hadi Mahmoud Haider; Rasmussen, Lars Melholt; Duvnjak, Stevo

    2017-01-01

    BACKGROUND: Primary to validate a commercial semi-automated computed tomography angiography (CTA) -software for vulnerable plaque detection compared to histology of carotid endarterectomy (CEA) specimens and secondary validating calcifications scores by in vivo CTA with ex vivo non-contrast enhan......BACKGROUND: Primary to validate a commercial semi-automated computed tomography angiography (CTA) -software for vulnerable plaque detection compared to histology of carotid endarterectomy (CEA) specimens and secondary validating calcifications scores by in vivo CTA with ex vivo non...... using different HU values defining plaque components. The predictive values of CTA based detection of vulnerable plaques were calculated. Quantification of calcifications on CTA using region of interest (ROI)-function and mathematical equations was done manually, and validated by NCCT of the CEA...... in vivo CTA and ex vivo NCCT in quantification of calcification was observed, but CTA systematically underestimated calcificationsscore (CALS) with increasing calcification. CONCLUSION: The CTA-software cannot be used in risk assessment of patients, due to poor specificity and NPV. The correlation between...

  3. Tissue Doppler imaging of carotid plaque wall motion: a pilot study

    Directory of Open Access Journals (Sweden)

    Naylor A Ross

    2003-12-01

    Full Text Available Abstract Background Studies suggest the physical and mechanical properties of vessel walls and plaque may be of clinical value in the diagnosis and treatment of cardiovascular atherosclerotic disease. The purpose of this pilot study was to investigate the potential clinical application of ultrasound Tissue Doppler Imaging (TDI of Arterial Wall Motion (AWM and to quantify simple wall motion indices in normal and diseased carotid arteries. Methods 224 normal and diseased carotid arteries (0–100% stenoses were imaged in 126 patients (age 25–88 years, mean 68 ± 11. Longitudinal sections of the carotid bifurcation were imaged using a Philips HDI5000 scanner and L12-5 probe under optimized TDI settings. Temporal and spatial AWMs were analyzed to evaluate the vessel wall displacements and spatial gradients at peak systole averaged over 5 cardiac cycles. Results AWM data were successfully extracted in 91% of cases. Within the carotid bifurcation/plaque region, the maximum wall dilation at peak systole ranged from -100 to 750 microns, mean 335 ± 138 microns. Maximum wall dilation spatial gradients ranged 0–0.49, mean 0.14 ± 0.08. The AWM parameters showed a wide variation and had poor correlation with stenoses severity. Case studies illustrated a variety of pertinent qualitative and quantitative wall motion features related to the biophysics of arterial disease. Conclusion Our clinical experience, using a challenging but realistic imaging protocol, suggests the use of simple quantitative AWM measures may have limitations due to high variability. Despite this, pertinent features of AWM in normal and diseased arteries demonstrate the potential clinical benefit of the biomechanical information provided by TDI.

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

    Directory of Open Access Journals (Sweden)

    I. P. Dudanov

    2017-01-01

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

  5. Nonlinear dynamics of early atherosclerotic plaque formation may determine the efficacy of high density lipoproteins (HDL in plaque regression.

    Directory of Open Access Journals (Sweden)

    Alexander D Chalmers

    Full Text Available We use a computational model to explore the effect of foam cell accumulation on plaque regression following an increase in high density lipoprotein (HDL influx into the plaque. Atherosclerotic plaque formation is the outcome of cellular and cytokine responses to low density lipoproteins (LDL that penetrate the artery wall following an injury to the endothelium and become modified. We modelled the cells and cytokines that are most important in plaque formation using partial differential equations. The model includes monocytes and macrophages, foam cells, macrophage chemoattractants, endothelium-stimulating cytokines, modified low density lipoproteins (mod LDL and HDL. We included interactions both at the endothelium surface and inside the artery wall. The model predicts that when HDL influx into a well-established plaque with large numbers of foam cells is increased, the plaque may not regress but may continue to grow at a slower rate. If HDL influx is increased when a model plaque is recently established and has fewer foam cells, then the plaque does regress. If modLDL influx into the plaque is lowered at the same time that HDL influx increased or the capacity of the HDL to remove cholesterol from foam cells is increased, then the plaque is more likely to regress. The predictions of the model are in qualitative agreement with experimental studies in mice and rabbits. The results suggest that the intrinsic dynamics of reverse cholesterol transport by HDL are important in determining the success of HDL raising in promoting plaque regression.

  6. 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.

  7. 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

    spectrometry (MS). Among the identified proteins, two isoforms of heat shock protein 27 (HSP27), a protein recently described as a potential biomarker of atherosclerosis, were detected. However, the putative mechanisms in which HSP27 isoforms could be involved in the atherosclerotic process are unknown. Thus......, the role that phosphorylated HSP27 could play in the atherosclerotic process is actually under study. The present work shows the strategies employed to characterize the phosphorylation in the HSP27 secreted by atheroma plaque samples. The application of liquid chromatography tandem mass spectrometry (MS......-lymphocytes). These interactions can be mediated by proteins secreted from these cells, which therefore exert an important role in the atherosclerotic process. We recently described a novel strategy for the characterization of the human atherosclerotic plaque secretome, combining two-dimensional gel electrophoresis and mass...

  8. Functionalization of gadolinium metallofullerenes for detecting atherosclerotic plaque lesions by cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Dellinger Anthony

    2013-01-01

    Full Text Available Abstract Background The hallmark of atherosclerosis is the accumulation of plaque in vessel walls. This process is initiated when monocytic cells differentiate into macrophage foam cells under conditions with high levels of atherogenic lipoproteins. Vulnerable plaque can dislodge, enter the blood stream, and result in acute myocardial infarction and stroke. Imaging techniques such as cardiovascular magnetic resonance (CMR provides one strategy to identify patients with plaque accumulation. Methods We synthesized an atherosclerotic-targeting contrast agent (ATCA in which gadolinium (Gd-containing endohedrals were functionalized and formulated into liposomes with CD36 ligands intercalated into the lipid bilayer. In vitro assays were used to assess the specificity of the ATCA for foam cells. The ability of ATCA to detect atherosclerotic plaque lesions in vivo was assessed using CMR. Results The ATCA was able to detect scavenger receptor (CD36-expressing foam cells in vitro and were specifically internalized via the CD36 receptor as determined by focused ion beam/scanning electron microscopy (FIB-SEM and Western blotting analysis of CD36 receptor-specific signaling pathways. The ATCA exhibited time-dependent accumulation in atherosclerotic plaque lesions of ApoE −/− mice as determined using CMR. No ATCA accumulation was observed in vessels of wild type (C57/b6 controls. Non-targeted control compounds, without the plaque-targeting moieties, were not taken up by foam cells in vitro and did not bind plaque in vivo. Importantly, the ATCA injection was well tolerated, did not demonstrate toxicity in vitro or in vivo, and no accumulation was observed in the major organs. Conclusions The ATCA is specifically internalized by CD36 receptors on atherosclerotic plaque providing enhanced visualization of lesions under physiological conditions. These ATCA may provide new tools for physicians to non-invasively detect atherosclerotic disease.

  9. Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability

    DEFF Research Database (Denmark)

    Olson, Fredrik J; Thurison, Tine; Ryndel, Mikael

    2009-01-01

    OBJECTIVES:: To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability. DESIGN AND METHODS:: Plasma concentrations of suPAR(I-III), suPAR(II-III) and uPAR(I) were measured by time-resolved fluorescence...... immunoassays in Caucasian patients operated for symptomatic carotid atherosclerosis (n=255). Local suPAR release from plaques into the circulation was assessed in plasma passing retrogradely over the plaque in the carotid artery, collected during surgery (n=7). RESULTS:: The suPAR(I-III) (P=0.03) and su......PAR(II-III) (P=0.006) concentrations were higher after ischemic strokes and transient ischemic attacks, i.e., clinical subgroups associated with poorer prognosis and a less stable plaque phenotype, than after amaurosis fugax. Slightly elevated suPAR(I-III) levels were found in plasma from the carotid lesion...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    Fibrous cap smooth muscle cells (SMCs) protect atherosclerotic lesions from rupturing and causing thrombosis, while other plaque SMCs may have detrimental roles in plaque development. To gain insight into recruitment of different plaque SMCs, we mapped their clonal architecture in aggregation...... in the cap and heterogeneous ACTA2– SMCs in the plaque interior, including chondrocyte-like cells and cells with intracellular lipid and crystalline material. Fibrous cap SMCs were invariably arranged in endothelium-aligned clonal sheets, confirming results in the aggregation chimeras. Analysis of the clonal...

  11. Athero Express : ATHERO-sclerotic plaque EXPRESSion in relation to vascular events and patient characteristics

    NARCIS (Netherlands)

    Verhoeven, B.A.N.

    2006-01-01

    Athero-Express is a tissue bank study, designed to investigate the expression of atherosclerotic derived biological variables in relation to the long-term outcome of patients undergoing carotid endarterectomy. Its design includes both cross-sectional and follow-up studies, the results from which

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

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

    2013-01-01

    Objectives: Blood pool FDG activity can cloud the atherosclerotic plaque FDG signal. Over time, blood pool FDG activity declines. Therefore, delayed time point FDG PET CT imaging can potentially enhance the assessment of atherosclerotic plaque inflammation. Methods: Twelve healthy volunteers...... without traditional cardiovascular risk factors and three subjects with angina pectoris were prospectively assessed by dual time point 18-FDG PET CT imaging at 90 and 180 minutes after tracer injection. The ratio between aortic SUVmax and the blood pool SUVmean (TBR) was calculated to show the change...

  13. In vivo transfer of lipoprotein(a) into human atherosclerotic carotid arterial intima

    DEFF Research Database (Denmark)

    Nielsen, Lars Bo; Grønholdt, Marie-Louise; Schroeder, T V

    1997-01-01

    The aim of this study was to compare the atherogenic potential of lipoprotein(a) [Lp(a)] and LDL by measuring the intimal clearance of these two plasma lipoproteins in the atherosclerotic intima of the human carotid artery in vivo. Autologous 131I-Lp(a) and 125I-LDL were mixed and reinjected intr...

  14. [Carotid artery plaque in patients with disorders of glucose regulation].

    Science.gov (United States)

    Savić, Z N; Djordjević, P B; Ilić, M M; Popović, S S; Dimitrijević-Srećković, V; Canović, F M; Brajović, M D

    2008-01-01

    The aim of this study was measurement of artery intima media thickness (IMT) and plaques as an early indicator of atherosclerosis in diabetics comparing with other risk factors of carotid artery. 110 pts: 50 with Diabetes Mellitus, type 1 (25) and type 2 (25), 20 pts with glucose intolerance, 20 pts with type 2 de novo and 20 pts obese without diabetes. Ultrasound examination (using 7.5 MHz sound on Toshiba SSA-270A) end measurement of intima-media ticknes (IMT) were performed on Carotis communis (CCA), bifurcation and distal from bifurcation to a.carotis intern (ACI), expressed in mm. Plaques were correlated with other common factors age, BP, lipid parameters (Chol, HDL, LDL, Triglycerides), smoks, alcoholism and obese (BMI). The authors used 2 test and Spearman's correlation. The lowest percent of plaques was found in group with type DM 1. The highest percent of plaques was found in type DM 2. Statistically there is highly significant difference between plaques founded on type 2 DM and types 2 DM de novo and on other types. DM is not an independent risk factor for developing of macroangiopathic changes an arterial walls, but their appirience are more presenting in diabetic patients. The highest number of plaques are presenting DM type 2 (29.6%), and after type 2 de novo (26.8%), the next highest position of plaques were in patients with obese but without DM and intolerantio glucosae (IFG+IGT) (17.1%) and type 1 DM (9.8%). Risk factors were presented in following percentage: Obese 80.5% pts; hyperlipidema 53.7% pts; HTA 51.3%; smoking 51.2% pts and alchocholism 2.4% pts. According to these results, all risk factors were included in patophysiology of plack forming except alcoholism. Influences of these risk faktors are very importance and their synergic action lids to their rapid appirience and clinical manifestations. DM has specific position in patophisiology of atherosclerosis.

  15. Akt2/LDLr double knockout mice display impaired glucose tolerance and develop more complex atherosclerotic plaques than LDLr knockout mice

    NARCIS (Netherlands)

    Rensing, Katrijn L.; de Jager, Saskia C. A.; Stroes, Erik S.; Vos, Mariska; Twickler, Marcel Th B.; Dallinga-Thie, Geesje M.; de Vries, Carlie J. M.; Kuiper, Johan; Bot, Ilze; von der Thüsen, Jan H.

    2014-01-01

    To characterize the phenotype of Akt2/low-density-lipoprotein receptor double knockout (dKO) (Akt2/LDLr dKO) mice with respect to insulin resistance and features of atherosclerotic plaque progression. Metabolic profile and atherosclerotic plaque progression were compared between LDLr KO mice and

  16. Hybrid technologies in surgical treatment of patients with concomitant atherosclerotic lesions of carotid and coronary arteries

    Directory of Open Access Journals (Sweden)

    А. М. Чернявский

    2015-10-01

    Full Text Available Cardiovascular diseases, which have their origins in atherosclerosis, are the "leaders" in morbidity and mortality among the population in many countries. Given the increase of elderly people in the population, it is important to choose the best strategy for surgical treatment of patients with combined atherosclerotic lesions of several arteries (coronary arteries, carotid arteries, peripheral arteries of the lower extremities, atherosclerosis visceral branches of the abdominal aorta. Currently, there is yet no common approach to the timing and sequence of revascularization surgery in this group of patients. The rapid development of endovascular techniques enables us to carry out the so-called hybrid procedures in patients with atherosclerotic lesions of several arteries. In this article we analyze different strategies that are used to manage patients with both coronary and carotid arteries atherosclerotic lesions.

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

    DEFF Research Database (Denmark)

    Barascuk, Natasha; Skjøt-Arkil, Helene; Register, Thomas C

    2010-01-01

    BACKGROUND: Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular...... 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......-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women...

  18. ADAM-10 could mediate cleavage of N-cadherin promoting apoptosis in human atherosclerotic lesions leading to vulnerable plaque: a morphological and immunohistochemical study.

    Science.gov (United States)

    Musumeci, Giuseppe; Coleman, Raymond; Imbesi, Rosa; Magro, Gaetano; Parenti, Rosalba; Szychlinska, Marta Anna; Scuderi, Rosario; Cinà, Claudio Salvatore; Castorina, Sergio; Castrogiovanni, Paola

    2014-09-01

    Atherosclerosis remains a major cause of mortality. Whereas the histopathological progression of atherosclerotic lesions is well documented, much less is known about the development of unstable or vulnerable plaque, which can rupture leading to thrombus, luminal occlusion and infarct. Apoptosis in the fibrous cap, which is rich in vascular smooth muscle cells (VSMCs) and macrophages, and its subsequent weakening or erosion seems to be an important regulator of plaque stability. The aim of our study was to improve our knowledge on the biological mechanisms that cause plaque instability in order to develop new therapies to maintain atherosclerotic plaque stability and avoid its rupture. In our study, we collected surgical specimens from atherosclerotic plaques in the right or left internal carotid artery of 62 patients with evident clinical symptoms. Histopathology and histochemistry were performed on wax-embedded sections. Immunohistochemical localization of caspase-3, N-cadherin and ADAM-10 was undertaken in order to highlight links between apoptosis, as expressed by caspase-3 immunostaining, and possible roles of N-cadherin, a cell-cell junction protein in VSMCs and macrophages that provides a pro-survival signal reducing apoptosis, and ADAM-10, a "disintegrin and metalloproteases" that is able to cleave N-cadherin in glioblastomas. Our results showed that when apoptosis, expressed by caspase-3 immunostaining, increased in the fibrous cap, rich in VSMCs and macrophages, the expression of N-cadherin decreased. The decreased N-cadherin expression, in turn, was linked to increased ADAM-10 expression. This study shows that apoptotic events are probably involved in the vulnerability of atherosclerotic plaque. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men.

    Science.gov (United States)

    Zanni, Markella V; Abbara, Suhny; Lo, Janet; Wai, Bryan; Hark, David; Marmarelis, Eleni; Grinspoon, Steven K

    2013-05-15

    Among HIV-infected patients, high rates of myocardial infarction (MI) and sudden cardiac death have been observed. Exploring potential underlying mechanisms, we used multidetector spiral coronary computed tomography angiography (coronary CTA) to compare atherosclerotic plaque morphology in HIV-infected patients and non-HIV-infected controls. Coronary atherosclerotic plaques visualized by CTA in HIV-infected (101) and non-HIV-infected (41) men without clinically apparent heart disease matched on cardiovascular risk factors were analyzed for three vulnerability features: low attenuation, positive remodeling, and spotty calcification. Ninety-five percent of HIV-infected patients were receiving ART (median duration 7.9 years) and had well controlled disease (median CD4 cell count, 473 cells/μl; median HIV RNA <50 copies/ml). Age and traditional cardiovascular risk factors were similar in HIV-infected patients and controls. Among the HIV-infected (versus control) group, there was a higher prevalence of patients with at least one: low attenuation plaque (22.8 versus 7.3%, P = 0.02), positively remodeled plaque (49.5 versus 31.7%, P = 0.05) and high-risk 3-feature plaque (7.9 versus 0%, P = 0.02). Moreover, patients in the HIV-infected (versus control) group demonstrated a higher number of low attenuation plaques (P = 0.01) and positively remodeled plaques (P = 0.03) per patient. Our data demonstrate an increased prevalence of vulnerable plaque features among relatively young HIV-infected patients. Differences in coronary atherosclerotic plaque morphology - namely, increased vulnerable plaque among HIV-infected patients - are here for the first time reported and may contribute to increased rates of MI and sudden cardiac death in this population.

  20. Platelet activation, function, and reactivity in atherosclerotic carotid artery stenosis: a systematic review of the literature.

    LENUS (Irish Health Repository)

    Kinsella, J A

    2012-09-27

    An important proportion of transient ischemic attack or ischemic stroke is attributable to moderate or severe (50-99%) atherosclerotic carotid stenosis or occlusion. Platelet biomarkers have the potential to improve our understanding of the pathogenesis of vascular events in this patient population. A detailed systematic review was performed to collate all available data on ex vivo platelet activation and platelet function\\/reactivity in patients with carotid stenosis. Two hundred thirteen potentially relevant articles were initially identified; 26 manuscripts met criteria for inclusion in this systematic review. There was no consistent evidence of clinically informative data from urinary or soluble blood markers of platelet activation in patients with symptomatic moderate or severe carotid stenosis who might be considered suitable for carotid intervention. Data from flow cytometry studies revealed evidence of excessive platelet activation in patients in the early, sub-acute, or late phases after transient ischemic attack or stroke in association with moderate or severe carotid stenosis and in asymptomatic moderate or severe carotid stenosis compared with controls. Furthermore, pilot data suggest that platelet activation may be increased in recently symptomatic than in asymptomatic severe carotid stenosis. Excessive platelet activation and platelet hyperreactivity may play a role in the pathogenesis of first or subsequent transient ischemic attack or stroke in patients with moderate or severe carotid stenosis. Larger longitudinal studies assessing platelet activation status with flow cytometry and platelet function\\/reactivity in symptomatic vs. asymptomatic carotid stenosis are warranted to improve our understanding of the mechanisms responsible for transient ischemic attack or stroke.

  1. Ultrasound analysis of gray-scale median value of carotid plaques is a useful reference index for cerebro-cardiovascular events in patients with type 2 diabetes.

    Science.gov (United States)

    Ariyoshi, Kyoko; Okuya, Shigeru; Kunitsugu, Ichiro; Matsunaga, Kimie; Nagao, Yuko; Nomiyama, Ryuta; Takeda, Komei; Tanizawa, Yukio

    2015-01-01

    Measurements of plaque echogenicity, the gray-scale median (GSM), were shown to correlate inversely with risk factors for cerebro-cardiovascular disease (CVD). The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is a potential predictor of CVD risk. In the present study, we assessed the usefulness of carotid plaque GSM values and EPA/AA ratios in atherosclerotic diabetics. A total of 84 type 2 diabetics with carotid artery plaques were enrolled. On admission, platelet aggregation and lipid profiles, including EPA and AA, were examined. Using ultrasound, mean intima media thickness and plaque score were measured in carotid arteries. Plaque echogenicity was evaluated using computer-assisted quantification of GSM. The patients were then further observed for approximately 3 years. Gray-scale median was found to be a good marker of CVD events. On multivariate logistic regression analysis, GSM values, an association of EPA/AA with CVD events could not be statistically confirmed. The present results suggest the GSM value to be useful as a reference index for CVD events in high-risk atherosclerotic diabetics. Associations of the EPA/AA ratio with known CVD risk factors warrant a larger and more extensive study to show the usefulness of this parameter.

  2. Soluble urokinase plasminogen activator receptor: a risk factor for carotid plaque, stroke, and coronary artery disease.

    Science.gov (United States)

    Persson, Margaretha; Östling, Gerd; Smith, Gustav; Hamrefors, Viktor; Melander, Olle; Hedblad, Bo; Engström, Gunnar

    2014-01-01

    Recent studies indicate that the urokinase system could have an important role in atherogenesis and plaque rupture. The relationships among the soluble urokinase plasminogen activator receptor (suPAR), carotid plaque, and incidence of ischemic stroke and coronary artery disease (CAD) events were studied in a prospective cohort. Occurrence of carotid plaque and plasma levels of suPAR were assessed in 5166 men and women, aged 45 to 68 years, participating in the Malmö Diet and Cancer study. Incidences of ischemic stroke and CAD were monitored during a mean follow-up of 15 years. Subjects with carotid plaque had significantly higher levels of suPAR compared with those without carotid plaque. suPAR was associated with increased incidence of ischemic stroke (hazard ratio [HR] for third versus first tertile, 1.50; 95% confidence interval [CI], 1.06-2.11) and CAD (HR, 1.55; 95% CI, 1.13-2.13) after adjustment for risk factors. The risk factor-adjusted HR for ischemic stroke was 2.21 (95% CI, 1.52-3.22) in subjects with carotid plaque and high suPAR (ie, third tertile) and 1.51 (95% CI, 1.05-2.17) in subjects with carotid plaque and low suPAR compared with those without carotid plaque and low suPAR (reference). High levels of suPAR significantly increased the risk of ischemic stroke and CAD in subjects with carotid plaque. suPAR is associated with increased occurrence of carotid plaque and increased incidence of ischemic stroke and CAD. Presence of both elevated levels of suPAR and carotid plaque increases the risk of ischemic stroke in an additive way.

  3. Plaque inflammation and unstable morphology are associated with early stroke recurrence in symptomatic carotid stenosis.

    LENUS (Irish Health Repository)

    Marnane, Michael

    2014-03-01

    Although symptomatic carotid stenosis is associated with 3-fold increased risk of early stroke recurrence, the pathophysiologic mechanisms of high early stroke risk have not been established. We aimed to investigate the relationship between early stroke recurrence after initial symptoms and histological features of plaque inflammation and instability in resected carotid plaque.

  4. Cytomegalovirus localization in atherosclerotic plaques is associated with acute coronary syndromes: report of 105 patients.

    Science.gov (United States)

    Izadi, Morteza; Fazel, Mozhgan; Saadat, Seyed Hassan; Nasseri, Mohammad Hassan; Ghasemi, Mojtaba; Dabiri, Hossein; Aryan, Reza Safi; Esfahani, Ali Akbar; Ahmadi, Ali; Kazemi-Saleh, Davood; Kalantar-Motamed, Mohammad Hassan; Taheri, Saeed

    2012-01-01

    It has been shown that cytomegalovirus (CMV) is present in coronary atherosclerotic plaques, but the clinical relevance of this presence remains to be elucidated. In this study we sought to examine CMV infection in atherosclerosis patients defined by different methods and to identify the clinical significance of CMV replication in the atherosclerotic plaques. The study included 105 consecutive patients who were admitted to our department and underwent coronary artery bypass grafting (CABG) surgical interventions. Coronary atherosclerotic specimens as well as 53 specimens from the mamillary artery of these same patients were analyzed. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods were used for evaluations. The CMV PCR test result was positive for 28 (26.7%) of patients with coronary artery atherosclerosis. After adjusting for other risk factors, coronary artery disease patients with a history of acute coronary syndrome were more likely to be positive for CMV PCR test (P=0.027; odds ratio: 4.2; 95% CI: 1.18-15.0). They were also more likely to have a positive family history for cardiovascular diseases (CVD). This study confirms previous evidence about the replication of CMV virus in the atherosclerotic plaques of coronary arteries and brings clinical significance to this observation by showing a higher prevalence of acute coronary syndromes in those patients with CMV-infected plaques. Our study also suggests a familial vulnerability to CMV replication in the coronary artery walls.

  5. Proteomic analysis of differential protein expression in human atherosclerotic plaque progression

    NARCIS (Netherlands)

    Donners, Marjo M. P. C.; Verluyten, Monique J.; Bouwman, Freek G.; Mariman, Edwin C. M.; Devreese, Bart; Vanrobaeys, Frank; van Beeumen, Jozef; van den Akker, Luc H. J. M.; Daemen, Mat J. A. P.; Heeneman, Sylvia

    2005-01-01

    In this study, differential protein expression was assessed during human atherosclerotic plaque progression. A multifaceted approach was used in which differential protein expression was studied by two-dimensional (2D) gel electrophoresis and validated in individual patients using western blotting

  6. How radiation influences atherosclerotic plaque development. A biophysical approach in ApoE{sup -/-} mice

    Energy Technology Data Exchange (ETDEWEB)

    Kloosterman, Astrid; Dillen, Teun van; Dekkers, Fieke [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Safety and Security, Bilthoven (Netherlands); Bijwaard, Harmen [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Safety and Security, Bilthoven (Netherlands); Inholland University of Applied Sciences, Medical Technology Research Group, Haarlem (Netherlands); Heeneman, Sylvia [Maastricht University Medical Center, Experimental Vascular Pathology group, Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Hoving, Saske; Stewart, Fiona A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Biological Stress Response (H3), Amsterdam (Netherlands)

    2017-11-15

    Atherosclerosis is the development of lipid-laden plaques in arteries and is nowadays considered as an inflammatory disease. It has been shown that high doses of ionizing radiation, as used in radiotherapy, can increase the risk of development or progression of atherosclerosis. To elucidate the effects of radiation on atherosclerosis, we propose a mathematical model to describe radiation-promoted plaque development. This model distinguishes itself from other models by combining plaque initiation and plaque growth, and by incorporating information from biological experiments. It is based on two consecutive processes: a probabilistic dose-dependent plaque initiation process, followed by deterministic plaque growth. As a proof of principle, experimental plaque size data from carotid arteries from irradiated ApoE{sup -/-} mice was used to illustrate how this model can provide insight into the underlying biological processes. This analysis supports the promoting role for radiation in plaque initiation, but the model can easily be extended to include dose-related effects on plaque growth if available experimental data would point in that direction. Moreover, the model could assist in designing future biological experiments on this research topic. Additional biological data such as plaque size data from chronically-irradiated mice or experimental data sets with a larger variety in biological parameters can help to further unravel the influence of radiation on plaque development. To the authors' knowledge, this is the first biophysical model that combines probabilistic and mechanistic modeling which uses experimental data to investigate the influence of radiation on plaque development. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Raiyan T Zaman

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

  8. 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.

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

    Science.gov (United States)

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

    2017-02-01

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

  10. 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.

  11. Optimization of dual-wavelength intravascular photoacoustic imaging of atherosclerotic plaques using Monte Carlo optical modeling

    Science.gov (United States)

    Dana, Nicholas; Sowers, Timothy; Karpiouk, Andrei; Vanderlaan, Donald; Emelianov, Stanislav

    2017-10-01

    Coronary heart disease (the presence of coronary atherosclerotic plaques) is a significant health problem in the industrialized world. A clinical method to accurately visualize and characterize atherosclerotic plaques is needed. Intravascular photoacoustic (IVPA) imaging is being developed to fill this role, but questions remain regarding optimal imaging wavelengths. We utilized a Monte Carlo optical model to simulate IVPA excitation in coronary tissues, identifying optimal wavelengths for plaque characterization. Near-infrared wavelengths (≤1800 nm) were simulated, and single- and dual-wavelength data were analyzed for accuracy of plaque characterization. Results indicate light penetration is best in the range of 1050 to 1370 nm, where 5% residual fluence can be achieved at clinically relevant depths of ≥2 mm in arteries. Across the arterial wall, fluence may vary by over 10-fold, confounding plaque characterization. For single-wavelength results, plaque segmentation accuracy peaked at 1210 and 1720 nm, though correlation was poor (primary wavelength (≈1.0). Results suggest that, without flushing the luminal blood, a primary and secondary wavelength near 1210 and 1350 nm, respectively, may offer the best implementation of dual-wavelength IVPA imaging. These findings could guide the development of a cost-effective clinical system by highlighting optimal wavelengths and improving plaque characterization.

  12. Non-calcified coronary atherosclerotic plaque characterization by dual energy computed tomography.

    Science.gov (United States)

    Yamak, Didem; Panse, Prasad; Pavlicek, William; Boltz, Thomas; Akay, Metin

    2014-05-01

    Coronary heart disease (CHD) is the most prevalent cause of death worldwide. Atherosclerosis which is the condition of plaque buildup on the inside of the coronary artery wall is the main cause of CHD. Rupture of unstable atherosclerotic coronary plaque is known to be the cause of acute coronary syndrome. Vulnerability of atherosclerotic plaque has been related to a large lipid core covered by a fibrous cap. Non-invasive assessment of plaque characterization is necessary due to prognostic importance of early stage identification. The purpose of this study is to use the additional attenuation data provided by dual energy computed tomography (DECT) for plaque characterization. We propose to train supervised learners on pixel values recorded from DECT monochromatic X-ray and material basis pairs images, for more precise classification of fibrous and lipid plaques. The interaction of the pixel values from different image types is taken into consideration, as single pixel value might not be informative enough to separate fibrous from lipid. Organic phantom plaques scanned in a fabricated beating heart phantom were used as ground truth to train the learners. Our results show that support vector machines, artificial neural networks and random forests provide accurate results both on phantom and patient data.

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

    Science.gov (United States)

    Jacobsen, Kevin; Lund, Marie Bek; Shim, Jeong; Gunnersen, Stine; Füchtbauer, Ernst-Martin; Kjolby, Mads; Carramolino, Laura; Bentzon, Jacob Fog

    2017-10-05

    Fibrous cap smooth muscle cells (SMCs) protect atherosclerotic lesions from rupturing and causing thrombosis, while other plaque SMCs may have detrimental roles in plaque development. To gain insight into recruitment of different plaque SMCs, we mapped their clonal architecture in aggregation chimeras of eGFP+Apoe-/- and Apoe-/- mouse embryos and in mice with a mosaic expression of fluorescent proteins in medial SMCs that were rendered atherosclerotic by PCSK9-induced hypercholesterolemia. Fibrous caps in aggregation chimeras were found constructed from large, endothelial-aligned layers of either eGFP+ or nonfluorescent SMCs, indicating substantial clonal expansion of a few cells. Similarly, plaques in mice with SMC-restricted Confetti expression showed oligoclonal SMC populations with little intermixing between the progeny of different medial SMCs. Phenotypes comprised both ACTA2+ SMCs in the cap and heterogeneous ACTA2- SMCs in the plaque interior, including chondrocyte-like cells and cells with intracellular lipid and crystalline material. Fibrous cap SMCs were invariably arranged in endothelium-aligned clonal sheets, confirming results in the aggregation chimeras. Analysis of the clonal structure showed that a low number of local medial SMCs partake in atherosclerosis and that single medial SMCs can produce several different SMC phenotypes in plaque. The combined results show that few medial SMCs proliferate to form the entire phenotypically heterogeneous plaque SMC population in murine atherosclerosis.

  14. The effect of aging on atherosclerotic plaque inflammation and molecular calcification: A PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Simonsen, Jane Angel

    Aim: Aging is an important independent risk factor for the inception and maturation of atherosclerotic plaques. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and molecular calcification. Methods: Thirteen healthy volunteers without traditional......SUV) [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...... polynomial regression established that aging is a strong predictor of the degree of aortic plaque inflammation (R2 = 0.71, F statistic = 11.98, P = 0.002). A linear relationship was observed between aging and molecular calcification. Linear regression established that aging is a predictor of both the degree...

  15. Molecular imaging of atherosclerotic plaques with technetium-99m-labelled antisense oligonucleotides

    International Nuclear Information System (INIS)

    Qin Guangming; Zhang Yongxue; Cao Wei; An Rui; Gao Zairong; Xu Wendai; Zhang Kaijun; Li Guiling; Li Shuren

    2005-01-01

    The purpose of this study was to visualise experimental atherosclerotic lesions using radiolabelled antisense oligonucleotides (ASONs). Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for approximately 60 days. In vivo and ex vivo imaging was performed in atherosclerotic rabbits and normal control rabbits after i.v. injection of 92.5±18.5 MBq 99m Tc-labelled ASON or 99m Tc-labelled sense oligonucleotides. Immediately after the in vivo imaging, the animals were sacrificed and ex vivo imaging of the aortic specimens was performed. Biodistribution of radiolabelled c-mycASON was evaluated in vivo in atherosclerotic rabbits. Planar imaging revealed accumulation of 99m Tc-labelled c-mycASON in atherosclerotic lesions along the artery wall. Ex vivo imaging further demonstrated that the area of activity accumulation matched the area of atherosclerotic lesions. In contrast, no atherosclerotic lesions were found in the vessel wall and no positive imaging results were obtained in animals of the control group. This molecular imaging approach has potential for non-invasive imaging of atherosclerotic plaques at an early stage. (orig.)

  16. Red Blood Cell Eicosapentaenoic Acid Inversely Relates to MRI-Assessed Carotid Plaque Lipid Core Burden in Elders at High Cardiovascular Risk

    Directory of Open Access Journals (Sweden)

    Núria Bargalló

    2017-09-01

    Full Text Available Supplemental marine omega-3 eicosapentaenoic acid (EPA has an anti-atherosclerotic effect. Clinical research on EPA supplied by the regular diet and atherosclerosis is scarce. In the framework of the PREvención con DIeta MEDiterránea (PREDIMED trial, we conducted a cross-sectional study in 161 older individuals at high vascular risk grouped into different stages of carotid atherosclerosis severity, including those without ultrasound-detected atheroma plaque (n = 38, with plaques <2.0 mm thick (n = 65, and with plaques ≥2.0 mm (n = 79. The latter were asked to undergo contrast-enhanced 3T magnetic resonance imaging (MRI and were subsequently grouped into absence (n = 31 or presence (n = 27 of MRI-detectable plaque lipid, a main feature of unstable atheroma plaques. We determined the red blood cell (RBC proportion of EPA (a valid marker of long-term EPA intake at enrolment by gas chromatography. In multivariate models, EPA related inversely to MRI-assessed plaque lipid volume, but not to maximum intima-media thickness of internal carotid artery, plaque burden, or MRI-assessed normalized wall index. The inverse association between EPA and plaque lipid content in patients with advanced atherosclerosis supports the notion that this fatty acid might improve cardiovascular health through stabilization of advanced atheroma plaques.

  17. Red Blood Cell Eicosapentaenoic Acid Inversely Relates to MRI-Assessed Carotid Plaque Lipid Core Burden in Elders at High Cardiovascular Risk

    Science.gov (United States)

    Bargalló, Núria; Gilabert, Rosa; Romero-Mamani, Edwin-Saúl; Calder, Philip C.; Fitó, Montserrat; Estruch, Ramon; Ros, Emilio; Sala-Vila, Aleix

    2017-01-01

    Supplemental marine omega-3 eicosapentaenoic acid (EPA) has an anti-atherosclerotic effect. Clinical research on EPA supplied by the regular diet and atherosclerosis is scarce. In the framework of the PREvención con DIeta MEDiterránea (PREDIMED) trial, we conducted a cross-sectional study in 161 older individuals at high vascular risk grouped into different stages of carotid atherosclerosis severity, including those without ultrasound-detected atheroma plaque (n = 38), with plaques <2.0 mm thick (n = 65), and with plaques ≥2.0 mm (n = 79). The latter were asked to undergo contrast-enhanced 3T magnetic resonance imaging (MRI) and were subsequently grouped into absence (n = 31) or presence (n = 27) of MRI-detectable plaque lipid, a main feature of unstable atheroma plaques. We determined the red blood cell (RBC) proportion of EPA (a valid marker of long-term EPA intake) at enrolment by gas chromatography. In multivariate models, EPA related inversely to MRI-assessed plaque lipid volume, but not to maximum intima-media thickness of internal carotid artery, plaque burden, or MRI-assessed normalized wall index. The inverse association between EPA and plaque lipid content in patients with advanced atherosclerosis supports the notion that this fatty acid might improve cardiovascular health through stabilization of advanced atheroma plaques. PMID:28930197

  18. Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET)

    DEFF Research Database (Denmark)

    Graebe, M; Pedersen, Sune Folke; Borgwardt, L

    2008-01-01

    OBJECTIVES: Atherosclerosis is recognised as an inflammatory disease, and new diagnostic tools are warranted to evaluate plaque inflammatory activity and risk of cardiovascular events. We investigated [18]-fluorodeoxyglucose (FDG) uptake in vulnerable carotid plaques visualised by positron emission...... tomography (PET). Uptake was correlated to quantitative gene expression of known markers of inflammation and plaque vulnerability. METHODS: Ten patients with recent transient ischaemic attack and carotid artery stenosis (>50%) underwent combined FDG-PET and computed tomography angiography (CTA) the day...

  19. Circulating immunoglobulins are not associated with intraplaque mast cell number and other vulnerable plaque characteristics in patients with carotid artery stenosis.

    Directory of Open Access Journals (Sweden)

    Sanne Willems

    Full Text Available BACKGROUND: Recently, we have shown that intraplaque mast cell numbers are associated with atherosclerotic plaque vulnerability and with future cardiovascular events, which renders inhibition of mast cell activation of interest for future therapeutic interventions. However, the endogenous triggers that activate mast cells during the progression and destabilization of atherosclerotic lesions remain unidentified. Mast cells can be activated by immunoglobulins and in the present study, we aimed to establish whether specific immunoglobulins in plasma of patients scheduled for carotid endarterectomy were related to (activated intraplaque mast cell numbers and plasma tryptase levels. In addition, the levels were related to other vulnerable plaque characteristics and baseline clinical data. METHODS AND RESULTS: OxLDL-IgG, total IgG and total IgE levels were measured in 135 patients who underwent carotid endarterectomy. No associations were observed between the tested plasma immunoglobulin levels and total mast cell numbers in atherosclerotic plaques. Furthermore, no associations were found between IgG levels and the following plaque characteristics: lipid core size, degree of calcification, number of macrophages or smooth muscle cells, amount of collagen and number of microvessels. Interestingly, statin use was negatively associated with plasma IgE and oxLDL-IgG levels. CONCLUSIONS: In patients suffering from carotid artery disease, total IgE, total IgG and oxLDL-IgG levels do not associate with plaque mast cell numbers or other vulnerable plaque histopathological characteristics. This study thus does not provide evidence that the immunoglobulins tested in our cohort play a role in intraplaque mast cell activation or grade of atherosclerosis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

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

    Science.gov (United States)

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

    2013-02-27

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

  2. Inraoperative and Histological Visualization of Disrupted Vulnerable Plaques following Diagnostic Angiography of Moderate Carotid Stenosis

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    Tatsushi Mutoh

    2010-01-01

    Full Text Available Background. Digital subtraction angiography (DSA remains an important tool for diagnosis of carotid stenosis but is associated with risk for periprocedural complications. This is the first report of direct intraoperative and histolopathologic visualization of DSA-related carotid plaque disruption. Case. A 64-year-old man diagnosed to have a 60% right carotid stenosis received diagnostic DSA for therapeutic decision-making. He developed transient left hand numbness and weakness immediately after the procedure. Intraoperative imaging during carotid endarterectomy revealed a fragile plaque with sharp surface laceration and intraplaque hemorrhage at the bifurcation. Microscopy of the specimen demonstrated a large atheromatous plaque with fibrous hypertrophy and intraplaque hemorrhage filled with recent hemorrhagic debris. Conclusion. The visualized carotid lesion was more serious than expected, warning the danger of embolization or occlusion associated with the catheter maneuvers. Thus the highest level of practitioner training and technical expertise that ensures precise assessment of plaque characteristics should be encouraged.

  3. Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques

    Energy Technology Data Exchange (ETDEWEB)

    Tang, T.Y.; Sadat, U. [Cambridge University Hospitals NHS Foundation Trust, University Department of Radiology, Cambridge (United Kingdom); Cambridge University Hospitals NHS Foundation Trust, Cambridge Vascular Unit, Cambridge (United Kingdom); Patterson, A.J.; Graves, M.J.; Howarth, S.P.S.; U-King-Im, J.M.; Li, Z.Y.; Young, V.E.; Gillard, J.H. [Cambridge University Hospitals NHS Foundation Trust, University Department of Radiology, Cambridge (United Kingdom); Miller, S.R. [GlaxoSmithKline, Biostatistics and Data Sciences, Harlow (United Kingdom); Walsh, S.R.; Boyle, J.R.; Gaunt, M.E. [Cambridge University Hospitals NHS Foundation Trust, Cambridge Vascular Unit, Cambridge (United Kingdom)

    2009-07-15

    Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI has been shown to be a useful modality to image activated macrophages in vivo, which are principally responsible for plaque inflammation. This study determined the optimum imaging time-window to detect maximal signal change post-USPIO infusion using T{sub 1}-weighted (T{sub 1}w), T{sub 2}*-weighted (T{sub 2}*w) and quantitative T{sub 2}* (qT{sub 2}*) imaging. Six patients with an asymptomatic carotid stenosis underwent high resolution T{sub 1}w, T{sub 2}*w and qT{sub 2}* MR imaging of their carotid arteries at 1.5 T. Imaging was performed before and at 24, 36, 48, 72 and 96 h after USPIO (Sinerem trademark, Guerbet, France) infusion. Each slice showing atherosclerotic plaque was manually segmented into quadrants and signal changes in each quadrant were fitted to an exponential power function to model the optimum time for post-infusion imaging. The power function determining the mean time to convergence for all patients was 46, 41 and 39 h for the T{sub 1}w, T{sub 2}*w and qT{sub 2}* sequences, respectively. When modelling each patient individually, 90% of the maximum signal intensity change was observed at 36 h for three, four and six patients on T{sub 1}w, T{sub 2}*w and qT{sub 2}*, respectively. The rates of signal change decrease after this period but signal change was still evident up to 96 h. This study showed that a suitable imaging window for T{sub 1}w, T{sub 2}*w and qT{sub 2}* signal changes post-USPIO infusion was between 36 and 48 h. Logistically, this would be convenient in bringing patients back for one post-contrast MRI, but validation is required in a larger cohort of patients. (orig.)

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

    International Nuclear Information System (INIS)

    Broisat, A.

    2005-04-01

    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, 201 Tl presents some drawbacks. 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 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, 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)

  5. Biomarkers of atherosclerotic plaque vulnerability and their clinical significance

    Directory of Open Access Journals (Sweden)

    Ran LIU

    2016-09-01

    Full Text Available Inflammatory reaction plays a crucial role in the occurence and development of atherosclerosis. Both basic and clinical trials have provided evidence that the expression of inflammatory biomarkers are closely related with the degree of atherosclerosis. Treatment towards inflammatory factors would bring benefit to atherosclerotic patients. This review highlighted the mechanistic rationale and specific therapies targeting traditional and novel inflammatory biomarkers, including C-reactive protein (CRP, interleukin-17 (IL-17, secretory phospholipase A2 (sPLA2, lipoprotein-associated phospholipase A2 (Lp-PLA2, endoglin, chemokine receptor and 5-lipoxygenase (5-LO, so as to review its mechanism of action and treatment prospect. DOI: 10.3969/j.issn.1672-6731.2016.09.004

  6. Risk assessment of atherosclerotic plaques based on global biomechanics.

    Science.gov (United States)

    Melchionna, Simone; Amati, Giorgio; Bernaschi, Massimo; Bisson, Mauro; Succi, Sauro; Mitsouras, Dimitrios; Rybicki, Frank J

    2013-09-01

    We present the results of a computational study of the entire left coronary system simulated both at Newtonian level and at red blood cell resolution for a sizeable number of physiological conditions. We analyze the cardiovascular implications of stenotic plaques and show that the standard clinical criterion for surgical or percutaneous intervention, based on the fractional flow reserve (FFR), is significantly affected by system-dependent, local hemodynamic factors. A refined version, based on the new notion of local FFR response to stenotic growth, and accounting for statistical uncertainties due to flow heterogeneity, is suggested and illustrated. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

  7. Atherosclerotic plaque targeting mechanism of long-circulating nanoparticles established by multimodal imaging

    DEFF Research Database (Denmark)

    Lobatto, Mark E; Calcagno, Claudia; Millon, Antoine

    2015-01-01

    Atherosclerosis is a major cause of global morbidity and mortality that could benefit from novel targeted therapeutics. Recent studies have shown efficient and local drug delivery with nanoparticles, although the nanoparticle targeting mechanism for atherosclerosis has not yet been fully elucidated....... Here we used in vivo and ex vivo multimodal imaging to examine permeability of the vessel wall and atherosclerotic plaque accumulation of fluorescently labeled liposomal nanoparticles in a rabbit model. We found a strong correlation between permeability as established by in vivo dynamic contrast...... enhanced magnetic resonance imaging and nanoparticle plaque accumulation with subsequent nanoparticle distribution throughout the vessel wall. These key observations will enable the development of nanotherapeutic strategies for atherosclerosis....

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

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

    2013-01-01

    Objectives: Blood pool FDG activity can cloud the atherosclerotic plaque FDG signal. Over time, blood pool FDG activity declines. Therefore, delayed time point FDG PET CT imaging can potentially enhance the assessment of atherosclerotic plaque inflammation. Methods: Twelve healthy volunteers...... without traditional cardiovascular risk factors and three subjects with angina pectoris were prospectively assessed by dual time point 18-FDG PET CT imaging at 90 and 180 minutes after tracer injection. The ratio between aortic SUVmax and the blood pool SUVmean (TBR) was calculated to show the change...... 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 = relationship was observed between aortic cSUV, aging (β = 0.019; t = 2.79; df = 12; P...

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

    Directory of Open Access Journals (Sweden)

    Dolf Segers

    2011-01-01

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

  10. 3D Isotropic MR Culprit Plaque Visualization of Carotid Plaque Edema and Hemorrhage with Motion Sensitized Blood Suppression

    DEFF Research Database (Denmark)

    Søvsø Szocska Hansen, Esben; Pedersen, Steen Fjord; Bloch, Lars Ø.

    2014-01-01

    hemorrhage and plaque edema may represent advanced stages of atherosclerosis[1, 2]. In this study, we present a novel multi-contrast 3D motion sensitized black-blood CMR imaging sequence, which detects both plaque edema and hemorrhage with positive contrast. Subjects and Methods The 3D imaging sequence...... formatting in all three dimensions was possible to provide a comprehensive and exhaustive evaluation of the vessel wall. For the symptomatic carotid artery plaque, hyperintensive signal intensity was detected with a signal-to-noise ratio (SNR) that was significantly higher compared to the vessel wall...... proximal to the bifurcation (43.36±8.01 versus 16.91±3.49, respectively P plaque compared to the proximal carotid vessel wall was 26.45±4.60 and CNR plaque...

  11. The role of selected chemokines and their receptors in the pathogenesis and destabilisation of atheromatous plaques in the carotid arteries

    Directory of Open Access Journals (Sweden)

    Maria Konarska-Król

    2015-04-01

    Full Text Available Chemokines are cytokines that act selectively on cells and are capable of inducing selective migration of cells in vitro and in vivo. The term was first coined at the 3rd International Symposium on Chemotactic Cytokines in 1992. The name “chemokine” is a contraction of “chemotactic cytokine,” meaning that these molecules combine features of both cytokines and chemotactic factors. They are a family of low-molecular-mass proteins acting on specific membrane receptors. A cell’s overall sensitivity to chemotaxis depends on the expression profile of chemokine receptors. Atherosclerosis is essentially an excessive inflammatory and proliferative response to the damage of arterial walls. It takes place within the wall and leads to the formation of unstable atherosclerotic plaques. Many chemokines have been studied in terms of their role in the pathogenesis of an atheromatous plaque in the carotid arteries, both in animal models and with the use of human tissue. It  seems that molecules that are the most involved in the formation of atheromas in the carotid arteries include: CCL2, CCL3, CCL4 and CCL5. However, reports are sometimes contradictory, and more research is needed. Finding a marker that could help predict the destabilisation of an atheromatous plaque would be a valuable addition to the standard diagnostic panel of tests used in both the diagnosis and monitoring of vascular pathologies.

  12. Quantitative colorimetry of atherosclerotic plaque using the L*a*b* color space during angioscopy for the detection of lipid cores underneath thin fibrous caps.

    Science.gov (United States)

    Ishibashi, Fumiyuki; Yokoyama, Shinya; Miyahara, Kengo; Dabreo, Alexandra; Weiss, Eric R; Iafrati, Mark; Takano, Masamichi; Okamatsu, Kentaro; Mizuno, Kyoichi; Waxman, Sergio

    2007-12-01

    Yellow plaques seen during angioscopy are thought to represent lipid cores underneath thin fibrous caps (LCTCs) and may be indicative of vulnerable sites. However, plaque color assessment during angioscopy has been criticized because of its qualitative nature. The purpose of the present study was to test the ability of a quantitative colorimetric system to measure yellow color intensity of atherosclerotic plaques during angioscopy and to characterize the color of LCTCs. Using angioscopy and a quantitative colorimetry system based on the L*a*b* color space [L* describes brightness (-100 to +100), b* describes blue to yellow (-100 to +100)], the optimal conditions for measuring plaque color were determined in three flat standard color samples and five artificial plaque models in cylinder porcine carotid arteries. In 88 human tissue samples, the colorimetric characteristics of LCTCs were then evaluated. In in-vitro samples and ex-vivo plaque models, brightness L* between 40 and 80 was determined to be optimal for acquiring b* values, and the variables unique to angioscopy in color perception did not impact b* values after adjusting for brightness L* by manipulating light or distance. In ex-vivo human tissue samples, b* value >/=23 (35.91 +/- 8.13) with L* between 40 and 80 was associated with LCTCs (fibrous caps <100 mum). Atherosclerotic plaque color can be consistently measured during angioscopy with quantitative colorimetry. High yellow color intensity, determined by this system, was associated with LCTCs. Quantitative colorimetry during angioscopy may be used for detection of LCTCs, which may be markers of vulnerability.

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

    Science.gov (United States)

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

    2016-10-01

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

  14. Atherosclerotic Plaques in the Aortic Arch and Subclinical Cerebrovascular Disease.

    Science.gov (United States)

    Tugcu, Aylin; Jin, Zhezhen; Homma, Shunichi; Elkind, Mitchell S V; Rundek, Tatjana; Yoshita, Mitsuhiro; DeCarli, Charles; Nakanishi, Koki; Shames, Sofia; Wright, Clinton B; Sacco, Ralph L; Di Tullio, Marco R

    2016-11-01

    Aortic arch plaque (AAP) is a risk factor for ischemic stroke, but its association with subclinical cerebrovascular disease is not established. We investigated the association between AAP and subclinical cerebrovascular disease in an elderly stroke-free community-based cohort. The CABL study (Cardiovascular Abnormalities and Brain Lesions) was designed to investigate cardiovascular predictors of silent cerebrovascular disease in the elderly. AAPs were assessed by suprasternal transthoracic echocardiography in 954 participants. Silent brain infarcts and white matter hyperintensity volume (WMHV) were assessed by brain magnetic resonance imaging. The association of AAP thickness with silent brain infarcts and WMHV was evaluated by logistic regression analysis. Mean age was 71.6±9.3 years; 63% were women. AAP was present in 658 (69%) subjects. Silent brain infarcts were detected in 138 participants (14.5%). In multivariate analysis adjusted for potential confounders, AAP thickness and large AAP (≥4 mm in thickness) were significantly associated with the upper quartile of WMHV (WMHV-Q4; odds ratio =1.17; 95% confidence interval, 1.04-1.32; P=0.009 and odds ratio =1.79; 95% confidence interval, 1.40-3.09; P=0.036, respectively), but not with silent brain infarcts (odds ratio =1.08; 95% confidence interval, 0.94-1.23; P=0.265 and odds ratio =1.46; 95% confidence interval, 0.77-2.77; P=0.251, respectively). Aortic arch atherosclerosis was associated with WMHV in a stroke-free community-based elderly cohort. This association was stronger in subjects with large plaques and independent of cardiovascular risk factors. Aortic arch assessment by transthoracic echocardiography may help identify subjects at higher risk of subclinical cerebrovascular disease, who may benefit from aggressive stroke risk factors treatment. © 2016 American Heart Association, Inc.

  15. A computer-simulation study on the effects of MRI voxel dimensions on carotid plaque lipid-core and fibrous cap segmentation and stress modeling.

    Directory of Open Access Journals (Sweden)

    Harm A Nieuwstadt

    Full Text Available 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.In order to provide a methodology that allows such an investigation in detail, numerical simulations of a T1-weighted, contrast-enhanced, 2D MRI sequence were employed. Both the slice thickness (2 mm, 1 mm, and 0.5 mm and the in plane acquired voxel size (0.62x0.62 mm2 and 0.31x0.31 mm2 were varied. This virtual MRI approach was applied to 8 histology-based 3D patient carotid atherosclerotic plaque models.A decreased slice thickness did not result in major improvements in lumen, vessel wall, and lipid-rich necrotic core size measurements. At 0.62x0.62 mm2 in-plane, only a 0.5 mm slice thickness resulted in improved minimum fibrous cap thickness measurements (a 2-3 fold reduction in measurement error and only marginally improved peak cap stress computations. Acquiring voxels of 0.31x0.31 mm2 in-plane, however, led to either similar or significantly larger improvements in plaque component quantification and computed peak cap stress.This study provides evidence that for currently-used 2D carotid MRI protocols, a decreased slice thickness might not be more beneficial for plaque measurement accuracy than a decreased in-plane voxel size. The MRI simulations performed indicate that not a reduced slice thickness (i.e. more isotropic imaging, but the acquisition of anisotropic voxels with a relatively smaller in-plane voxel size could improve carotid plaque quantification and computed peak cap stress accuracy.

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

    Science.gov (United States)

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

    2000-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Leon J Schurgers

    Full Text Available 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.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.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.

  18. Carotid artery plaque and progression of coronary artery calcium: the multi-ethnic study of atherosclerosis.

    Science.gov (United States)

    Polak, Joseph F; Tracy, Russell; Harrington, Anita; Zavodni, Anna E H; O'Leary, Daniel H

    2013-05-01

    Carotid and coronary atherosclerosis are associated with each other in imaging and autopsy studies. The aim of this study was to evaluate whether carotid artery plaque seen on carotid ultrasound can predict incident coronary artery calcification (CAC). Agatston calcium score measurements were repeated in 5,445 participants of the Multi-Ethnic Study of Atherosclerosis (MESA; mean age, 57.9 years; 62.9% women). Internal carotid artery lesions were graded as 0%, 1% to 24%, or >25% diameter narrowing, and intima-media thickness (IMT) was measured. Plaque was present for any stenosis >0%. CAC progression was evaluated with multivariate relative risk regression for CAC scores of 0 at baseline and with multivariate linear regression for CAC score > 0, adjusting for cardiovascular risk factors, body mass index, ethnicity, and common carotid IMT. CAC was positive at baseline in 2,708 of 5,445 participants (49.7%) and became positive in 458 of 2,837 (16.1%) at a mean interval of 2.4 years between repeat examinations. Plaque and internal carotid artery IMT were both strongly associated with the presence of CAC. After statistical adjustment, the presence of carotid artery plaque significantly predicted incident CAC with a relative risk of 1.37 (95% confidence interval, 1.12-1.67). Incident CAC was associated with internal carotid artery IMT, with a relative risk of 1.13 (95% confidence interval, 1.03-1.25) for each 1-mm increase. Progression of CAC was also significantly associated (P < .001) with plaque and internal carotid artery IMT. In individuals free of cardiovascular disease, subjective and quantitative measures of carotid artery plaques by ultrasound imaging are associated with CAC incidence and progression. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

  19. Bayes Clustering and Structural Support Vector Machines for Segmentation of Carotid Artery Plaques in Multicontrast MRI

    Directory of Open Access Journals (Sweden)

    Qiu Guan

    2012-01-01

    Full Text Available Accurate segmentation of carotid artery plaque in MR images is not only a key part but also an essential step for in vivo plaque analysis. Due to the indistinct MR images, it is very difficult to implement the automatic segmentation. Two kinds of classification models, that is, Bayes clustering and SSVM, are introduced in this paper to segment the internal lumen wall of carotid artery. The comparative experimental results show the segmentation performance of SSVM is better than Bayes.

  20. RELATIONSHIPS BETWEEN METABOLIC PARAMETERS AND PLAQUE VULNERABILITY IN THE CAROTID ARTERIES IN PATIENTS WITH DIABETES MELLITUS TYPE 2

    Directory of Open Access Journals (Sweden)

    Muamer Suljić

    2012-09-01

    associated with atherosclerotic changes in the blood vessels. Ultrasound determination of plaque vulnerability in the carotid arteries is one of the most important criteria for the classification of patients at high risk for ischemic stroke and development of DMT2.

  1. The influence of composition and location on the toughness of human atherosclerotic femoral plaque tissue.

    Science.gov (United States)

    Cunnane, E M; Barrett, H E; Kavanagh, E G; Mongrain, R; Walsh, M T

    2016-02-01

    The toughness of femoral atherosclerotic tissue is of pivotal importance to understanding the mechanism of luminal expansion during cutting balloon angioplasty (CBA) in the peripheral vessels. Furthermore, the ability to relate this parameter to plaque composition, pathological inclusions and location within the femoral vessels would allow for the improvement of existing CBA technology and for the stratification of patient treatment based on the predicted fracture response of the plaque tissue to CBA. Such information may lead to a reduction in clinically observed complications, an improvement in trial results and an increased adoption of the CBA technique to reduce vessel trauma and further endovascular treatment uptake. This study characterises the toughness of atherosclerotic plaque extracted from the femoral arteries of ten patients using a lubricated guillotine cutting test to determine the critical energy release rate. This information is related to the location that the plaque section was removed from within the femoral vessels and the composition of the plaque tissue, determined using Fourier Transform InfraRed spectroscopy, to establish the influence of location and composition on the toughness of the plaque tissue. Scanning electron microscopy (SEM) is employed to examine the fracture surfaces of the sections to determine the contribution of tissue morphology to toughness. Toughness results exhibit large inter and intra patient and location variance with values ranging far above and below the toughness of healthy porcine arterial tissue (Range: 1330-3035 for location and 140-4560J/m(2) for patients). No significant difference in mean toughness is observed between patients or location. However, the composition parameter representing the calcified tissue content of the plaque correlates significantly with sample toughness (r=0.949, ptough sections. Regression analysis highlights the potential of employing the calcified tissue content of the plaque as a

  2. 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

    -radical-mediated reaction pathways, which seem to involve mainly the participation of transition- metal ions. We compared the relative abundance of these oxidation products in normal intima, and in human carotid plaque samples with that observed after radiolytically generated hydroxyl radical attack on BSA in vitro......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...

  3. Association Between the Presence of Carotid Artery Plaque and Cardiovascular Events in Patients With Genetic Hypercholesterolemia.

    Science.gov (United States)

    Bea, Ana M; Civeira, Fernando; Jarauta, Estíbaliz; Lamiquiz-Moneo, Itziar; Pérez-Calahorra, Sofía; Marco-Benedí, Victoria; Cenarro, Ana; Mateo-Gallego, Rocío

    2017-07-01

    The equations used in the general population to calculate cardiovascular risk are not useful in genetic hypercholesterolemia (GH). Carotid plaque detection has proved useful in cardiovascular prediction and risk reclassification but there have been no studies of its usefulness in GH. The aim of this study was to determine the association between the presence of carotid artery plaque and the occurrence of cardiovascular events in patients with GH. This study included 1778 persons with GH. The mean follow-up until the occurrence of cardiovascular events was 6.26 years. At presentation, the presence of carotid artery plaque was studied by high-resolution ultrasound. Carotid artery plaque was found in 661 (37.2%) patients: 31.9% with familial hypercholesterolemia, 39.8% with familial combined hyperlipidemia, 45.5% with dysbetalipoproteinemia, and 43.2% with polygenic hypercholesterolemia. During follow-up, 58 patients had a cardiovascular event. Event rates were 6354/100 000 (95%CI, 4432.4-8275.6) in the group with plaque and 1432/100 000 (95%CI, 730.6-2134.3) in the group without plaque, with significant differences between the 2 groups (P < .001). The relative risk of an event was 4.34 (95CI%, 2.44-7.71; P < .001) times higher in patients with plaque and was 2.40 (95%CI, 1.27-4.56; P = .007) times higher after adjustment for major risk factors. The number of carotid artery plaques was positively associated with the risk of cardiovascular events. Most cardiovascular events occur in a subgroup of patients who can be identified by carotid plaque detection. These results support the use of plaque screening in this population and should help in risk stratification and treatment in GH. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  4. Contrast enhancement by differently sized paramagnetic MRI contrast agents in mice with two phenotypes of atherosclerotic plaque

    NARCIS (Netherlands)

    van Bochove, Glenda S.; Paulis, Leonie E. M.; Segers, Dolf; Mulder, Willem J. M.; Krams, Rob; Nicolay, Klaas; Strijkers, Gustav J.

    2011-01-01

    Interest in the use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of three differently sized gadolinium-based contrast agents to permeate different mouse plaque phenotypes was evaluated with MRI. A

  5. Non-calcified coronary atherosclerotic plaque visualization on CT : effects of contrast-enhancement and lipid-content fractions

    NARCIS (Netherlands)

    Kristanto, Wisnumurti; van Ooijen, Peter M. A.; Greuter, Marcel J. W.; Groen, Jaap M.; Vliegenthart, Rozemarijn; Oudkerk, Matthijs

    Computed tomography (CT) may characterize lipid-rich and presumably rupture-prone non-calcified coronary atherosclerotic plaque based on its Hounsfield-Unit (HU), but still inconclusively. This study aimed to evaluate factors influencing the HU-value of non-calcified plaque using software

  6. The association between autonomic dysfunction, inflammation and atherosclerosis in men under investigation for carotid plaques.

    Directory of Open Access Journals (Sweden)

    Marcus A Ulleryd

    Full Text Available Autonomic dysfunction is a risk factor for cardiovascular disease (CVD, however, the exact mechanism linking autonomic dysfunction to cardiovascular disease is not known. In this study we hypothesized that autonomic dysfunction increases inflammation, which subsequently accelerates atherosclerosis. The aim of the current study was to investigate the association between autonomic tone, inflammation and atherosclerosis.124 men under investigation for carotid atherosclerosis were examined for autonomic function (heart rate variability; HRV and baroreflex sensitivity; BRS, inflammatory markers (white blood cell count; WBCC and C-reactive protein; CRP and degree of carotid atherosclerosis. The direct or indirect associations between autonomic function, inflammatory parameters and carotid plaque area were investigated with multiple linear regressions.Male subjects with prevalent CVD showed larger carotid plaque area, higher WBCC, and reduced BRS compared to subjects with no history of CVD. Further, BRS was inversely associated with carotid plaque area (r = -0.21, p = 0.018 as well as inflammatory parameters WBCC and CRP (r = -0.29, p = 0.001, and r = -0.23, p = 0.009, respectively, whereas HRV only was inversely associated with WBCC (r = -0.22, p = 0.014. To investigate if inflammation could provide a link between autonomic function and carotid atherosclerosis we adjusted the associations accordingly. After adjusting for WBCC and CRP the inverse association between BRS and carotid plaque area was attenuated and did not remain significant, while both WBCC and CRP remained significantly associated with carotid plaque area, indicating that low-grade inflammation can possibly link BRS to atherosclerosis. Also, after adjusting for age, antihypertensive treatment and cardiovascular risk factors, BRS was independently inversely associated with both WBCC and CRP, and HRV independently inversely associated with WBCC. WBCC was the only inflammatory marker

  7. 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.

  8. Ultrasound Biomicroscopy for Longitudinal Studies of Carotid Plaque Development in Mice: Validation with Histological Endpoints

    NARCIS (Netherlands)

    Harmon, Erin Y.; Fronhofer, Van; Keller, Rebecca S.; Feustel, Paul J.; Brosnan, M. Julia; von der Thüsen, Jan H.; Loegering, Daniel J.; Lennartz, Michelle R.

    2012-01-01

    Atherosclerosis is responsible for the death of thousands of Americans each year. The carotid constriction model of plaque development has recently been presented as a model for unstable plaque formation in mice. In this study we 1) validate ultrasound biomicroscopy (UBM) for the determination of

  9. Comparison of MRA source image and IVUS for evaluating fibrous cap of carotid plaque

    International Nuclear Information System (INIS)

    Sakamoto, Masahiko; Taoka, Toshiaki; Nakagawa, Hiroyuki; Myochin, Kaoru; Yoshikawa, Kimihiko; Takayama, Katsutoshi; Wada, Takeshi; Iwasaki, Satoru; Fukuzumi, Akio

    2007-01-01

    The purpose is evaluating the usefulness of three-dimensional (3D) time of flight (TOF) MR angiography (MRA) source image for investigating fibrous cap of carotid plaque. The percentage of fibrous cap defect of 17 carotid stenotic lesions was calculated on both MRA source images and intravascular ultrasound (IVUS) images. Five lesions were correlated, but 9 had slight gap (10-20%) and 3 had moderate gap (30-40%). There was significant correlation (P<;0.01, r=0.721) by the Pearson's correlation coefficient. MRA source image can evaluate fibrous cap of carotid plaque. (author)

  10. Protective effect of policosanol on atherosclerotic plaque on aortas in monkeys.

    Science.gov (United States)

    Noa, Miriam; Mas, Rosa

    2005-01-01

    Policosanol is a cholesterol-lowering drug isolated from sugar cane wax with concomitant antiplatelet effects. Previous studies have shown that policosanol prevents lipofundin-induced atherosclerotic lesions in rabbits and rats, including foam cell formation, as well as the development of foam cells in carrageenan-induced granulomas in rats. Policosanol also inhibits smooth muscle cells proliferation induced on rabbit cuffed artery and on forceps-induced arterial wall damage. Furthermore, policosanol administered long term lowered serum cholesterol and prevented the development of atherosclerotic lesions in Macaca arctoides monkeys. The present study was undertaken to determine whether policosanol could change some characteristic features of atherosclerotic lesions, such as macrophage number and immunohistochemical localization of apoA-1 and apoB in aortas of M. arctoides monkeys. Fourteen adult male monkeys weighing 6-10 kg and receiving a low fat, protein-rich diet were randomly distributed in three groups: control group (six monkeys) and two other groups (four monkeys/group) treated with policosanol (2.5 and 25 mg/kg) for 54 weeks. Samples of arteries were examined by light microscopy. Monoclonal antibodies were used to evaluate the presence of macrophage, apoA-1 and apoB. Policosanol reduced the presence of macrophages and the occurrence of apoB, whereas increased apoA-1 localization in aortic atherosclerotic lesions compared with control monkeys. These results suggest the policosanol potential benefit on plaque composition and stability and could explain the protective effects of policosanol on atherosclerosis development.

  11. Carotid Artery Stenting Successfully Prevents Progressive Stroke Due to Mobile Plaque

    Directory of Open Access Journals (Sweden)

    Masahiro Oomura

    2015-05-01

    Full Text Available We report a case of progressive ischemic stroke due to a mobile plaque, in which carotid artery stenting successfully prevented further infarctions. A 78-year-old man developed acute multiple infarcts in the right hemisphere, and a duplex ultrasound showed a mobile plaque involving the bifurcation of the left common carotid artery. Maximal medical therapy failed to prevent further infarcts, and the number of infarcts increased with his neurological deterioration. Our present case suggests that the deployment of a closed-cell stent is effective to prevent the progression of the ischemic stroke due to the mobile plaque.

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

    Directory of Open Access Journals (Sweden)

    Abigail S Haka

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

  13. Temperature distribution in atherosclerotic coronary arteries: influence of plaque geometry and flow (a numerical study)

    International Nuclear Information System (INIS)

    Have, A G ten; Gijsen, F J H; Wentzel, J J; Slager, C J; Steen, A F W van der

    2004-01-01

    Intravascular coronary thermography is a method that may detect vulnerable, atherosclerotic plaques and is currently evaluated in a clinical setting. Active macrophages or enzymatic heat releasing processes in vulnerable plaques may act as heat sources. To better understand the parameters of influence on thermographic measurements, numerical simulations have been performed on a model of a coronary artery segment containing a heat source. Heat source parameters and flow were varied to study their influence on temperatures at the lumen wall. Maximal temperature differences at the lumen wall increased when the source volume increased and they differ with the source geometry. The simulations showed that blood flow acts as a coolant to the lumen wall. Blood flow decreased maximal temperatures depending on the source geometry, source volume and the maximal flow velocity. Influence of flow was highest for circumferentially extended sources, up to a factor 3.7, and lowest for longitudinally extended sources, down to a factor 1.9. When cap thickness increased, maximal temperatures decreased and the influence of flow increased. This study shows that correct interpretation of intravascular thermographic measurements requires data on the flow and on the morphologic characteristics of the atherosclerotic plaque

  14. Antioxidants attenuate atherosclerotic plaque development in a balloon-denuded and -radiated hypercholesterolemic rabbit

    International Nuclear Information System (INIS)

    Leborgne, Laurent; Fournadjiev, Jana; Pakala, Rajbabu; Dilcher, Christian; Cheneau, Edouard; Wolfram, Roswitha; Hellinga, David; Seaborn, Rufus; O'Tio, Fermin; Waksman, Ron

    2003-01-01

    Background: Oxidation of lipoproteins is considered to be a key contributor to atherogenesis. Antioxidants are potential antiatherogenic agents because they can inhibit lipoprotein oxidation. Radiation has been shown to increase oxidative stress leading to increased atherogenesis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and -radiated rabbits. Methods and Results: Two groups of New Zealand white rabbits (n=36) were fed with 1% cholesterol diet (control diet) or with 1% cholesterol diet containing a mixture of various antioxidants for 1 week. Iliac arteries in all the animals were balloon denuded and continued to fed with 0.15% cholesterol diet or 0.15% cholesterol diet containing antioxidants (antioxidant diet). Four weeks after balloon denudation one iliac artery in 12 animals from each group was radiated and all the animals were continued to be fed with the same diet. Four weeks after radiation animals were sacrificed and morphometric analysis of iliac arteries (n=12) in nonradiated and radiated animals were performed. Plaque area (PA) in the rabbits that were fed with cholesterol diet is 0.2±0.12 mm 2 , and it is increased by 2.75-fold (P<.05) in the radiated arteries of animals fed with cholesterol diet. Plaque area in the animals fed with antioxidant diet is 50% less then the one in the animals fed with cholesterol diet. Similarly, plaque area in radiated arteries of the animals fed with antioxidant diet is 50% less then the animals fed with cholesterol diet. Conclusion: Antioxidants significantly attenuate atherosclerotic plaque progression in balloon-injured and -radiated hypercholesterolemic rabbits

  15. Enterprise stent in recanalizing non-acute atherosclerotic intracranial internal carotid artery occlusion.

    Science.gov (United States)

    Wang, Xiaofei; Wang, Zhigang; Ji, Yong; Ding, Xuan; Zang, Yizheng; Wang, Chengwei

    2017-11-01

    To investigate the safety and effectiveness of recanalization in non-acute occlusion of intracranial internal carotid arteries using the flexible Enterprise self-expanding stent. From June 2014 to June 2016, 12 consecutive patients with non-acute occlusion of intracranial internal carotid arteries received endovascular recanalization with Enterprise stenting. All patients received medication for anti-platelet aggregation therapy before and after the operation. The perioperative complications and recanalization efficacy were evaluated with the modified Rankin scoring system and digital subtraction angiography (DSA) follow-up, respectively. Endovascular recanalization was successfully performed in 10 out of 12 patients with Enterprise stenting. Stent implantation following balloon dilatation failed in one patient because the lumen diameter was too small. Another recanalization failed because the guide wire could not pass through the occlusion. No perioperative mortality was observed. One case of acute thrombosis and one case of intraoperative carotid spasm occurred, but these were resolved with thrombolytic therapy by microcatheter exposure treatment and antispasmodic medications, respectively. DSA follow-up in seven patients revealed no re-occlusion. One stroke event occurred in the 10 patients who completed the follow-up. A meaningful improvement in the modified Rankin score during follow-up was suggested by Wilcoxon signed-rank test results. The Enterprise stent was shown to be safe and efficient in recanalizing non-acute atherosclerotic intracranial internal carotid artery occlusion. However, the long-term outcomes need to be further investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Automatic classification of atherosclerotic plaques imaged with intravascular OCT (Conference Presentation)

    Science.gov (United States)

    Rico-Jimenez, Jose D.; Campos-Delgado, Daniel U.; Villiger, Martin; Bouma, Brett; Jo, Javier A.

    2016-03-01

    A novel computational method for plaque tissue characterization based on Intravascular Optical Coherence Tomography (IV-OCT) is presented. IV-OCT is becoming a powerful tool for the clinical evaluation of atherosclerotic plaques; however, it requires a trained expert for visual assessment and interpretation of the imaged plaques. Moreover, due to the inherit effect of speckle and the scattering attenuation of the optical scheme the direct interpretation of OCT images is limited. To overcome these difficulties, we propose to automatically identify the A-line profiles of the most significant plaque types (normal, fibrotic, or lipid-rich) and their respective abundance by using a probabilistic framework and blind alternated least squares to achieve the optimal decomposition. In this context, we present preliminary results of this novel probabilistic classification tool for intravascular OCT that relies on two steps. First, the B-scan is pre-processed to remove catheter artifacts, segment the lumen, select the region of interest (ROI), flatten the tissue surface, and reduce the speckle effect by a spatial entropy filter. Next, the resulting image is decomposed and its A-lines are classified by an automated strategy based on alternating-least-squares optimization. Our early results are encouraging and suggest that the proposed methodology can identify normal tissue, fibrotic and lipid-rich plaques from IV-OCT images.

  17. Imaging of hypoxia in mouse atherosclerotic plaques with 64Cu-ATSM

    International Nuclear Information System (INIS)

    Nie, Xingyu; Randolph, Gwendalyn J.; Elvington, Andrew; Bandara, Nilantha; Zheleznyak, Alexander; Gropler, Robert J.; Woodard, Pamela K.; Lapi, Suzanne E.

    2016-01-01

    Introduction: Cardiovascular disease is the leading cause of death in the United States. The identification of vulnerable plaque at risk of rupture has been a major focus of research. Hypoxia has been identified as a potential factor in the formation of vulnerable plaque, and it is clear that decreased oxygen plays a role in the development of plaque angiogenesis leading to plaque destabilization. The purpose of this study is to demonstrate the feasibility of copper-64 labeled diacetyl-bis (N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), a positron-emitting radiopharmaceutical taken up in low-oxygen-tension cells, for the identification of hypoxic and potentially unstable atherosclerotic plaque in a mouse model. Methods: 64 Cu-ATSM PET was performed in 21 atherosclerotic apolipoprotein E knockout (ApoE −/− ) mice, 6 of which were fed high-fat diet (HFD) while the others received standard-chow diet (SCD), and 13 control wild type mice fed SCD. 4 SCD ApoE −/− mice and 4 SCD wild type mice also underwent 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) imaging one day prior to 64 Cu-ATSM PET. Results: 64 Cu-ATSM uptake was increased in the aortic arch in SCD ApoE −/− mice (average aortic arch/muscle (A/M) standardized uptake value ratio 7.5–30 min post injection: (5.66 ± 0.23) compared to control mice (A/M SUV ratio 7.5–30 min post injection (3.87 ± 0.22), p < 0.0001). HFD ApoE −/− mice also showed similarly increased aortic arch uptake on PET imaging in comparison to control mice. Immunohistochemistry in both HFD and SCD ApoE −/− mice revealed noticeable hypoxia by pimonidazole stain in atherosclerosis which was co-localized to macrophage by CD68 staining. Autoradiography assessment demonstrated the presence of hypoxia by 64 Cu-ATSM uptake correlated with pimonidazole uptake within the ex vivo atherosclerotic aortic arch specimens. A significant increase in 18 F-FDG uptake in the SCD ApoE −/− mice in comparison to

  18. 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, Moustapha

    2007-01-01

    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......BACKGROUND: Signs of preceding episodes of plaque rupture and smooth muscle cell (SMC)-mediated healing are common in atherosclerotic plaques, but the source of the healing SMCs is unknown. Recent studies suggest that activated platelets adhering to sites of injury recruit neointimal SMCs from...... 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...

  19. 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

  20. Association of paraoxonase 1 gene polymorphism and enzyme activity with carotid plaque in rheumatoid arthritis.

    Science.gov (United States)

    Charles-Schoeman, Christina; Lee, Yuen Yin; Shahbazian, Ani; Gorn, Alan H; Fitzgerald, John; Ranganath, Veena K; Taylor, Mihaela; Ragavendra, Nagesh; McMahon, Maureen; Elashoff, David; Reddy, Srinivasa T

    2013-11-01

    To investigate the relationship of genetic and biochemical determinants of paraoxonase 1 activity to carotid plaque as a surrogate marker of cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). The relationships between paraoxonase 1 activity, PON1 genotype (for the functional polymorphism at position 192), and carotid plaque presence were determined in 168 RA patients. After an overnight fast, blood was collected for lipoprotein analysis, and paraoxonase 1 activity was measured using paraoxon as the substrate. The PON1 Q192R genotype was determined for all patients. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease characteristics were assessed for all patients. Paraoxonase 1 activity values in the RA patients were highest for the RR genotype, intermediate for the QR genotype, and lowest for the QQ genotype (P paraoxonase 1 activity with carotid plaque in RA patients. Lower plasma paraoxonase 1 activity was associated with increased risk of carotid plaque (P paraoxonase 1 to CV risk in RA patients, as assessed by the presence or absence of carotid plaque. Further CV outcome studies are warranted to validate the utility of paraoxonase 1 as a biomarker of CV risk in patients with RA. Copyright © 2013 by the American College of Rheumatology.

  1. Carotid plaque is a new risk factor for peripheral vestibular disorder: a retrospective cohort study.

    Science.gov (United States)

    Wada, Masaoki; Takeshima, Taro; Nakamura, Yosikazu; Nagasaka, Shoichiro; Kamesaki, Toyomi; Kajii, Eiji

    2016-08-01

    Many chronic diseases are associated with dizziness or vertigo, as is peripheral vestibular disorder (PVD). Although carotid plaque development is linked to atherosclerosis, it is unclear whether such plaques can lead to the development of PVD. We therefore conducted this study to investigate the presence of an association between carotid plaque and new PVD events.In this retrospective study, we consecutively enrolled 393 patients ≥20 years old who had been treated for chronic diseases such as hypertension, dyslipidemia, and diabetes mellitus for ≥6 months at a primary care clinic (Oki Clinic, Japan) between November 2011 and March 2013. Carotid plaque presence was measured with high-resolution ultrasonography for all patients. During a 1-year follow-up period, an otorhinolaryngologist diagnosed and reported any new PVD events (the main end point). Hazard ratios (HRs) and 95% confidence intervals (CIs) for new PVD occurrence were estimated using the Cox proportional hazard regression model.The mean age of the participants was 65.5 years; 33.8% were men, and 12.7%, 82.4%, and 93.1% had diabetes mellitus, hypertension, and dyslipidemia, respectively. There were 76 new PVD events; patients with carotid plaque had a greater risk of such events (crude HR: 3.25; 95% CI: 1.62-6.52) compared to those without carotid plaque. This risk was even higher after adjusting for traditional risk factors for atherosclerosis (adjusted HR: 4.41; 95% CI: 1.75-11.14).Carotid plaques are associated with an increased risk of new PVD events.

  2. ULTRASONIC DETERMINATION OF PLAQUE VULNERABILITY IN CAROTID ARTERIES AND CORRELATION WITH VISCERAL FAT THICKNESS IN PATIENTS WITH DIABETES MELLITUS TYPE 2

    Directory of Open Access Journals (Sweden)

    Muamer Suljić

    2009-12-01

    Full Text Available The basic pathohistological substrate of vascular complications is atherosclerotic plaque and, therefore, the adequate treatment of patients with vascular disease is conditioned by timely and precise diagnosis. The introduction of ultrasound technology in clinical practice was enabled by Edler and Hertz in 1954, when they presented the myocardial motions, then by Yoshida in 1956, Sotomura in 1959, and Frenklin in 1961, who used ultrasound to display the blood flow in the human blood vessels. The aim of our study was to determine the incidence and vulnerability of plaques in the carotid arteries and to examine the association between plaque vulnerability and visceral fat thickness in patients with diabetes mellitus type 2. The investigation involved 82 subjects divided into two groups. The first group included 51 subjects suffering from diabetes mellitus type 2, while the second group involved 31 healthy controls. Among the examinees, a significantly higher incidence of plaque vulnerability was reported in the patients suffering from diabetes melitus type 2. Average thickness of intraabdominal fatty tissue was significantly higher in the patients with diabetes mellitus type 2 compared to controls. The incidence of vulnerable plaques significantly correlated with diabetes mellitus incidence and thickness of intraabdominal fatty tissue. Visceral obesity and diabetes mellitus type 2 showed significant association with atherosclerosis. Ultrasound determination of carotid stenosis and intraabdominal fatty tissue thickness are the most important criteria for classification of patients with high risk of ischemic stroke.

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

    Science.gov (United States)

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

    2018-01-06

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

  4. Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice.

    Science.gov (United States)

    Oh, Yun K; Bachar, Adi R; Zacharias, David G; Kim, Sung Gyun; Wan, Junxiang; Cobb, Laura J; Lerman, Lilach O; Cohen, Pinchas; Lerman, Amir

    2011-11-01

    Humanin (HN) is a cytoprotective peptide derived from endogenous mitochondria, expressed in the endothelial layer of human vessels, but its role in atherogenesis in vivo is not known. In vitro study, however, HN reduced oxidized low-density lipoprotein induced formation of reactive oxygen species and apoptosis. The present study tested the hypothesis that long term treatment with HN will have a protective role against endothelial dysfunction and progression of atherosclerosis in vivo. Daily intraperitonial injection of the HN analogue HNGF6A for 16 weeks prevented endothelial dysfunction and decreased atherosclerotic plaque size in the proximal aorta of ApoE-deficient mice fed on a high cholesterol diet, without showing direct vasoactive effects or cholesterol-reducing effects. HN was expressed in the endothelial layer on the aortic plaques. HNGF6A treatment reduced apoptosis and nitrotyrosine immunoreactivity in the aortic plaques without affecting the systemic cytokine profile. HNGF6A also preserved expression of endothelial nitric oxide synthase in aorta. HN may have a protective effect on endothelial function and progression of atherosclerosis by modulating oxidative stress and apoptosis in the developing plaque. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Intraplaque Hemorrhage and the Plaque Surface in Carotid Atherosclerosis: The Plaque At RISK Study (PARISK)

    NARCIS (Netherlands)

    van Dijk, A. C.; Truijman, M. T. B.; Hussain, B.; Zadi, T.; Saiedie, G.; de Rotte, A. A. J.; Liem, M. I.; van der Steen, A. F. W.; Daemen, M. J. A. P.; Koudstaal, P. J.; Nederkoorn, P. J.; Hendrikse, J.; Kooi, M. E.; van der Lugt, A.

    2015-01-01

    An important characteristic of vulnerable plaque, intraplaque hemorrhage, may predict plaque rupture. Plaque rupture can be visible on noninvasive imaging as a disruption of the plaque surface. We investigated the association between intraplaque hemorrhage and disruption of the plaque surface. We

  6. Improved Correlation of Strain Indices with Cognitive Dysfunction with Inclusion of Adventitial Layer with Carotid Plaque.

    Science.gov (United States)

    Wang, X; Mitchell, C C; Varghese, T; Jackson, D C; Rocque, B G; Hermann, B P; Dempsey, R J

    2016-05-01

    Plaque instability may lead to chronic embolization, which in turn may contribute to progressive cognitive decline. Accumulated strain tensor indices over a cardiac cycle within a pulsating carotid plaque may be viable biomarkers for the diagnosis of plaque instability. Using plaque-only carotid artery segmentations, we recently demonstrated that impaired cognitive function correlated significantly with maximum axial and lateral strain indices within a localized region of interest in plaque. Inclusion of the adventitial layer focuses our strain or instability measures on the vessel wall-plaque interface hypothesized to be a region with increased shearing forces and measureable instability. A hierarchical block-matching motion tracking algorithm developed in our laboratory was used to estimate accumulated axial, lateral, and shear strain distribution in plaques identified with the plaque-with-adventitia segmentation. Correlations of strain indices to the Repeatable Battery for the Assessment of Neuropsychological Status Total score were performed and compared with previous results. Overall, correlation coefficients (r) and significance (p) values improved for axial, lateral, and shear strain indices. Shear strain indices, however, demonstrated the largest improvement. The Pearson correlation coefficients for maximum shear strain and cognition improved from the previous plaque-only analyses of -0.432 and -0.345 to -0.795 and -0.717 with the plaque-with-adventitia segmentation for the symptomatic group and for all patients combined, respectively. Our results demonstrate the advantage of including adventitia for ultrasound carotid strain imaging providing improved association to parameters assessing cognitive impairment in patients. This supports theories of the importance of the vessel wall plaque interface in the pathophysiology of embolic disease. © The Author(s) 2015.

  7. Lipid discordance and carotid plaque in obese patients in primary prevention.

    Science.gov (United States)

    Masson, Walter; Siniawski, Daniel; Lobo, Martín; Molinero, Graciela

    2018-01-01

    Obese patients with lipid discordance (non-HDL cholesterol levels 30mg/dL above the LDL-c value) may have a greater prevalence of carotid atherosclerotic plaque (CAP). Our study objectives were: 1) To assess the prevalence of lipid discordance in a primary prevention population of obese patients; 2) To investigate the association between lipid discordance and presence of CAP. Obese subjects aged >18 years (BMI ≥30kg/m 2 ) with no cardiovascular disease, diabetes, or lipid-lowering treatment from six cardiology centers were included. Lipid discordance was defined when, regardless of the LDL-c level, the non-HDL cholesterol value exceeded the LDL-c value by 30mg/dL. Presence of CAP was identified by ultrasonography. Univariate and multivariate analyses were performed to explore the association between lipid discordance and presence of CAP. The study simple consisted of 325 obese patients (57.2% men; mean age, 52.3 years). Prevalence of lipid discordance was 57.9%. CAP was found in 38.6% of patients, but the proportion was higher in subjects with lipid discordance as compared to those without this lipid pattern (44.4% vs. 30.7%, P=.01). In both the univariate (OR: 1.80; 95% CI: 1.14-2.87; P=.01) and the multivariate analysis (OR: 2.07; 95% CI: 1.22-3.54; P=.007), presence of lipid discordance was associated to an increased probability of CAP. In these obese patients, lipid discordance was associated to greater prevalence of CAP. Evaluation of obese patients with this strategy could help identify subjects with higher residual cardiovascular risk. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Risk factors associated with the carotid intima-media thickness and plaques: ESPREDIA Study.

    Science.gov (United States)

    Mostaza, Jose M; Lahoz, Carlos; Salinero-Fort, Miguel A; Laguna, Fernando; Estirado, Eva; García-Iglesias, Francisca; González Alegre, Teresa; Sabín, Concesa; López, Silvia; Cornejo, Victor

    2017-09-19

    To evaluate whether there were any differences in the risk factor profile associated with either the intima-media thickness (IMT) or the presence of carotid plaques. Cross-sectional study in 1475 subjects between 45 and 75years, randomly selected from the population of the Northwest area of Madrid (Spain). They had a physical exam, blood analysis, and ultrasound measurement of the IMT and of the presence of plaques. Mean IMT was 0.725±0.132mm. Forty seven percent of the participants had carotid plaques. In multivariate analysis, factors directly associated with the IMT were, age (β0.227, PFactors associated with the IMT and the presence of plaques are similar, a finding that support a continuum between muscular layer hypertrophy and arteriosclerosis development. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Measurement of fibrous cap thickness in atherosclerotic plaques by spatiotemporal analysis of laser speckle images

    Science.gov (United States)

    Nadkarni, Seemantini K.; Bilenca, Alberto; Bouma, Brett E.; Tearney, Guillermo J.

    2010-01-01

    Necrotic-core fibroatheromas (NCFA) with thin, mechanically weak fibrous caps overlying lipid cores comprise the majority of plaques that rupture and cause acute myocardial infarction. Laser speckle imaging (LSI) has been recently demonstrated to enable atherosclerotic plaque characterization with high accuracy. We investigate spatio-temporal analysis of LSI data, in conjunction with diffusion theory and Monte Carlo modeling of light transport, to estimate fibrous cap thickness in NCFAs. Time-varying laser speckle images of 20 NCFAs are selected for analysis. Spatio-temporal intensity fluctuations are analyzed by exponential fitting of the windowed normalized cross-correlation of sequential laser speckle patterns to obtain the speckle decorrelation time constant, τ(ρ), as a function of distance ρ from the source entry location. The distance, ρ′, at which τ(ρ) dropped to 65% of its maximum value is recorded. Diffusion theory and Monte Carlo models are utilized to estimate the maximum photon penetration depth, zmax(ρ′), for a distance equal to ρ′, measured from LSI. Measurements of zmax(ρ′) correlate well with histological measurements of fibrous cap thickness (R=0.78, p<0.0001), and paired t-tests show no significant difference between the groups (p=0.4). These results demonstrate that spatio-temporal LSI may allow the estimation of fibrous cap thickness in NCFAs, which is an important predictor of plaque Stability. PMID:16674181

  10. Non-invasive Carotid Artery Imaging to Identify the Vulnerable Plaque: Current Status and Future Goals.

    Science.gov (United States)

    Huibers, A; de Borst, G J; Wan, S; Kennedy, F; Giannopoulos, A; Moll, F L; Richards, T

    2015-11-01

    The current clinical practise to determine if a patient should undergo carotid intervention to prevent stroke is to determine the clinical features combined with degree of carotid stenosis. However, this does not accurately determine the individual patient's risk for future stroke. A thin fibrous cap, a large lipid core, high macrophage count, and intraplaque haemorrhage have all been identified as markers of the so-called "vulnerable" plaque being related to a higher stroke risk. There is a need to assess the accuracy of in vivo imaging to identify vulnerable plaque characteristics, thereby enabling in vivo risk stratification to guide clinical decision-making. The aim of this topical review is to assess the roles of currently available imaging modalities that are applied in clinical practice and those experimental techniques that are close to clinical translation in defining carotid plaque characteristics and in informing clinical practice. Ultrasound is a low cost and ready available low-risk tool, but it lacks the accuracy to reliably detect individual plaque components and characteristics. Computed tomography is considered to be the best imaging technique to identify calcification in the carotid plaque. Magnetic resonance imaging (MRI) can identify most described plaque characteristics with moderate to good agreement. Positron emission tomography allows assessment of specific metabolic functions with tracers labelled with positron emitting radio-isotopes, but limited spatial resolution makes anatomic precision imprecise. MRI has demonstrated the most potential, with good sensitivity and specificity for most plaque characteristics. However, currently there is no single imaging modality that can reliably identify the vulnerable plaque in relation to development of future stroke. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  11. 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.

  12. Differences in atherosclerotic plaque burden and morphology between type 1 and 2 diabetes as assessed by multislice computed tomography

    NARCIS (Netherlands)

    Djaberi, Roxana; Schuijf, Joanne D.; Boersma, Eric; Kroft, Lucia J. M.; Pereira, Alberto M.; Romijn, Johannes A.; Scholte, Arthur J.; Jukema, J. Wouter; Bax, Jeroen J.

    2009-01-01

    OBJECTIVE It is unclear whether the coronary atherosclerotic plaque burden is similar in patients with type 1 and type 2 diabetes. By using multislice computed tomography (MSCT), the presence, degree, and morphology of coronary artery disease (CAD) in patients with type 1 and type 2 diabetes were

  13. The impact of intermittent and repetitive cold stress exposure on endoplasmic reticulum stress and instability of atherosclerotic plaques.

    Science.gov (United States)

    Dai, Ming-Xiang; Zheng, Xiao-Hui; Yu, Jin; Yin, Tao; Ma, Mei-Juan; Zhang, Le; Liu, Min; Ma, Ying; Liu, Li-Wen; Gao, Xue; Li, Yan; Song, Li-Qiang; Wang, Hai-Chang

    2014-01-01

    The incidence of acute coronary syndrome caused by the rupture of atherosclerotic plaque and subsequent arterial thrombosis increases as the weather gets colder. However, the association between cold stress and atherosclerotic plaque rupture is currently unknown. An atherosclerotic plaque model was established in rabbits by balloon injury and a high-fat diet with or without cold stress (4 °C, 1 hour per day, 20 weeks) at the onset of modeling. Additionally, oxidized low-density lipoprotein (ox-LDL) was applied to induce the formation of macrophage foam cells in vitro. Serum lipid profiles and inflammatory cytokines (ox-LDL, high-sensitivity C-reactive protein, and interleukin-8) were significantly higher in cold stress-exposed rabbits than in controls (Pinstability of atherosclerotic plaques through activating ERS and enhancing cell apoptosis. Up-regulated CHOP levels mediated by PERK and ATF6 and the activated IRE1-XBP1-JNK pathway contributed to the apoptosis of foam cells. © 2014 S. Karger AG, Basel.

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

    Directory of Open Access Journals (Sweden)

    Ming-Xiang Dai

    2014-07-01

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

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

    NARCIS (Netherlands)

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

    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

  16. 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

    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...

  17. Altered carotid plaque signal among different repetition times on T1-weighted magnetic resonance plaque imaging with self-navigated radial-scan technique

    International Nuclear Information System (INIS)

    Narumi, Shinsuke; Ohba, Hideki; Mori, Kiyofumi; Ohura, Kazumasa; Ono, Ayumi; Terayama, Yasuo; Sasaki, Makoto; Ogasawara, Kuniaki; Hitomi, Jiro

    2010-01-01

    Magnetic resonance (MR) plaque imaging for carotid arteries is usually performed by using an electrocardiograph (ECG)-gating technique to eliminate pulsation-related artifacts, which can affect the plaque signals because of varied repetition time (TR) among patients. Hence, we investigated whether differences in TR causes signal alterations of the carotid plaque by using a non-gated plaque imaging technique. We prospectively examined 19 patients with carotid stenosis by using a T1-weighted self-navigated radial-scan technique with TRs of 500, 700, and 900 ms. The signal intensity of the carotid plaque was measured, and the contrast ratio (CR) relative to the adjacent muscle was calculated. CRs of the carotid plaques were 1.39 ± 0.39, 1.29 ± 0.29, and 1.23 ± 0.24 with TRs of 500, 700, and 900 ms, respectively, and were significantly different. Among the plaques, those with a hyperintensity signal (CR > 1.5) and moderate-intensity signal (CR 1.2-1.5) at 500 ms showed a TR-dependent signal decrease (hyperintensity plaques, 1.82 ± 0.26; 1.61 ± 0.19; and 1.48 ± 0.17; moderate-intensity plaques, 1.33 ± 0.08; 1.26 ± 0.08; and 1.19 ± 0.07), while those with an isointensity signal (CR < 1.2) remained unchanged regardless of TR (0.96 ± 0.12, 0.96 ± 0.11, and 0.97 ± 0.13). The signal intensity of the carotid plaque on T1-weighted imaging significantly varies among different TRs and tends to decrease with longer TR. MR plaque imaging with short and constant TR settings that the ECG-gating method cannot realize would be preferable for evaluating plaque characteristics. (orig.)

  18. Altered carotid plaque signal among different repetition times on T1-weighted magnetic resonance plaque imaging with self-navigated radial-scan technique

    Energy Technology Data Exchange (ETDEWEB)

    Narumi, Shinsuke; Ohba, Hideki; Mori, Kiyofumi; Ohura, Kazumasa; Ono, Ayumi; Terayama, Yasuo [Iwate Medical University, Department of Neurology and Gerontology, Morioka (Japan); Sasaki, Makoto [Iwate Medical University, Advanced Medical Research Center, Morioka (Japan); Ogasawara, Kuniaki [Iwate Medical University, Department of Neurosurgery, Morioka (Japan); Hitomi, Jiro [Iwate Medical University, Department of Anatomy, Morioka (Japan)

    2010-04-15

    Magnetic resonance (MR) plaque imaging for carotid arteries is usually performed by using an electrocardiograph (ECG)-gating technique to eliminate pulsation-related artifacts, which can affect the plaque signals because of varied repetition time (TR) among patients. Hence, we investigated whether differences in TR causes signal alterations of the carotid plaque by using a non-gated plaque imaging technique. We prospectively examined 19 patients with carotid stenosis by using a T1-weighted self-navigated radial-scan technique with TRs of 500, 700, and 900 ms. The signal intensity of the carotid plaque was measured, and the contrast ratio (CR) relative to the adjacent muscle was calculated. CRs of the carotid plaques were 1.39 {+-} 0.39, 1.29 {+-} 0.29, and 1.23 {+-} 0.24 with TRs of 500, 700, and 900 ms, respectively, and were significantly different. Among the plaques, those with a hyperintensity signal (CR > 1.5) and moderate-intensity signal (CR 1.2-1.5) at 500 ms showed a TR-dependent signal decrease (hyperintensity plaques, 1.82 {+-} 0.26; 1.61 {+-} 0.19; and 1.48 {+-} 0.17; moderate-intensity plaques, 1.33 {+-} 0.08; 1.26 {+-} 0.08; and 1.19 {+-} 0.07), while those with an isointensity signal (CR < 1.2) remained unchanged regardless of TR (0.96 {+-} 0.12, 0.96 {+-} 0.11, and 0.97 {+-} 0.13). The signal intensity of the carotid plaque on T1-weighted imaging significantly varies among different TRs and tends to decrease with longer TR. MR plaque imaging with short and constant TR settings that the ECG-gating method cannot realize would be preferable for evaluating plaque characteristics. (orig.)

  19. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial.

    Science.gov (United States)

    Joshi, Nikhil V; Vesey, Alex T; Williams, Michelle C; Shah, Anoop S V; Calvert, Patrick A; Craighead, Felicity H M; Yeoh, Su Ern; Wallace, William; Salter, Donald; Fletcher, Alison M; van Beek, Edwin J R; Flapan, Andrew D; Uren, Neal G; Behan, Miles W H; Cruden, Nicholas L M; Mills, Nicholas L; Fox, Keith A A; Rudd, James H F; Dweck, Marc R; Newby, David E

    2014-02-22

    The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG). In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction. In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], pcoronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21

  20. Impact of Wall Shear Stress and Pressure Variation on the Stability of Atherosclerotic Plaque

    Science.gov (United States)

    Taviani, V.; Li, Z. Y.; Sutcliffe, M.; Gillard, J.

    Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady and unsteady conditions assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding one dimensional models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed linearly elastic, homogeneous isotropic. The analysis showed that wall shear stress is small (less than 3.5%) with respect to pressure drop throughout the cycle even for severe stenosis. On the contrary, the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by one dimensional models. This suggests that the primary source of mistakes in one dimensional studies comes from neglecting the three dimensional geometry of the plaque. Neglecting axial forces only involves minor errors.

  1. Human carotid plaque phosphatidylcholine specifically interacts with paraoxonase 1, increases its activity, and enhances its uptake by macrophage at the expense of its binding to HDL.

    Science.gov (United States)

    Cohen, Elad; Aviram, Michael; Khatib, Soliman; Artoul, Fadi; Rabin, Asaf; Mannheim, Dalit; Karmeli, Ron; Salamon, Tal; Vaya, Jacob

    2014-11-01

    Human carotid atherosclerotic plaque is in direct contact with circulatory blood components. Thus, plaque and blood components may affect each other. The current study presents the effects of plaque chloroform:methanol (C:M) extract on the HDL-associated enzyme paraoxnase 1 (PON1). This study is part of our investigation on the mutual effects of the interactions between atherosclerotic lesions and blood components. Recombinant PON1 (rePON1) was incubated with the human carotid plaques C:M extract and PON1 activities were analyzed. Lactonase and paraoxonase activities were elevated due to C:M treatment, by 140 and by 69%, respectively. Analytical chemistry analyses revealed specific phosphatidylcholines (PCs) as the plaque active components. Tryptophan fluorescence quenching assay, together with molecular docking, shows that PON1 activity is enhanced in correlation with the level of PC affinity to PON1. Molecular docking revealed that PCs interact specifically with H2-PON1 α-helix, which together with H1 enzyme α-helix links the protein to the HDL surface. These findings are supported by additional results from the PON1 ∆20 mutant that lack its H1-α-helix. Incubation of this mutant with the plaque C:M extract increased PON1 activity by only 20%, much less than the wild-type PON1 that elevated PON1 activity at the same concentration by as much as 95%. Furthermore, as much as the affinity of the enzyme to the PC was augmented, the ability of PON1 to bind to the HDL particle decreased. Finally, PON1 interaction with PC enhance its uptake into the macrophage cytoplasm. In conclusions, Specific lesion phosphatidylcholines (PCs) present in the human carotid plaque significantly enhance PON1 catalytic activities due to their interaction with the enzyme. Such a lesion׳s PC-PON1 interaction, in turn, competes with HDL PCs and enhances PON1 uptake by macrophage at the expense of PON1 binding to the HDL. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Three-Dimensional and Conventional Carotid Ultrasound for Assessment of Carotid Plaque in a Stroke Patient: A Simple Way to Validate Findings.

    Science.gov (United States)

    Kalashyan, Hayrapet; Saqqur, Maher; Becher, Harald; O'Kelly, Cian; Romanchuk, Helen; Khan, Khurshid; Jeerakathil, Thomas; Wassef, Andrew; Shuaib, Ashfaq

    2017-03-01

    Single-sweep automated 3-D ultrasound is a new imaging modality for the assessment of carotid plaque. Its most important application is the measurement of the plaque volume. To our knowledge, to date there is not a widely accepted "gold standard" to validate 3-D plaque volume measurement. We compared the findings of 2-dimensional and 3-D carotid ultrasound imaging with those of postsurgical plaque specimen using a simple method. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  3. [18F]FDG Uptake in the Aortic Wall Smooth Muscle of Atherosclerotic Plaques in the Simian Atherosclerosis Model

    Directory of Open Access Journals (Sweden)

    Takayuki Iwaki

    2016-01-01

    Full Text Available Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses in discrete stages and involves a number of cell types and effector molecules. Recently, [18F]fluoro-2-deoxy-D-glucose- ([18F]FDG- positron emission tomography (PET has been suggested as a tool to evaluate atherosclerotic plaques by detecting accumulated macrophages associated with inflammation progress. However, at the cellular level, it remains unknown whether only macrophages exhibit high uptake of [18F]FDG. To identify the cellular origin of [18F]FDG uptake in atherosclerotic plaques, we developed a simian atherosclerosis model and performed PET and ex vivo macro- and micro-autoradiography (ARG. Increased [18F]FDG uptake in the aortic wall was observed in high-cholesterol diet-treated monkeys and WHHL rabbits. Macro-ARG of [18F]FDG in aortic sections showed that [18F]FDG was accumulated in the media and intima in the simian model as similar to that in WHHL rabbits. Combined analysis of micro-ARG with immunohistochemistry in the simian atherosclerosis model revealed that most cellular [18F]FDG uptake observed in the media was derived not only from the infiltrated macrophages in atherosclerotic plaques but also from the smooth muscle cells (SMCs of the aortic wall in atherosclerotic lesions.

  4. Treatment Strategy Based on Plaque Vulnerability and the Treatment Risk Evaluation for Internal Carotid Artery Stenosis.

    Science.gov (United States)

    Ito, Yoshiro; Tsuruta, Wataro; Nakai, Yasunobu; Takigawa, Tomoji; Marushima, Aiki; Masumoto, Tomohiko; Matsumaru, Yuji; Ishikawa, Eiichi; Matsumura, Akira

    2018-03-03

    Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are not appropriate treatment procedure for internal carotid artery stenosis (ICAS) in some patients. The importance of plaque vulnerability and the treatment risk evaluation has been reported. We analyzed whether treatment selection contributes to the outcome. We retrospectively examined 121 patients who underwent CEA or CAS. Treatment was selected based on plaque vulnerability and the treatment risk evaluation. We selected CAS for patients with stable plaques and CEA for patients with unstable plaques, and considered the other treatment for high-risk patients. The patients were classified as the stable plaque (Stable: n = 42), the unstable plaque and CEA low risk (Unstable/Low: n = 30), and the CEA high-risk (Unstable/High: n = 49). Frequency of perioperative stroke, myocardial infarction, death, and systemic complications was examined. CEA and CAS were performed in 35 and 86 patients, respectively. One patient (2.9%) had a stroke in CEA and five patients (5.8%) in CAS (P = 0.50). Systemic complications were observed in two patients (5.7%) in CEA and six (7.1%) in CAS (P = 0.80). There were no differences in stroke (Stable; 2.4%, Unstable/Low; 3.2%, and Unstable/High; 8.2%) and systemic complications (Stable; 9.5%, Unstable/Low; 3.3%, and Unstable/High; 6.1%) among three groups (P = 0.44 and P = 0.59, respectively). The treatment selection based on plaque vulnerability and the treatment risk evaluation could provide good treatment outcome for high-risk patients. It is ideal to select an appropriate treatment for ICAS by one neurovascular team.

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

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    Shaoqun Zhang

    2017-01-01

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

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

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    Đurić Tamara

    2013-01-01

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

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

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    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.

  8. The role of contrast-enhanced ultrasound in risk assessment of carotid atheroma

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    Silviu Stanciu

    2016-07-01

    Full Text Available Background and objective: Contrast-enhanced ultrasound, used to assess atherosclerotic carotid plaques, improves visualization of vessel wall irregularities and depicts intraplaque neovascularization. This article illustrates the use of contrast-enhanced ultrasound in the risk assessment of carotid atherosclerotic lesions, especially in challenging plaques evaluation. Materials and methods: For 23 patients with difficult duplex ultrasound examination due to carotid tortuosity or calcifications we assessed plaque morphology (contour, echogenicity and stenosis degree using contrast substance (Sonovue, Braco with dedicated vascular low mechanical index CPC software. Conclusion: Contrast-enhanced ultrasound is a new, noninvasive, and safe procedure for imaging carotid atherosclerotic lesions. It is a valuable tool for evaluating the vulnerable plaque at risk for rupture and for the diagnostic of the development and severity of systemic atherosclerotic disease

  9. Relationship between dyslipidemia and carotid plaques in a high-stroke-risk population in Shandong Province, China.

    Science.gov (United States)

    Mi, Te; Sun, Shangwen; Zhang, Guoqing; Carora, Yaser; Du, Yifeng; Guo, Shougang; Cao, Mingfeng; Zhu, Qiang; Wang, Yongxiang; Sun, Qinjian; Wang, Xiang; Qu, Chuanqiang

    2016-06-01

    The precise associations between stroke and carotid plaques and dyslipidemia are unclear. This population-based study aimed to examine the relationship between carotid plaques and dyslipidemia in a high-stroke-risk population. Ultrasonography of left and right carotid arteries was conducted in 22,222 participants in a second screening survey of individuals with high stroke risk. Subjects were divided into two groups according to the presence or absence of carotid plaques. Blood TC (total cholesterol), TG (total triglycerides), and LDL-C (low-density lipoprotein cholesterol) levels were recorded. Multivariate logistic regression analysis, controlled for gender, age, education, geographic region, smoking, exercise, and overweight (Model 2), identified TG as a predictor of carotid-plaque risk (odds ratio [OR] = 1.109, 95% confidence interval [CI]: 1.038-1.185, P = 0.002), and the association between carotid plaques and LDL-C (OR = 0.967, 95%CI: 0.949-0.994, P = 0.019) was less significant, whereas there was no association between carotid plaques and TC (OR = 1.002, 95%CI: 0.932-1.007, P = 0.958). After additional adjustment for hypertension, diabetes, and atrial fibrillation (Model 3), TG remained a risk factor for carotid plaques (OR = 1.086, 95%CI: 1.016-1.161, P = 0.015), but no associations were observed between carotid plaques and LDL-C (OR = 0.972, 95%CI: 0.910-1.038, P = 0.394) or TC (OR = 1.003, 95%CI: 0.933-1.079, P = 0.928). Only the association between TG and carotid plaques (OR = 1.084, 95%CI: 1.014-1.159, P = 0.017) was independent of all covariates (covariates in Model 3 plus history of stroke or transient ischemic attack, and stroke family history) in Model 4. These findings indicate that TG was an independent risk factor for carotid plaques in high-risk population for stroke, whereas LDL-C and TC were not associated with the appearance of carotid plaques independently.

  10. Computational and experimental assessment of influences of hemodynamic shear stress on carotid plaque.

    Science.gov (United States)

    Zhou, Hui; Meng, Long; Zhou, Wei; Xin, Lin; Xia, Xiangxiang; Li, Shuai; Zheng, Hairong; Niu, Lili

    2017-07-29

    Studies have identified hemodynamic shear stress as an important determinant of endothelial function and atherosclerosis. In this study, we assess the influences of hemodynamic shear stress on carotid plaques. Carotid stenosis phantoms with three severity (30, 50, 70%) were made from 10% polyvinyl alcohol (PVA) cryogel. The phantoms were placed in a pulsatile flow loop with the same systolic/diastolic phase (35/65) and inlet flow rate (16 L/h). Ultrasonic particle imaging velocimetry (Echo PIV) and computational fluid dynamics (CFD) were used to calculate the velocity profile and shear stress distribution in the carotid stenosis phantoms. Inlet/outlet boundary conditions used in CFD were extracted from Echo PIV experiments to make sure that the results were comparable. Echo PIV and CFD results showed that velocity was largest in 70% than those in 30 and 50% at peak systole. Echo PIV results indicated that shear stress was larger in the upper wall and the surface of plaque than in the center of vessel. CFD results demonstrated that wall shear stress in the upstream was larger than in downstream of plaque. There was no significant difference in average velocity obtained by CFD and Echo PIV in 30% (p = 0.25). Velocities measured by CFD in 50% (93.01 cm/s) and in 70% (115.07 cm/s) were larger than those by Echo PIV in 50% (60.26 ± 5.36 cm/s) and in 70% (89.11 ± 7.21 cm/s). The results suggested that Echo PIV and CFD could obtain hemodynamic shear stress on carotid plaques. Higher WSS occurred in narrower arteries, and the shoulder of plaque bore higher WSS than in bottom part.

  11. 3D MRI-based anisotropic FSI models with cyclic bending for human coronary atherosclerotic plaque mechanical analysis.

    Science.gov (United States)

    Tang, Dalin; Yang, Chun; Kobayashi, Shunichi; Zheng, Jie; Woodard, Pamela K; Teng, Zhongzhao; Billiar, Kristen; Bach, Richard; Ku, David N

    2009-06-01

    Heart attack and stroke are often caused by atherosclerotic plaque rupture, which happens without warning most of the time. Magnetic resonance imaging (MRI)-based atherosclerotic plaque models with fluid-structure interactions (FSIs) have been introduced to perform flow and stress/strain analysis and identify possible mechanical and morphological indices for accurate plaque vulnerability assessment. For coronary arteries, cyclic bending associated with heart motion and anisotropy of the vessel walls may have significant influence on flow and stress/strain distributions in the plaque. FSI models with cyclic bending and anisotropic vessel properties for coronary plaques are lacking in the current literature. In this paper, cyclic bending and anisotropic vessel properties were added to 3D FSI coronary plaque models so that the models would be more realistic for more accurate computational flow and stress/strain predictions. Six computational models using one ex vivo MRI human coronary plaque specimen data were constructed to assess the effects of cyclic bending, anisotropic vessel properties, pulsating pressure, plaque structure, and axial stretch on plaque stress/strain distributions. Our results indicate that cyclic bending and anisotropic properties may cause 50-800% increase in maximum principal stress (Stress-P1) values at selected locations. The stress increase varies with location and is higher when bending is coupled with axial stretch, nonsmooth plaque structure, and resonant pressure conditions (zero phase angle shift). Effects of cyclic bending on flow behaviors are more modest (9.8% decrease in maximum velocity, 2.5% decrease in flow rate, 15% increase in maximum flow shear stress). Inclusion of cyclic bending, anisotropic vessel material properties, accurate plaque structure, and axial stretch in computational FSI models should lead to a considerable improvement of accuracy of computational stress/strain predictions for coronary plaque vulnerability

  12. Effect of butylphthalide soft capsule on the anti-inflammatory effect and plaque stability in patients with ischemic cerebrovascular disease and carotid atherosclerosis

    Directory of Open Access Journals (Sweden)

    Kun Wang

    2017-06-01

    significantly reduced when compared with before treatment. The unstable plaque number after treatment in the intervention 1 group was significantly lower than that in the intervention 2 group. Conclusions: Butylphthalide soft capsule can resist the inflammation, reverse the prolieration of carotid intima, stabilize the vulnerable plaque, and remove the non-atherosclerotic plaque.

  13. Osteoprotegerin, pericytes and bone-like vascular calcification are associated with carotid plaque stability.

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    Jean-Michel Davaine

    Full Text Available BACKGROUND AND PURPOSE: Vascular calcification, recapitulating bone formation, has a profound impact on plaque stability. The aim of the present study was to determine the influence of bone-like vascular calcification (named osteoid metaplasia = OM and of osteoprotegerin on plaque stability. METHODS: Tissue from carotid endarterectomies were analysed for the presence of calcification and signs of vulnerability according to AHA grading system. Osteoprotegerin (OPG, pericytes and endothelial cells were sought using immuno-histochemistry. Symptoms and preoperative imaging findings (CT-scan, MRI and Doppler-scan were analyzed. Human pericytes were cultured to evaluate their ability to secrete OPG and to influence mineralization in the plaque. RESULTS: Seventy-three carotid plaques (49 asymptomatic and 24 symptomatic were harvested. A significantly higher presence of OM (18.4% vs 0%, p<0.01, OPG (10.2% of ROI vs 3.4% of ROI, p<0.05 and pericytes (19% of ROI vs 3.8% of ROI, p<0.05 were noted in asymptomatic compared to symptomatic plaques. Consistently, circulating OPG levels were higher in the plasma of asymptomatic patients (3.2 ng/mL vs 2.5 ng/mL, p = 0.05. In vitro, human vascular pericytes secreted considerable amounts of OPG and underwent osteoblastic differentiation. Pericytes also inhibited the osteoclastic differentiation of CD14+ cells through their secretion of OPG. CONCLUSIONS: OPG (intraplaque an plasmatic and OM are associated with carotid plaque stability. Pericytes may be involved in the secretion of intraplaque OPG and in the formation of OM.

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

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    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.

  15. Characterisation of carotid plaques with ultrasound elastography: feasibility and correlation with high-resolution magnetic resonance imaging

    International Nuclear Information System (INIS)

    Naim, Cyrille; Cloutier, Guy; Mercure, Elizabeth; Destrempes, Francois; Qin, Zhao; El-Abyad, Walid; Lanthier, Sylvain; Giroux, Marie-France; Soulez, Gilles

    2013-01-01

    To evaluate the ability of ultrasound non-invasive vascular elastography (NIVE) strain analysis to characterise carotid plaque composition and vulnerability as determined by high-resolution magnetic resonance imaging (MRI). Thirty-one subjects with 50 % or greater carotid stenosis underwent NIVE and high-resolution MRI of internal carotid arteries. Time-varying strain images (elastograms) of segmented plaques were generated from ultrasonic raw radiofrequency sequences. On MRI, corresponding plaques and components were segmented and quantified. Associations between strain parameters, plaque composition and symptomatology were estimated with curve-fitting regressions and Mann-Whitney tests. Mean stenosis and age were 72.7 % and 69.3 years, respectively. Of 31 plaques, 9 were symptomatic, 17 contained lipid and 7 were vulnerable on MRI. Strains were significantly lower in plaques containing a lipid core compared with those without lipid, with 77-100 % sensitivity and 57-79 % specificity (P < 0.032). A statistically significant quadratic fit was found between strain and lipid content (P < 0.03). Strains did not discriminate symptomatic patients or vulnerable plaques. Ultrasound NIVE is feasible in patients with significant carotid stenosis and can detect the presence of a lipid core with high sensitivity and moderate specificity. Studies of plaque progression with NIVE are required to identify vulnerable plaques. (orig.)

  16. The correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease

    Directory of Open Access Journals (Sweden)

    Yan-Bing Xi

    2017-04-01

    Full Text Available Objective: To study the correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease. Methods: A total of 80 patients with coronary heart disease who were treated in our hospital between January 2013 and April 2016 were collected as the observation group, and 50 healthy subjects who received medical examination in our hospital during the same period were selected as the normal control group. Serum PDGF and Ang-2 contents of two groups of patients were detected, and the observation group were further divided into the high PDGF group and low PDGF group (n = 40 as well as the high Ang-2 group and low Ang-2 group (n = 40 according to the median of PDGF and Ang-2 contents. Ultrasonic contrast technology was used to assess the atherosclerotic plaque characteristics in patients with coronary heart disease. Results: Serum PDGF and Ang-2 contents of observation group were significantly higher than those of control group; ultrasound parameters P and AUC levels of high PDGF group were higher than those of low PDGF group while Tp and MTT levels were lower than those of low PDGF group; ultrasound parameters P and AUC levels of high Ang-2 group were higher than those of low Ang-2 group while Tp and MTT levels were lower than those of low Ang-2 group. Conclusion: Serum PDGF and Ang-2 contents increase in patients with coronary heart disease and are negatively correlated with the atherosclerotic plaque stability.

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

    International Nuclear Information System (INIS)

    Jang, Moon Kyoo; Kim, Ji Young; Jeoung, Nam Ho; Kang, Mi Ae; Choi, Myung-Sook; Oh, Goo Taeg; Nam, Kyung Tak; Lee, Won-Ha; Park, Yong Bok

    2004-01-01

    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

  18. Serum Osteoprotegerin Is Associated With Calcified Carotid Plaque: A Strobe-Compliant Observational Study.

    Science.gov (United States)

    Kwon, Ami; Choi, Yun-Seok; Choi, Yong-Won; Chung, Woo-Baek; Park, Chul-Soo; Chung, Wook-Sung; Lee, Man-Young; Youn, Ho-Joong

    2016-04-01

    Osteoprotegerin (OPG) is a kind of tumor necrosis factor, which is related to bone metabolism and vascular calcification. The increase of Osteoprotegerin concentration in serum is related to cardiovascular diseases in humans. The purpose of this study was to figure out the relevance between osteoprotegerin in serum and carotid calcification. Serum OPG concentrations were compared in 145 patients who underwent carotid sonography (average age: 68 ± 9 years old, male: female = 81:64). A calcified plaque (CP) (37 people [27%]), a noncalcified plaque (NCP) (54 people [37%]), and a nonplaque (NP) (54 people [37%]) were classified for this study. No significant differences among 3 groups were demonstrated in the distribution of age, diabetes, high blood pressure, and hyperlipidemia. Serum osteoprotegerin concentrations were significantly increased in CP group rather than NCP group or NP group; (median [interquartile range], 4016 [1410] vs 3210 [1802] pg/mL, P osteoprotegerin concentrations did not indicate a significant difference between NCP Group or NP Group. This study had proved that patient group accompanied with carotid calcification in carotid artery disease had an increased serum OPG concentration, so it could consider that OPG plays an important function on calcification related to arteriosclerosis.

  19. The role of damage- and pathogen-associated molecular patterns in inflammation-mediated vulnerability of atherosclerotic plaques.

    Science.gov (United States)

    Rai, Vikrant; Agrawal, Devendra K

    2017-10-01

    Atherosclerosis is a chronic inflammatory disease resulting in the formation of the atherosclerotic plaque. Plaque formation starts with the inflammation in fatty streaks and progresses through atheroma, atheromatous plaque, and fibroatheroma leading to development of stable plaque. Hypercholesterolemia, dyslipidemia, and hyperglycemia are the risk factors for atherosclerosis. Inflammation, infection with viruses and bacteria, and dysregulation in the endothelial and vascular smooth muscle cells leads to advanced plaque formation. Death of the cells in the intima due to inflammation results in secretion of damage-associated molecular patterns (DAMPs) such as high mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), alarmins (S100A8, S100A9, S100A12, and oxidized low-density lipoproteins), and infection with pathogens leads to secretion of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides, lipoteichoic acids, and peptidoglycans. DAMPs and PAMPs further activate the inflammatory surface receptors such as TREM-1 and toll-like receptors and downstream signaling kinases and transcription factors leading to increased secretion of pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-1β, IL-6, and interferon-γ and matrix metalloproteinases (MMPs). These mediators and cytokines along with MMPs render the plaque vulnerable for rupture leading to ischemic events. In this review, we have discussed the role of DAMPs and PAMPs in association with inflammation-mediated plaque vulnerability.

  20. 2D versus 3D cross-correlation-based radial and circumferential strain estimation using multiplane 2D ultrafast ultrasound in a 3D atherosclerotic carotid artery model.

    Science.gov (United States)

    Fekkes, Stein; Swillens, Abigail E S; Hansen, Hendrik H G; Saris, Anne E C M; Nillesen, Maartje M; Iannaccone, Francesco; Segers, Patrick; de Korte, Chris L

    2016-08-25

    Three-dimensional strain estimation might improve the detection and localization of high strain regions in the carotid artery for identification of vulnerable plaques. This study compares 2D vs. 3D displacement estimation in terms of radial and circumferential strain using simulated ultrasound images of a patient specific 3D atherosclerotic carotid artery model at the bifurcation embedded in surrounding tissue generated with ABAQUS software. Global longitudinal motion was superimposed to the model based on literature data. A Philips L11-3 linear array transducer was simulated which transmitted plane waves at 3 alternating angles at a pulse repetition rate of 10 kHz. Inter-frame radiofrequency ultrasound data were simulated in Field II for 191 equally spaced longitudinal positions of the internal carotid artery. Accumulated radial and circumferential displacements were estimated using tracking of the inter-frame displacements estimated by a two-step normalized cross-correlation method and displacement compounding. Least squares strain estimation was performed to determine accumulated radial and circumferential strain. The performance of the 2D and 3D method was compared by calculating the root-mean-squared error of the estimated strains with respect to the reference strains obtained from the model. More accurate strain images were obtained using the 3D displacement estimation for the entire cardiac cycle. The 3D technique clearly outperformed the 2D technique in phases with high inter-frame longitudinal motion. In fact the large inter-frame longitudinal motion rendered it impossible to accurately track the tissue and cumulate strains over the entire cardiac cycle with the 2D technique.

  1. Prediction of carotid plaque characteristics using non-gated MR imaging: correlation with endarterectomy specimens.

    Science.gov (United States)

    Narumi, S; Sasaki, M; Ohba, H; Ogasawara, K; Kobayashi, M; Hitomi, J; Mori, K; Ohura, K; Yamaguchi, M; Kudo, K; Terayama, Y

    2013-01-01

    Electrocardiographic gating, commonly used in MR carotid plaque imaging, can negatively affect intraplaque contrast if the TR is inappropriate. The present study aimed to determine whether a non-gated technique with appropriate TRs can accurately evaluate intraplaque characteristics in specimens excised by CEA. We prospectively examined 40 consecutive patients who underwent CEA (59-82 years of age) by using a 1.5T scanner. Axial T1WI with a TR of 500 ms and PDWI and T2WI with a TR of 3000 ms with a self-navigated rotating-blade scan instead of cardiac gating were obtained. Signal intensities of the plaque and adjacent muscle were measured, and the CR on T1WI, PDWI, and T2WI as well as the gray-scale median on US were correlated with the pathologic findings of the CEA specimens. On T1WI, the CRs of the carotid plaques differed significantly among groups in which the main components were histologically confirmed as fibrous tissue, lipid/necrosis, and hemorrhage (0.54-1.17, 1.16-1.53, and 1.40-2.29, respectively). The sensitivity and specificity for discriminating lipid/necrosis/hemorrhage from fibrous tissue were 96% and 100%, respectively. On T2WI, the CRs of plaques with lipid/necrosis were significantly higher than those of other groups, but the CRs on PDWI and the gray-scale median on US were not significantly different among the groups. Non-gated MR plaque imaging, particularly T1WI, can readily predict the intraplaque main components of the carotid artery with high sensitivity and specificity.

  2. 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

  3. Multi-center MRI carotid plaque component segmentation using feature normalization and transfer learning

    DEFF Research Database (Denmark)

    van Engelen, Arna; van Dijk, Anouk C; Truijman, Martine T.B.

    2015-01-01

    weights. Results showed that the best results were obtained for a combination of feature normalization and transfer learning. While for the other approaches significant differences in voxelwise or mean volume errors were found compared with the reference samecenter training, the proposed approach did......Automated segmentation of plaque components in carotid artery MRI is important to enable large studies on plaque vulnerability, and for incorporating plaque composition as an imaging biomarker in clinical practice. Especially supervised classification techniques, which learn from labeled examples...... with two approaches that use little or no annotated same-center data. These approaches additionally use an annotated set of differentcenter data. We evaluate 1) a non-linear feature normalization approach, and 2) two transfer-learning algorithms that use same and different-center data with different...

  4. Effects of carotid endarterectomy on cognitive functioning and perceived health

    NARCIS (Netherlands)

    Bossema, E.R.

    2005-01-01

    Carotid endarterectomy (CEA) is a surgical procedure to remove atherosclerotic plaque from the carotid arteries. It has become a routine surgical procedure for the prevention of stroke in patients with severe occlusive disease. The main aim of this thesis was to investigate the possible beneficial

  5. Circulating CD45+/CD3+ lymphocyte-derived microparticles map lipid-rich atherosclerotic plaques in familial hypercholesterolaemia patients.

    Science.gov (United States)

    Suades, Rosa; Padró, Teresa; Alonso, Rodrigo; López-Miranda, José; Mata, Pedro; Badimon, Lina

    2014-01-01

    Circulating microparticles (cMPs) seem to play important roles in vascular function. Beyond markers of activated cells, cMPs may have potential paracrine functions and influence atherosclerosis. Here, our objective was to characterise a) the abundance and phenotype of cMPs in stable statin-treated heterozygous familial hypercholesterolaemia (FH) patients exposed to life-long hypercholesterolaemia and b) the principal phenotype associated to lipid-rich atherosclerotic plaques in hFH-patients with significant atherosclerotic plaque burden. An age/gender/treatment-matched group of adult-onset non-FH hypercholesterolaemic patients (n=37/group) was comparatively analysed. cMPs were characterised by flow cytometry using annexin-V and cell surface-specific antibodies. Our study shows that LLT-FH patients had higher overall cMP-numbers (pderived cMP-subpopulations, FH-patients had significantly higher lymphocyte- and monocyte-derived cMP-numbers as well as cMPs carrying leukocyte-activation markers. Normalisation of cMPs by LDL levels did not affect cMP number or phenotype, indicating that the proinflammatory effect was derived from chronic vascular damage. Levels of AV+-total, CD45+-pan-leukocyte and CD45+/CD3+-lymphocyte-derived cMPs were significantly higher in FH-patients with subclinical lipid-rich atherosclerotic plaques than fibrous plaques. Levels of CD45+/CD3+-lymphocyte-MPs above 20,000/ml could differentiate between FH-patients with lipidic or non-lipidic plaques (area under the ROC curve of 0.803, 95%CI: 0.641-0.965, p=0.008). In summary, in this snapshot cross-sectional study cMP concentration and phenotype in FH differed markedly from non-FH hypercholesterolaemia. Patients with life-long high LDL exposure have higher endothelial activation and higher proinflammatory profile, even under current state-of-the-art LLT. cMPs carrying lymphocyte-epitopes appear as markers of lipid-rich atherosclerotic plaques in FH.

  6. Atherosclerotic Plaque Characteristics by CT Angiography Identify Coronary Lesions That Cause Ischemia: a Direct Comparison to Fractional Flow Reserve

    Science.gov (United States)

    Park, Hyung-Bok; Heo, Ran; Hartaigh, Bríain ó; Cho, Iksung; Gransar, Heidi; Nakazato, Ryo; Leipsic, Jonathon; Mancini, G.B. John; Koo, Bon-Kwon; Otake, Hiromasa; Budoff, Matthew J.; Berman, Daniel S.; Erglis, Andrejs; Chang, Hyuk-Jae; Min, James K.

    2014-01-01

    Objective We evaluated the association between atherosclerotic plaque characteristics (APCs) by coronary CT angiography (CT) and lesion ischemia by fractional flow reserve (FFR). Background FFR is the gold standard for determining lesion ischemia. While APCs by CT—including aggregate plaque volume % (%APV), positive remodeling (PR), low attenuation plaque (LAP) and spotty calcification (SC)—are associated with future coronary syndromes, their relationship to lesion ischemia is unclear. Methods 252 patients (17 centers, 5 countries) [mean age 63 years, 71% males] underwent CT, with FFR performed for 407 coronary lesions. CT was interpreted for 50% stenosis, with the latter considered obstructive. APCs by CT were defined as: (1) PR, lesion diameter/reference diameter >1.10; (2) LAP, any voxel 50% but not for 50%. PMID:25592691

  7. Joint learning of ultrasonic backscattering statistical physics and signal confidence primal for characterizing atherosclerotic plaques using intravascular ultrasound.

    Science.gov (United States)

    Sheet, Debdoot; Karamalis, Athanasios; Eslami, Abouzar; Noël, Peter; Chatterjee, Jyotirmoy; Ray, Ajoy K; Laine, Andrew F; Carlier, Stephane G; Navab, Nassir; Katouzian, Amin

    2014-01-01

    Intravascular Ultrasound (IVUS) is a predominant imaging modality in interventional cardiology. It provides real-time cross-sectional images of arteries and assists clinicians to infer about atherosclerotic plaques composition. These plaques are heterogeneous in nature and constitute fibrous tissue, lipid deposits and calcifications. Each of these tissues backscatter ultrasonic pulses and are associated with a characteristic intensity in B-mode IVUS image. However, clinicians are challenged when colocated heterogeneous tissue backscatter mixed signals appearing as non-unique intensity patterns in B-mode IVUS image. Tissue characterization algorithms have been developed to assist clinicians to identify such heterogeneous tissues and assess plaque vulnerability. In this paper, we propose a novel technique coined as Stochastic Driven Histology (SDH) that is able to provide information about co-located heterogeneous tissues. It employs learning of tissue specific ultrasonic backscattering statistical physics and signal confidence primal from labeled data for predicting heterogeneous tissue composition in plaques. We employ a random forest for the purpose of learning such a primal using sparsely labeled and noisy samples. In clinical deployment, the posterior prediction of different lesions constituting the plaque is estimated. Folded cross-validation experiments have been performed with 53 plaques indicating high concurrence with traditional tissue histology. On the wider horizon, this framework enables learning of tissue-energy interaction statistical physics and can be leveraged for promising clinical applications requiring tissue characterization beyond the application demonstrated in this paper. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Rosuvastatin reduces intima-media thickness in hypercholesterolemic subjects with asymptomatic carotid artery disease: the Asymptomatic Carotid Atherosclerotic Disease in Manfredonia (ACADIM) Study.

    Science.gov (United States)

    Riccioni, Graziano; Bazzano, Lydia A; Bucciarelli, Tonino; Mancini, Barbara; di Ilio, Emanuela; D'Orazio, Nicolantonio

    2008-10-01

    An increase in carotid intima-media thickness (CIMT) represents an early phase of the atherosclerotic process. The aim of this study was to evaluate whether a reduction in CIMT could be seen with only 16 weeks of treatment with rosuvastatin (10 mg/day). Sixty-six participants of the ACADIM Study with hypercholesterolemia and carotid atherosclerosis at baseline carotid ultrasound investigation (CUI) were examined, with repeat CUI after 16 weeks of treatment. Demographic and lifestyle data were collected, as well as physical examination and fasting venous blood samples. Total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides decreased significantly (p < 0.0001), while high density lipoprotein cholesterol (HDL-C) increased significantly (p < 0.0001) during the intervention. The mean decrease in IMT of the right and left common carotid arteries (CCAs) was 0.35 and 0.38 mm, respectively (p < 0.05 for each). Age and lipid profile parameters were significant predictors of change in CIMT in linear regression analyses after adjustment for established atherosclerosis risk factors. Treatment with rosuvastatin in adults with evidence of subclinical atherosclerosis significantly reduced the CIMT of both CCAs, as well as improving lipid and lipoprotein levels.

  9. [Carotid artery wall perfusion of the plaque: three dimensional contrast sonographic imaging].

    Science.gov (United States)

    Nakaoka, Tsutomu; Shoji, Hidehiko; Tabeta, Hideyuki; Ikeshima, Hiroaki; Uchida, Tamao; Itou, Kenjirou

    2008-11-01

    We usually check stenosis rate in patients through the limited directions of angiography. This can result in insufficient evaluation. The importance of the condition of the carotid artery wall in fully accpted nowadays, and ultrasound sonography is being used as a means to study it. Neovascularization in the plaque is one of the pathological factors inducing plaque hemorrhage and rupture, and this is suspected of causing carotid artery stenosis, occlusion and artery-to-artery embolism. Harmonic image is a contrast specific imaging modality, which uses the nonlinear properties of ultrasound contrast agents by transmitting at the fundamental frequency and receiving at multiples of these frequencies. Pulse inversion harmonic image (PIHI), using pulse inversion to eliminate and strengthen the harmonic frequency, is more effective than conventional harmonic imaging. We can detect tissue perfusion by contrast sonographic imaging with PIHI. The routes of vascular wall feeding are as follows: One is diffusion through the endothelium and the other is through the vasa vasorum to the outer part of the medium. So there is no neovascularization at the inner side of the carotid artery. But some plaques have neovascularization in themselves, so we have tried to detect them by the intermittent and real time contrast sonographic imaging method with PIHI. We have already reported the evaluation of neovascularization by the intermittent method and classified from type I to type IV according to the distribution of neovascular vessels in the plaque. The real time contrast sonographic imaging method with PIHI has revealed some characters of neovascularization. Furthermore NV was observed through the real time 3D CAWP by matrix array, though there are some problem for the clinical application.

  10. Nonlinear registration of serial coronary CT angiography (CCTA) for assessment of changes in atherosclerotic plaque

    International Nuclear Information System (INIS)

    Woo, Jonghye; Dey, Damini; Cheng, Victor Y.; Hong, Byung-Woo; Ramesh, Amit; Sundaramoorthi, Ganesh; Nakazato, Ryo; Berman, Daniel S.; Germano, Guido; Kuo, C.-C. Jay; Slomka, Piotr J.

    2010-01-01

    deformation was 0.14±0.06 mm. The observer variability between two expert observers was 1.31±0.91 mm. Conclusions: The proposed coregistration algorithm demonstrates potential to accurately register serial CCTA scans, which may allow direct comparison of calcified and noncalcified atherosclerotic plaque changes between the two scans.

  11. The effect of aging on aortic atherosclerotic plaque inflammation and molecular calcification: A FDG and NaF PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

    2013-01-01

    Objectives: Aging is an important independent determinant of plaque biology. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and calcification metabolism. Methods: Thirteen healthy volunteers without traditional cardiovascular risk factors were...... and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18-FDG and aortic Na-18F avidity. A second order polynomial regression established that aging is a predictor of the degree of aortic plaque inflammation (R = 0.524; F statistic = 4.93; P = 0...... data, a quadratic relationship appears to exist between aging and plaque inflammation. Furthermore, a quadratic relationship was observed between aging and plaque calcification metabolism. In line with these observations, a linear relationship was observed between atherosclerotic plaque inflammation...

  12. {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.)

  13. 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.

  14. 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.)

  15. Risk factors of carotid plaque and carotid common artery intima-media thickening in a high-stroke-risk population.

    Science.gov (United States)

    Wang, ChunFang; Lv, GaoPeng; Zang, DaWei

    2017-11-01

    To analyze the risk factors of carotid plaque (CP) and carotid common artery intima-media thickening (CCAIMT) and the association between the risk factors and CP numbers and the side of the CCAIMT in a high-stroke-risk population. Carotid ultrasonography was conducted in 2025 participants with high stroke risk. Participants were divided into different groups according to the results of the ultrasound. The risk factors and blood biochemical indices were recorded. The presence of CP and CCAIMT were 38.9% and 24.8% respectively. Multivariate logistic regression indicated that the risk factors of CP were age, high LDL-C and FBG levels, male gender, stroke, diabetes, hypertension, and tobacco use. Compared with participants without CPs, the participants who were male, and older in age, with risk factors of tobacco use, diabetes, high LDL-C levels, and a family history of hypertension were likely to have a single CP, whereas the participants with risk factors of tobacco use, diabetes, hypertension, male gender, older age, high LDL-C levels, stroke and AF or valvulopathy were prone to have multiple CPs. The risk factors of CCAIMT were male gender, stroke, hypertension, diabetes, AF or valvulopathy, tobacco use and age. Compared with the N-CCAIMT subgroup, the risk factors of left CCAIMT were tobacco use, diabetes, male gender, and age. The risk factors of right CCAIMT were male gender, high FBG levels, age, AF or valvulopathy. The risk factors of dual CCAIMT were high frequency of drinking milk, tobacco use, male gender, age, stroke, and hypertension. These findings revealed the risk factors of CP and CCAIMT, and an association between the risk factors and the CP numbers and the side of the CCAIMT.

  16. Pre-operative Carotid Plaque Echolucency Assessment has no Predictive Value for Long-Term Risk of Stroke or Cardiovascular Death in Patients Undergoing Carotid Endarterectomy.

    Science.gov (United States)

    de Waard, D; de Borst, G J; Bulbulia, R; Pan, H; Halliday, A

    2017-08-01

    In patients with carotid stenosis receiving medical treatment, carotid plaque echolucency has been thought to predict risk of future stroke and of other cardiovascular events. This study evaluated the prognostic value of pre-operative plaque echolucency for future stroke and cardiovascular death in patients undergoing carotid endarterectomy in the first Asymptomatic Carotid Surgery Trial (ACST-1). In ACST-1, 1832/3120 patients underwent carotid endarterectomy (CEA), of whom 894 had visual echolucency assessment according to the Gray-Weale classification. During follow-up patients were monitored both for peri-procedural (i.e. within 30 days) death, stroke, or MI, and for long-term risk of stroke or cardiovascular death. Unconditional maximum likelihood estimation was used to calculate odds ratios of peri-procedural risk and Kaplan-Meier statistics with log-rank test were used to compare cumulative long-term risks. Of 894 operated patients in whom echolucency was assessed, 458 plaques (51%) were rated as echolucent and peri-procedural risk of death/stroke/MI in these patients was non-significantly higher when compared with patients with non-echolucent plaques (OR 1.48 [95% CI 0.76-2.88], p = .241). No differences were found in the 10 year risk of any stroke (30/447 [11.6%] vs. 29/433 [11.0%], p = .900) or cardiovascular (non-stroke) death (85/447 [27.9%] vs. 93/433 [32.1%], p = .301). In ACST-1, carotid plaque echolucency assessment in patients undergoing CEA offered no predictive value with regard to peri-operative or long-term stroke risk or of cardiovascular (non-stroke) death. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Fabrizio Montecucco

    2007-01-01

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

  18. Genetic variation within the Y chromosome is not associated with histological characteristics of the atherosclerotic carotid artery or aneurysmal wall.

    Science.gov (United States)

    Haitjema, Saskia; van Setten, Jessica; Eales, James; van der Laan, Sander W; Gandin, Ilaria; de Vries, Jean-Paul P M; de Borst, Gert J; Pasterkamp, Gerard; Asselbergs, Folkert W; Charchar, Fadi J; Wilson, James F; de Jager, Saskia C A; Tomaszewski, Maciej; den Ruijter, Hester M

    2017-04-01

    Haplogroup I, a common European paternal lineage of the Y chromosome, is associated with increased risk of coronary artery disease in British men. It is unclear whether this haplogroup or any other haplogroup on the Y chromosome is associated with histological characteristics of the diseased vessel wall in other vascular manifestations of cardiovascular diseases showing a male preponderance. We examined Dutch men undergoing either carotid endarterectomy from the Athero-Express biobank (AE, n = 1217) or open aneurysm repair from the Aneurysm-Express biobank (AAA, n = 393). Upon resolving the Y chromosome phylogeny, each man was assigned to one of the paternal lineages based on combinations of single nucleotide polymorphisms of the male-specific region of the Y chromosome. We examined the associations between the Y chromosome and the histological characteristics of the carotid plaque and aneurysm wall, including lipid content, leukocyte infiltration and intraplaque haemorrhage, in all men. A majority of men were carriers of either haplogroup I (AE: 28% AAA: 24%) or haplogroup R (AE: 59% AAA: 61%). We found no association between Y chromosomal haplogroups and histological characteristics of plaque collected from carotid arteries or tissue specimens of aneurysms. Moreover, the distribution of frequency for all Y chromosomal haplogroups in both cohorts was similar to that of a general population of Dutch men. Our data show that genetic variation on the Y chromosome is not associated with histological characteristics of the plaques from carotid arteries or specimens of aneurysms in men of Dutch origin. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Proteomic Analysis of Plasma-Purified VLDL, LDL, and HDL Fractions from Atherosclerotic Patients Undergoing Carotid Endarterectomy: Identification of Serum Amyloid A as a Potential Marker

    Directory of Open Access Journals (Sweden)

    Antonio J. Lepedda

    2013-01-01

    Full Text Available Apolipoproteins are very heterogeneous protein family, implicated in plasma lipoprotein structural stabilization, lipid metabolism, inflammation, or immunity. Obtaining detailed information on apolipoprotein composition and structure may contribute to elucidating lipoprotein roles in atherogenesis and to developing new therapeutic strategies for the treatment of lipoprotein-associated disorders. This study aimed at developing a comprehensive method for characterizing the apolipoprotein component of plasma VLDL, LDL, and HDL fractions from patients undergoing carotid endarterectomy, by means of two-dimensional electrophoresis (2-DE coupled with Mass Spectrometry analysis, useful for identifying potential markers of plaque presence and vulnerability. The adopted method allowed obtaining reproducible 2-DE maps of exchangeable apolipoproteins from VLDL, LDL, and HDL. Twenty-three protein isoforms were identified by peptide mass fingerprinting analysis. Differential proteomic analysis allowed for identifying increased levels of acute-phase serum amyloid A protein (AP SAA in all lipoprotein fractions, especially in LDL from atherosclerotic patients. Results have been confirmed by western blotting analysis on each lipoprotein fraction using apo AI levels for data normalization. The higher levels of AP SAA found in patients suggest a role of LDL as AP SAA carrier into the subendothelial space of artery wall, where AP SAA accumulates and may exert noxious effects.

  20. Measurement of Collagen and Smooth Muscle Cell Content in Atherosclerotic Plaques Using Polarization-Sensitive Optical Coherence Tomography

    Science.gov (United States)

    Nadkarni, Seemantini K.; Pierce, Mark C.; Park, B. Hyle; de Boer, Johannes F.; Whittaker, Peter; Bouma, Brett E.; Bressner, Jason E.; Halpern, Elkan; Houser, Stuart L.; Tearney, Guillermo J.

    2009-01-01

    Objectives The purpose of this study was to investigate the measurement of collagen and smooth muscle cell (SMC) content in atherosclerotic plaques using polarization-sensitive optical coherence tomography (PSOCT). Background A method capable of evaluating plaque collagen content and SMC density can provide a measure of the mechanical fidelity of the fibrous cap and can enable the identification of high-risk lesions. Optical coherence tomography has been demonstrated to provide cross-sectional images of tissue microstructure with a resolution of 10 µm. A recently developed technique, PSOCT measures birefringence, a material property that is elevated in tissues such as collagen and SMCs. Methods We acquired PSOCT images of 87 aortic plaques obtained from 20 human cadavers. Spatially averaged PSOCT birefringence, Φ, was measured and compared with plaque collagen and SMC content, quantified morphometrically by picrosirius red and smooth muscle actin staining at the corresponding locations. Results There was a high positive correlation between PSOCT measurements of Φ and total collagen content in all plaques (r = 0.67, p < 0.001) and in fibrous caps of necrotic core fibroatheromas (r = 0.68, p < 0.001). Polarization-sensitive optical coherence tomography measurements of Φ demonstrated a strong positive correlation with thick collagen fiber content (r = 0.76, p < 0.001) and SMC density (r = 0.74, p < 0.01). Conclusions Our results demonstrate that PSOCT enables the measurement of birefringence in plaques and in fibrous caps of necrotic core fibroatheromas. Given its potential to evaluate collagen content, collagen fiber thickness, and SMC density, we anticipate that PSOCT will significantly improve our ability to evaluate plaque stability in patients. PMID:17397678

  1. [Characterization of atherosclerotic plaque in patients with unstable angina pectoris and stable angina pectoris by optical coherence tomography].

    Science.gov (United States)

    Chen, Bu-xing; Ma, Feng-yun; Luo, Wei; Ruan, Jian-hong; Zhao, Xi-zhe; Xie, Wen-li; Sun, Shu-hong; Guo, Xu-mei; Wang, Feng; Tian, Ting; Chu, Xiao-wen

    2009-05-01

    To compare the characterization of coronary atherosclerotic plaques in patients with unstable angina pectoris (UAP) and stable angina pectoris (SAP) by optical coherence tomography (OCT). OCT was performed in 47 patients (23 UAP and 24 SAP) undergoing coronary angiography. Lipid-rich plaque (defined by > or = 2 quadrants of the cross-section area), thin cap fibroatheroma (TCFA), thickness of fibrous cap, plaque rupture, calcification and thrombus visualized by OCT were compared between UAP and SAP patients. OCT imaging was successfully in 44 out of 47 patients (22 UAP, 22 SAP). Proportion of lipid-rich plaques was similar between UAP and SAP groups [91% (20/22) vs. 73% (16/22), P = 0.741]. The minimum thickness of fibrous cap in the UAP group was significantly thinner than that in SAP group [(69.5 +/- 34.7) microm vs. (141.1 +/- 68.5) microm, P = 0.000] and the rate of fibrous cap erosion in the UAP group was significantly higher than that in the SAP group [59% (13/22) vs. 9% (2/22), P = 0.000]. Percents of TCFA [73% (16/22) vs. 14% (3/22), P = 0.000] and plaque rupture [50% (11/22) vs. 9% (2/22), P = 0.003] were significantly higher in UAP group compared those in SAP group. Incidence of thrombus and calcification were similar between two groups. OCT imaging can clearly define plaque characterization of coronary atherosclerosis. UAP patients have thinner fibrous cap, higher incidences of fibrous cap erosion, plaque rupture and TCFA compared patients with SAP.

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

    DEFF Research Database (Denmark)

    Fumagalli, Stefano; Perego, Carlo; Zangari, Rosalia

    2017-01-01

    to plaque vulnerability. Ficolins and MBL were found both in plaques' necrotic core and tunica media. Patients with vulnerable plaques showed decreased plasma levels and intraplaque deposition of ficolin-2. Symptomatic patients experiencing a transient ischemic attack had lower plasma levels of ficolin-1...

  3. Carotid plaque segmentation from three-dimensional ultrasound images by direct three-dimensional sparse field level-set optimization.

    Science.gov (United States)

    Cheng, Jieyu; Chen, Yimin; Yu, Yanyan; Chiu, Bernard

    2018-03-01

    Total plaque volume (TPV) measured from 3D carotid ultrasound has been shown to be able to predict cardiovascular events and is sensitive in detecting treatment effects. Manual plaque segmentation was performed in previous studies to quantify TPV, but is tedious, requires long training times and is prone to observer variability. This article introduces the first 3D direct volume-based level-set algorithm to segment plaques from 3D carotid ultrasound images. The plaque surfaces were first initialized based on the lumen and outer wall boundaries generated by a previously described semi-automatic algorithm and then deformed by a direct three-dimensional sparse field level-set algorithm, which enforced the longitudinal continuity of the segmented plaque surfaces. This is a marked advantage as compared to a previously proposed 2D slice-by-slice plaque segmentation method. In plaque boundary initialization, the previous technique performed a search on lines connecting corresponding point pairs of the outer wall and lumen boundaries. A limitation of this initialization strategy was that an inaccurate initial plaque boundary would be generated if the plaque was not enclosed entirely by the wall and lumen boundaries. A mechanism is proposed to extend the search range in order to capture the entire plaque if the outer wall boundary lies on a weak edge in the 3D ultrasound image. The proposed method was compared with the previously described 2D slice-by-slice plaque segmentation method in 26 three-dimensional carotid ultrasound images containing 27 plaques with volumes ranging from 12.5 to 450.0 mm 3 . The manually segmented plaque boundaries serve as the surrogate gold standard. Segmentation accuracy was quantified by volume-, area- and distance-based metrics, including absolute plaque volume difference (|ΔPV|), Dice similarity coefficient (DSC), mean and maximum absolute distance (MAD and MAXD). The proposed direct 3D plaque segmentation algorithm was associated with a

  4. Regression and shift in composition of coronary atherosclerotic plaques by pioglitazone: insight from an intravascular ultrasound analysis.

    Science.gov (United States)

    Clementi, Fabrizio; Di Luozzo, Marco; Mango, Ruggiero; Luciani, Giulio; Trivisonno, Antonio; Pizzuto, Francesco; Martuscelli, Eugenio; Mehta, Jawahar L; Romeo, Francesco

    2009-03-01

    Plaque reduction with the use of pioglitazone and statin combination therapy has been observed in carotid plaque. We sought to investigate the effect of combination therapy with statins and pioglitazone on coronary plaque regression and composition with the use of intravascular ultrasound (IVUS) and intravascular ultrasound-virtual histology (IVUS-VH). We analysed 29 plaques in 25 diabetic patients with angiographic evidence of nonsignificant coronary lesions with IVUS-VH. Patients were treated with 80 mg of atorvastatin and 30 mg of pioglitazone daily for 6 months. After 6 months of therapy, IVUS-VH of each lesion was reacquired. Mean elastic external membrane volume was significantly reduced between baseline and follow-up (343.9 vs. 320.5 mm; P < 0.05) as was mean total atheroma volume (179.3 vs. 166.6 mm; P < 0.05). Change in total atheroma volume showed a 6.3% mean reduction. Areas of fibrous tissue, fibrolipidic tissue and calcium decreased over the 6 months of follow-up, although not significantly. On the other hand, the necrotic core increased from 9 to 14% (P < 0.05). Our data demonstrated that atorvastatin/pioglitazone association is able to induce significant regression of coronary atherosclerosis, acting on plaque composition. Our findings are preliminary results and will be confirmed in an ongoing randomized placebo-controlled multicenter trial (PIPER; Pioglitazone for Prevention of Restenosis in Diabetics with Complex Lesion; trial registration: clinical trials.gov. Identifier: NCT 00376870).

  5. Optimal MR Plaque Imaging for Cervical Carotid Artery Stenosis in Predicting the Development of Microembolic Signals during Exposure of Carotid Arteries in Endarterectomy: Comparison of 4 T1-Weighted Imaging Techniques.

    Science.gov (United States)

    Sato, Y; Ogasawara, K; Narumi, S; Sasaki, M; Saito, A; Tsushima, E; Namba, T; Kobayashi, M; Yoshida, K; Terayama, Y; Ogawa, A

    2016-06-01

    Preoperative identification of plaque vulnerability may allow improved risk stratification for patients considered for carotid endarterectomy. The present study aimed to determine which plaque imaging technique, cardiac-gated black-blood fast spin-echo, magnetization-prepared rapid acquisition of gradient echo, source image of 3D time-of-flight MR angiography, or noncardiac-gated spin-echo, most accurately predicts development of microembolic signals during exposure of carotid arteries in carotid endarterectomy. Eighty patients with ICA stenosis (≥70%) underwent the 4 sequences of preoperative MR plaque imaging of the affected carotid bifurcation and then carotid endarterectomy under transcranial Doppler monitoring of microembolic signals in the ipsilateral middle cerebral artery. The contrast ratio of the carotid plaque was calculated by dividing plaque signal intensity by sternocleidomastoid muscle signal intensity. Microembolic signals during exposure of carotid arteries were detected in 23 patients (29%), 3 of whom developed new neurologic deficits postoperatively. Those deficits remained at 24 hours after surgery in only 1 patient. The area under the receiver operating characteristic curve to discriminate between the presence and absence of microembolic signals during exposure of the carotid arteries was significantly greater with nongated spin-echo than with black-blood fast spin-echo (difference between areas, 0.258; P exposure of the carotid arteries in carotid endarterectomy more accurately than other MR plaque imaging techniques. © 2016 by American Journal of Neuroradiology.

  6. Assessment of carotid plaque composition using fast-kV switching dual-energy CT with gemstone detector: comparison with extracorporeal and virtual histology-intravascular ultrasound

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    Shinohara, Yuki; Kuya, Keita; Ohta, Yasutoshi; Fujii, Shinya; Ogawa, Toshihide [Tottori University, Division of Radiology, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Yonago (Japan); Sakamoto, Makoto; Watanabe, Takashi [Tottori University, Division of Neurosurgery, Department of Neurological Sciences, Faculty of Medicine, Yonago (Japan); Kishimoto, Junichi; Iwata, Naoki [Tottori University Hospital, Division of Clinical Radiology, Yonago (Japan)

    2015-09-15

    The present study compares the applicability of CT carotid plaque imaging using effective Z maps using gemstone spectral imaging (GSI) with that of conventional extracorporeal carotid ultrasound (US) and virtual histology-intravascular ultrasound (VH-IVUS). We assessed stenosis in 31 carotid arteries of 30 patients. All patients underwent carotid CTA using GSI (Discovery CT750 HD, GE Healthcare). US and IVUS were examined with 25 and 8 vessels, respectively. We compared the effective Z values at noncalcified carotid plaque with the plaque components identified by US. We defined the plaque with low or low to iso intensity on US as vulnerable plaque and the plaque with iso, iso to high, and high intensity on US as stable plaque. We also performed visual assessment of color-coded effective Z maps in comparison with VH-IVUS and compared effective Z values with plaque components generated by VH-IVUS. The effective Z values at noncalcified carotid plaque were significantly lower for a group with vulnerable plaque, than with stable plaque on US (p < 0.05). Receiver operating curve analysis showed that AUC of effective Z values was 0.882 concerning the differentiation of these two groups on US. The interpretation of color-coded effective Z maps was essentially compatible with that of VH-IVUS for carotid plaque in all vessels. Effective Z values at noncalcified plaque showed significant negative correlation with the areas of fibro-fatty components generated by VH-IVUS (ρ = -0.874, p < 0.05). Effective Z maps generated by GSI can detect vulnerable carotid plaque materials. (orig.)

  7. Assessment of carotid plaque composition using fast-kV switching dual-energy CT with gemstone detector: comparison with extracorporeal and virtual histology-intravascular ultrasound

    International Nuclear Information System (INIS)

    Shinohara, Yuki; Kuya, Keita; Ohta, Yasutoshi; Fujii, Shinya; Ogawa, Toshihide; Sakamoto, Makoto; Watanabe, Takashi; Kishimoto, Junichi; Iwata, Naoki

    2015-01-01

    The present study compares the applicability of CT carotid plaque imaging using effective Z maps using gemstone spectral imaging (GSI) with that of conventional extracorporeal carotid ultrasound (US) and virtual histology-intravascular ultrasound (VH-IVUS). We assessed stenosis in 31 carotid arteries of 30 patients. All patients underwent carotid CTA using GSI (Discovery CT750 HD, GE Healthcare). US and IVUS were examined with 25 and 8 vessels, respectively. We compared the effective Z values at noncalcified carotid plaque with the plaque components identified by US. We defined the plaque with low or low to iso intensity on US as vulnerable plaque and the plaque with iso, iso to high, and high intensity on US as stable plaque. We also performed visual assessment of color-coded effective Z maps in comparison with VH-IVUS and compared effective Z values with plaque components generated by VH-IVUS. The effective Z values at noncalcified carotid plaque were significantly lower for a group with vulnerable plaque, than with stable plaque on US (p < 0.05). Receiver operating curve analysis showed that AUC of effective Z values was 0.882 concerning the differentiation of these two groups on US. The interpretation of color-coded effective Z maps was essentially compatible with that of VH-IVUS for carotid plaque in all vessels. Effective Z values at noncalcified plaque showed significant negative correlation with the areas of fibro-fatty components generated by VH-IVUS (ρ = -0.874, p < 0.05). Effective Z maps generated by GSI can detect vulnerable carotid plaque materials. (orig.)

  8. Endothelial dysfunction is associated with carotid plaque: a cross-sectional study from the population based Northern Manhattan Study

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    Boden-Albala Bernadette

    2006-08-01

    Full Text Available Abstract Background Impaired vascular function occurs early in atherogenesis. Brachial flow mediated dilatation (FMD is a non-invasive measure of vascular function and may be an important marker of preclinical atherosclerosis. Data on the association between FMD and carotid plaque in multi-ethnic populations are limited. The objective of this study was to determine whether endothelial dysfunction is independently associated with carotid plaque in a community of northern Manhattan. Methods In the population-based Northern Manhattan Study (NOMAS, high-resolution B-mode ultrasound images of the brachial and carotid arteries were obtained in 643 stroke-free subjects (mean age 66 years; 55% women; 65% Caribbean-Hispanic, 17% African-American, 16% Caucasian. Brachial FMD was measured during reactive hyperemia. Maximum carotid plaque thickness (MCPT was measured at the peak plaque prominence. Results The mean brachial FMD was 5.78 ± 3.83 %. Carotid plaque was present in 339 (53% subjects. The mean MCPT was 1.68 ± 0.82 mm, and the 75th percentile was 2.0 mm. Reduced FMD was significantly associated with increased MCPT. After adjusting for demographics, vascular risk factors, and education, each percent of FMD decrease was associated with a significant 0.02 mm increase in MCPT (p = 0.028. In a dichotomous adjusted model, blunted FMD was associated with an increased risk of MCPT ≥ 2.0 mm (OR, 1.11 for every 1% decrease in FMD; 95% CI, 1.03–1.19. Conclusion Decreased brachial FMD is independently associated with carotid plaque. Non-invasive evaluation of endothelial dysfunction may be a useful marker of preclinical atherosclerosis and help to individualize cardiovascular risk assessment beyond traditional risk factors.

  9. Expression of lipoprotein-associated phospholipase A2 in carotid artery plaques predicts long-term cardiac outcome

    Science.gov (United States)

    Herrmann, Joerg; Mannheim, Dallit; Wohlert, Christine; Versari, Daniele; Meyer, Fredric B.; McConnell, Joseph P.; Gössl, Mario; Lerman, Lilach O.; Lerman, Amir

    2009-01-01

    Aims The aim was to test the hypothesis that carotid artery plaque expression of lipoprotein-associated phospholipase A2 (Lp-PLA2) predicts cardiac events. Methods and results Prospective cohort study of 162 consecutive patients undergoing elective carotid endarterectomy. Lipoprotein-associated phospholipase A2 content was quantified by immunoblotting and lysophosphatidylcholine (lysoPC) by liquid chromatography tandem mass spectrometry. Additional biomolecular profiling by immunoblotting included C-reactive protein, p67phox, and matrix metalloproteinase-2 and -9. Macrophage plaque content was determined by quantitative immunostaining, plaque collagen content by quantitative Sirius red staining. Follow-up for cardiac death and non-fatal acute myocardial infarction was accomplished over a period of 48 ± 14 months. Expression of Lp-PLA2 and lysoPC was higher in carotid plaques of patients with than without cardiac events [median 1.6 (25th, 75th percentile 0.9, 2.5) vs. 0.8 (0.5, 2.0), P = 0.01 and 413 (281, 443) vs. 226 (96, 351) mmol/L, P = 0.03]. Smoking and point increase in carotid Lp-PLA2 expression but no other traditional cardiovascular risk factor, histological or molecular marker remained predictive of cardiac events in the multivariate Cox proportional hazard analyses [HR 3.65 (1.36–9.83), P = 0.01 and HR 1.34 (1.01–1.77), P = 0.039]. Carotid plaque Lp-PLA2 expression above the median constituted a more than three times higher risk for cardiac events [HR 3.39 (1.13–10.17), P = 0.03]. Conclusion Lipoprotein-associated phospholipase A2 expression in carotid artery plaques is a predictor of long-term cardiac outcome. The current study supports the concept of atherosclerosis as a systemic disease with multi-focal complications and personalized medicine. PMID:19689974

  10. Expression of lipoprotein-associated phospholipase A(2) in carotid artery plaques predicts long-term cardiac outcome.

    Science.gov (United States)

    Herrmann, Joerg; Mannheim, Dallit; Wohlert, Christine; Versari, Daniele; Meyer, Fredric B; McConnell, Joseph P; Gössl, Mario; Lerman, Lilach O; Lerman, Amir

    2009-12-01

    The aim was to test the hypothesis that carotid artery plaque expression of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) predicts cardiac events. Prospective cohort study of 162 consecutive patients undergoing elective carotid endarterectomy. Lipoprotein-associated phospholipase A(2) content was quantified by immunoblotting and lysophosphatidylcholine (lysoPC) by liquid chromatography tandem mass spectrometry. Additional biomolecular profiling by immunoblotting included C-reactive protein, p67phox, and matrix metalloproteinase-2 and -9. Macrophage plaque content was determined by quantitative immunostaining, plaque collagen content by quantitative Sirius red staining. Follow-up for cardiac death and non-fatal acute myocardial infarction was accomplished over a period of 48 +/- 14 months. Expression of Lp-PLA(2) and lysoPC was higher in carotid plaques of patients with than without cardiac events [median 1.6 (25th, 75th percentile 0.9, 2.5) vs. 0.8 (0.5, 2.0), P = 0.01 and 413 (281, 443) vs. 226 (96, 351) mmol/L, P = 0.03]. Smoking and point increase in carotid Lp-PLA(2) expression but no other traditional cardiovascular risk factor, histological or molecular marker remained predictive of cardiac events in the multivariate Cox proportional hazard analyses [HR 3.65 (1.36-9.83), P = 0.01 and HR 1.34 (1.01-1.77), P = 0.039]. Carotid plaque Lp-PLA(2) expression above the median constituted a more than three times higher risk for cardiac events [HR 3.39 (1.13-10.17), P = 0.03]. Lipoprotein-associated phospholipase A(2) expression in carotid artery plaques is a predictor of long-term cardiac outcome. The current study supports the concept of atherosclerosis as a systemic disease with multi-focal complications and personalized medicine.

  11. Carotid plaque stabilization induced by the supplement association Pycnogenol® and centella asiatica (Centellicum®).

    Science.gov (United States)

    Luzzi, Roberta; Belcaro, Gianni; Ippolito, Edmondo

    2016-12-01

    Aim of this registry study was the evaluation of the stability of carotid plaques by ultrasound in asymptomatic subjects with high oxidative stress following supplementation with a combination of the extract from bark of Pinus pinaster, Pycnogenol®, with an extract from Centella asiatica leaves, Centellicum®. 50 patients, mean age 61.5 years, with carotid plaques (<50% stenosis) and high oxidative stress were included in this 3 months registry study. 26 patients received the combination of Pycnogenol® and Centellicum® and standard management, a control group received standard management only. The 2 groups were comparable. The combination of Pycnogenol® and Centellicum® reduced significantly (p<0.05) plaque height and length as well as the number of plaques relative to controls. The plaque stability index, based on the echogenicity in the ultrasound picture of the "white" components of the plaque, increased significantly (p<0.01) in the verum group, no changes were observed in the controls. Plasma free radicals were significantly (p<0.05) decreased by the combination product, whereas the levels of plasma free radicals remained unchanged in the control group. No unwanted effects or abnormal laboratory tests were recorded. This registry study revealed a significant increase in stability of plaques, indicated by an enhanced density of the plaques, following supplementation with the combination of Pycnogenol® and Centellicum®. As size and number of plaques was simultaneously reduced, the combination of the two plant extracts could be a safe option for prevention of cardiovascular events for patients with carotid plaques.

  12. [Collagen fiber pathology in atherosclerotic plaques of the coronary arteries in ischemic heart disease].

    Science.gov (United States)

    Zhdanov, V S; Veselova, S P; Drobkova, I P; Galakhov, I E

    2011-01-01

    Structure-metabolic changes of collagen fibers (CF) in atherosclerosis plaques of the coronary arteries in the conditions of ischemic heart disease (IHD) have been studied. Segments of the coronary arteries were received from 68 men after a coronary artery bypass grafting. CF was study with using of the Van Gieson's and the Masson's methods. Histologic slices were studied by polarization microscopy. The atherosclerosis plaques with IHD were notable for lipidosis of CF. We've suspected lipidosis of CF is a crucial factor for the development of atherosclerosis plaques instability. Evident lipidosis of CF was attended with destructive changes probably resulted in accumulation of atheromatous mass in atherosclerosis plaques.

  13. Study on the correlation between serum Angptl2 level and carotid plaque nature in Type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Mao-Ji La

    2016-06-01

    Full Text Available Objective: To analyze the correlation between serum Angptl2 level and carotid plaque nature in Type 2 diabetes. Methods: 118 cases of Type 2 diabetes patients hospitalized in our hospital from August 2012 to December 2015 were the subjects of observation group, were accompanied with different degree of carotid plaque through B ultrasound and CT coronary arterial angiography examination, and were divided into unstable plaque group (n=56 and stable plaque group (n=62 according to the degree of plaque, and 97 cases of patients with Type 2 diabetes alone (not complicated with carotid plaque who received blood glucose regulation treatment in our hospital during the same period were the control group. Serum Angptl2 levels and the values of carotid plaque nature-related indexes of all groups were detected, and the correlation between the two was further analyzed. Results: Serum Angptl2 level of observation group was significantly higher than that of control group, and serum Angptl2 level of unstable plaque group was higher than that of stable plaque group; serum Fbg, HbA1c and bigET-1 values of observation group were higher than those of control group while DBIL and RHI values were lower than those of control group; serum cystatin c and visfatin values of observation group were higher than those of control group while ApoA1 and MPO values were lower than those of control group; serum ACA, MIF, sCD40L, PAPP-A, CXCR16, t-HCY and D-dimer values of observation group were higher than those of control group; serum Angptl2 level was directly proportional to Fng, HbA1c, bigET-1, cystatin c, ApoA1, visfatin, ACA, MIF, sCD40L, PAPP-A, CXCR16, t-HCY and D-dimer levels, and inversely proportional to DBIL, RHI and MPO values. Conclusion: Angptl2 level is significantly abnormal in Type 2 diabetes patients with carotid plaque, has direct correlation with plaque nature-related indexes, and is the reliable index to judge patients’ condition and predict the outcome.

  14. Relationship between serum hypoxia-inducible factor-1α and carotid plaque in patients with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    E Weiqin; Shi Bimin

    2012-01-01

    Objective: To observe the changes of type 2 diabetes mellitus (T2DM) patients' serum hypoxia inducible factor-1α (HIF-1α), and evaluate the relationship between serum HIF-1α and vascular lesions of atherosclerosis. Methods: The serum level of HIF-1α in 32 T2DM with carotid plaques (T2DM+CP group), 24 T2DM without macrovascular complications (T2DM group), and 24 controls was studied with ELISA method. Results: The serum HIF-1α level in T2DM with and without carotid plaque group was significantly higher than that in the controls (all P<0.01). Furthermore, among T2DM, the level of HIF-1α was higher in patients with carotid plaque than that without carotid plaque (P<0.05) . The serum HIF-1α was positively correlated with fasting plasma glucose, HbAlc and HOMA-IR (all P<0.05). Multiple linear stepwise regression analysis showed that HbAlc was the independent determinants of HIF-1α. Conclusion: High level of serum HIF-1α in T2DM patients concerns with blood glucose and insulin resistance, which plays an important role in the development of macrovascular complications. (authors)

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

    Science.gov (United States)

    Huang, Xueying; Teng, Zhongzhao; Canton, Gador; Ferguson, Marina; Yuan, Chun; Tang, Dalin

    2010-12-31

    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). 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. 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 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. 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 additional stress indicators for image-based vulnerability assessment.

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

    Directory of Open Access Journals (Sweden)

    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

  17. Correlation of fibrinogen, C-reactive protein and homocysteine with the carotid vulnerable plaque in patients with large artery atherosclerosis stroke

    Directory of Open Access Journals (Sweden)

    Jing LI

    2017-02-01

    Full Text Available Objective To explore the correlation between the serum levels of fibrinogen (FIB, C-reactive protein (CRP and homocysteine (Hcy with the carotid vulnerable plaque in patients with large artery atherosclerosis (LAA stroke. Methods The patients with acute ischemic stroke (AIS admitted to the Department of Neurology in The Second Hospital of Lanzhou University from Mar. 2014 to Feb. 2015 were collected continuously, and 273 patients with anterior circulation of LAA stroke were selected based on the TOAST classification. These patients were classified as non-plaque group (n=84, stable plaque group (n=42 and vulnerable plaque group (n=147 according to the carotid ultrasonography examination. Another 182 patients without carotid disease of non-stroke selected simultaneously from our department were regarded as controls. The 19 demographic parameters and hematological indices were compared among the four groups. The logistic regression was used to screen the independent risk factors for carotid vulnerable plaque in LAA stroke patients. The Spearman rank correlation was performed to analyze the correlation between the carotid plaque vulnerability in LAA stroke patients with all the indicators. Results The levels of FIB, CRP and Hcy in the four groups showed statistically significant differences (P<0.05. The multivariate logistic regression analysis revealed that FIB (OR=1.408, 95% CI 1.028-1.927, P=0.033 was the independent risk factor for carotid vulnerable plaque in patients with LAA stroke. The Spearman correlation analysis presented a positive correlation between carotid plaque vulnerability in LAA stroke patients with FIB (r=0.292; P=0.000 and Hcy (r=0.172; P=0.000. Conclusions The serum FIB and Hcy levels may be the meaningful biomarkers to predict the vulnerable carotid plaque in patients with LAA stroke. The serum level of CRP has no obvious correlation with carotid plaque vulnerability in LAA stroke patients. DOI: 10.11855/j.issn.0577-7402.2017.01.08

  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)

    Hu Jian; Lu Lin; Wu Liqun; Zhang Qi; Ding Feghua; Yang Zhenkun; Zhang Ruiyan; Zhang Jiansheng; Shen Weifeng

    2009-01-01

    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. Quantification of carotid artery plaque stability with multiple region of interest based ultrasound strain indices and relationship with cognition

    Science.gov (United States)

    Meshram, N. H.; Varghese, T.; Mitchell, C. C.; Jackson, D. C.; Wilbrand, S. M.; Hermann, B. P.; Dempsey, R. J.

    2017-08-01

    Vulnerability and instability in carotid artery plaque has been assessed based on strain variations using noninvasive ultrasound imaging. We previously demonstrated that carotid plaques with higher strain indices in a region of interest (ROI) correlated to patients with lower cognition, probably due to cerebrovascular emboli arising from these unstable plaques. This work attempts to characterize the strain distribution throughout the entire plaque region instead of being restricted to a single localized ROI. Multiple ROIs are selected within the entire plaque region, based on thresholds determined by the maximum and average strains in the entire plaque, enabling generation of additional relevant strain indices. Ultrasound strain imaging of carotid plaques, was performed on 60 human patients using an 18L6 transducer coupled to a Siemens Acuson S2000 system to acquire radiofrequency data over several cardiac cycles. Patients also underwent a battery of neuropsychological tests under a protocol based on National Institute of Neurological Disorders and Stroke and Canadian Stroke Network guidelines. Correlation of strain indices with composite cognitive index of executive function revealed a negative association relating high strain to poor cognition. Patients grouped into high and low cognition groups were then classified using these additional strain indices. One of our newer indices, namely the average L  -  1 norm with plaque (AL1NWP) presented with significantly improved correlation with executive function when compared to our previously reported maximum accumulated strain indices. An optimal combination of three of the new indices generated classifiers of patient cognition with an area under the curve (AUC) of 0.880, 0.921 and 0.905 for all (n  =  60), symptomatic (n  =  33) and asymptomatic patients (n  =  27) whereas classifiers using maximum accumulated strain indices alone provided AUC values of 0.817, 0.815 and 0

  20. Cell proliferation in the atherosclerotic plaques of cholesterol-fed rabbits

    International Nuclear Information System (INIS)

    Cavallero, C.; Tondo, U. di; Mingazinni, P.L.; Nicosia, R.; Pericoli, M.N.; Sarti, P.; Spagnoli, L.G.; Villaschi, S.

    1976-01-01

    Tritiated thymidine radioautography was employed to study the effect of cortisol and other glucocorticoids on cellular proliferation in the aorta and pulmonary artery of rabbits with cholesterol atherosclerosis. Labelled cell counts showed that glucocorticoids, even after one day and at a relatively low dose, decrease sharply the deoxyribonucleic acid synthesis in the intimal plaques. The hormonal influence on [ 3 H] thymidine uptake seems to be a dose-dependent process. The relative potency of these steroids in inhibiting DNA synthesis in the plaques parallels closely their anti-inflammatory effectiveness. Conversely mineralocorticoids, including aldosterone and deoxycorticosterone, increase the rate of DNA synthesis in the plaques. It is concluded that the anti-atherogenic effect of glucocorticoids on cholesterol-fed rabbits may be due, at least partly, to the inhibitory effect of these steroids on the DNA synthesis of the cellular components of the intimal plaques

  1. Relation between TLR4/NF-κB signaling pathway activation by 27-hydroxycholesterol and 4-hydroxynonenal, and atherosclerotic plaque instability

    Science.gov (United States)

    Gargiulo, Simona; Gamba, Paola; Testa, Gabriella; Rossin, Daniela; Biasi, Fiorella; Poli, Giuseppe; Leonarduzzi, Gabriella

    2015-01-01

    It is now thought that atherosclerosis, although due to increased plasma lipids, is mainly the consequence of a complicated inflammatory process, with immune responses at the different stages of plaque development. Increasing evidence points to a significant role of Toll-like receptor 4 (TLR4), a key player in innate immunity, in the pathogenesis of atherosclerosis. This study aimed to determine the effects on TLR4 activation of two reactive oxidized lipids carried by oxidized low-density lipoproteins, the oxysterol 27-hydroxycholesterol (27-OH) and the aldehyde 4-hydroxynonenal (HNE), both of which accumulate in atherosclerotic plaques and play a key role in the pathogenesis of atherosclerosis. Secondarily, it examined their potential involvement in mediating inflammation and extracellular matrix degradation, the hallmarks of high-risk atherosclerotic unstable plaques. In human promonocytic U937 cells, both 27-OH and HNE were found to enhance cell release of IL-8, IL-1β, and TNF-α and to upregulate matrix metalloproteinase-9 (MMP-9) via TLR4/NF-κB-dependent pathway; these actions may sustain the inflammatory response and matrix degradation that lead to atherosclerotic plaque instability and to their rupture. Using specific antibodies, it was also demonstrated that these inflammatory cytokines increase MMP-9 upregulation, thus enhancing the release of this matrix-degrading enzyme by macrophage cells and contributing to plaque instability. These innovative results suggest that, by accumulating in atherosclerotic plaques, the two oxidized lipids may contribute to plaque instability and rupture. They appear to do so by sustaining the release of inflammatory molecules and MMP-9 by inflammatory and immune cells, for example, macrophages, through activation of TLR4 and its NF-κB downstream signaling. PMID:25757594

  2. Histological patterns of atherosclerotic plaques in unstable angina patients vary according to clinical presentation

    OpenAIRE

    Mann, J; Kaski, J; Pereira, W; Arie, S; Ramires, J; Pileggi, F

    1998-01-01

    Background—Unstable angina is a heterogeneous clinical syndrome. The diverse clinical presentations of unstable angina may reflect different pathogenic mechanisms within the plaque.
Objective—To investigate the cellular constituents of culprit coronary atheromatous plaques in patients with stable angina pectoris and patients with diverse clinical presentations of unstable angina.
Methods—48 patients who underwent coronary atherectomy for management of ischaemic heart disease: 23 had stable an...

  3. 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

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

    International Nuclear Information System (INIS)

    Ma Xiaohai; Zhang Zhaoqi; Zhao Lei; Zhao Quanming; Shang Jianfeng; Feng Tingting; Zeng Conghe

    2011-01-01

    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), T 1 WI, T 2 WI and post contrast T 1 WI. 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, P 2 vs. (8.93±5.36) mm 2 , P<0.01]. Conclusion: MRI is useful tool to determine the thrombosis and plaque rupture in atherosclerotic rabbit model. (authors)

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Intravascular detection of microvessel infiltration in atherosclerotic plaques: An intraluminal extension of acoustic angiography

    Science.gov (United States)

    Martin, K. Heath

    Cardiovascular disease is the leading cause of death worldwide, surpassing both stroke and cancer related mortality with 17.5 million deaths in 2014 alone. Atherosclerosis is the build-up of fatty deposits within arteries and is responsible for the majority of cardiovascular related deaths. Over the past decade, research in atherosclerosis has identified that a key limitation in the appropriate management of the disease is detecting and identifying dangerous fatty plaque build-ups before they dislodge and cause major cardiovascular events, such as embolisms, stroke, or myocardial infarctions. It has been noted that plaques vulnerable to rupture have several key features that may be used to distinguish them from asymptomatic plaques. One key identifier of a dangerous plaque is the presence of blood flow within the plaque itself since this is an indicator of growth and instability of the plaque. Recently, a superharmonic imaging method known as "acoustic angiography" has been shown to resolve microvasculature with unprecedented quality and could be a possible method of detecting blood vessel infiltration within these plaques. This dissertation describes the material and methods used to move the application of "acoustic angiography" to a reduced form factor typical of intravascular catheters and to demonstrate its ability to detect microvasculature. The implementation of this approach is described in terms of the contrast agents used to generate superharmonic signals, the dual-frequency transducers to image them, and the hardware needed to operate them in order to establish how these design choices can impact the quality of the images produced. Furthermore, this dissertation demonstrates how image processing methods such as adaptive windowing or automated sound speed correction can further enhance image quality of vascular targets. The results of these chapters show how acoustic angiography may be optimized using engineering considerations both in signal acquisition

  7. 2-D Versus 3-D Cross-Correlation-Based Radial and Circumferential Strain Estimation Using Multiplane 2-D Ultrafast Ultrasound in a 3-D Atherosclerotic Carotid Artery Model.

    Science.gov (United States)

    Fekkes, Stein; Swillens, Abigail E S; Hansen, Hendrik H G; Saris, Anne E C M; Nillesen, Maartje M; Iannaccone, Francesco; Segers, Patrick; de Korte, Chris L

    2016-10-01

    Three-dimensional (3-D) strain estimation might improve the detection and localization of high strain regions in the carotid artery (CA) for identification of vulnerable plaques. This paper compares 2-D versus 3-D displacement estimation in terms of radial and circumferential strain using simulated ultrasound (US) images of a patient-specific 3-D atherosclerotic CA model at the bifurcation embedded in surrounding tissue generated with ABAQUS software. Global longitudinal motion was superimposed to the model based on the literature data. A Philips L11-3 linear array transducer was simulated, which transmitted plane waves at three alternating angles at a pulse repetition rate of 10 kHz. Interframe (IF) radio-frequency US data were simulated in Field II for 191 equally spaced longitudinal positions of the internal CA. Accumulated radial and circumferential displacements were estimated using tracking of the IF displacements estimated by a two-step normalized cross-correlation method and displacement compounding. Least-squares strain estimation was performed to determine accumulated radial and circumferential strain. The performance of the 2-D and 3-D methods was compared by calculating the root-mean-squared error of the estimated strains with respect to the reference strains obtained from the model. More accurate strain images were obtained using the 3-D displacement estimation for the entire cardiac cycle. The 3-D technique clearly outperformed the 2-D technique in phases with high IF longitudinal motion. In fact, the large IF longitudinal motion rendered it impossible to accurately track the tissue and cumulate strains over the entire cardiac cycle with the 2-D technique.

  8. The time window of MRI of murine atherosclerotic plaques after administration of CB2 receptor targeted micelles: inter-scan variability and relation between plaque signal intensity increase and gadolinium content of inversion recovery prepared versus non-prepared fast spin echo

    NARCIS (Netherlands)

    te Boekhorst, B. C. M.; Bovens, S. M.; van de Kolk, C. W. A.; Cramer, M. J. M.; Doevendans, P. A. F. M.; ten Hove, M.; van der Weerd, L.; Poelmann, R.; Strijkers, G. J.; Pasterkamp, G.; van Echteld, C. J. A.

    2010-01-01

    Single fast spin echo scans covering limited time frames are mostly used for contrast-enhanced MRI of atherosclerotic plaque biomarkers. Knowledge on inter-scan variability of the normalized enhancement ratio of plaque (NER(plaque)) and relation between NER(plaque) and gadolinium content for

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

    International Nuclear Information System (INIS)

    Song Qiong; Xia Liming; Wang Chengyuan; Hu Junwu; Feng Dingyi; Zou Mingli

    2006-01-01

    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 T 1 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 T 1 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)

  10. Comparison of grey scale median (GSM) measurement in ultrasound images of human carotid plaques using two different softwares.

    Science.gov (United States)

    Östling, Gerd; Persson, Margaretha; Hedblad, Bo; Gonçalves, Isabel

    2013-11-01

    Grey scale median (GSM) measured on ultrasound images of carotid plaques has been used for several years now in research to find the vulnerable plaque. Centres have used different software and also different methods for GSM measurement. This has resulted in a wide range of GSM values and cut-off values for the detection of the vulnerable plaque. The aim of this study was to compare the values obtained with two different softwares, using different standardization methods, for the measurement of GSM on ultrasound images of carotid human plaques. GSM was measured with Adobe Photoshop(®) and with Artery Measurement System (AMS) on duplex ultrasound images of 100 consecutive medium- to large-sized carotid plaques of the Beta-blocker Cholesterol-lowering Asymptomatic Plaque Study (BCAPS). The mean values of GSM were 35·2 ± 19·3 and 55·8 ± 22·5 for Adobe Photoshop(®) and AMS, respectively. Mean difference was 20·45 (95% CI: 19·17-21·73). Although the absolute values of GSM differed, the agreement between the two measurements was good, correlation coefficient 0·95. A chi-square test revealed a kappa value of 0·68 when studying quartiles of GSM. The intra-observer variability was 1·9% for AMS and 2·5% for Adobe Photoshop. The difference between softwares and standardization methods must be taken into consideration when comparing studies. To avoid these problems, researcher should come to a consensus regarding software and standardization method for GSM measurement on ultrasound images of plaque in the arteries. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  11. Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques.

    Directory of Open Access Journals (Sweden)

    Nazanin Hakimzadeh

    Full Text Available Molecular imaging of matrix metalloproteinases (MMPs may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9 with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT imaging that effectively targets atherosclerotic lesions in mice.

  12. Utility of magnetic resonance imaging-based finite element analysis for the biomechanical stress analysis of hemorrhagic and non-hemorrhagic carotid plaques

    International Nuclear Information System (INIS)

    Sadat, U.; Teng, Z.; Young, V.E.; Li, Z.Y.; Gillard, J.H.

    2011-01-01

    Biomechanical stress analysis has been used for plaque vulnerability assessment. The presence of plaque hemorrhage (PH) is a feature of plaque vulnerability and is associated with thromboembolic ischemic events. The purpose of the present study was to use finite element analysis (FEA) to compare the stress profiles of hemorrhagic and non-hemorrhagic profiles. Forty-five consecutive patients who had suffered a cerebrovascular ischemic event with an underlying carotid artery disease underwent high-resolution magnetic resonance imaging (MRI) of their symptomatic carotid artery in a 1.5-T MRI system. Axial images were manually segmented for various plaque components and used for FEA. Maximum critical stress (M-Cstress SL ) for each slice was determined. Within a plaque, the maximum M-Cstress SL for each slice of a plaque was selected to represent the maximum critical stress of that plaque (M-Cstress PL ) and used to compare hemorrhagic and non-hemorrhagic plaques. A total of 62% of plaques had hemorrhage. It was observed that plaques with hemorrhage had significantly higher stress (M-Cstress PL ) than plaques without PH (median [interquartile range]: 315kPa [247-434] vs. 200kPa [171-282], P=0.003). Hemorrhagic plaques have higher biomechanical stresses than non-hemorrhagic plaques. MRI-based FEA seems to have the potential to assess plaque vulnerability. (author)

  13. 2-D Versus 3-D Cross-Correlation-Based Radial and Circumferential Strain Estimation Using Multiplane 2-D Ultrafast Ultrasound in a 3-D Atherosclerotic Carotid Artery Model

    NARCIS (Netherlands)

    Fekkes, S.; Swillens, A.E.; Hansen, H.H.G.; Saris, A.E.C.M.; Nillesen, M.M.; Iannaccone, F.; Segers, P.; Korte, C.L. de

    2016-01-01

    Three-dimensional (3-D) strain estimation might improve the detection and localization of high strain regions in the carotid artery (CA) for identification of vulnerable plaques. This paper compares 2-D versus 3-D displacement estimation in terms of radial and circumferential strain using simulated

  14. Serial intravascular ultrasound assessment of changes in coronary atherosclerotic plaque dimensions and composition: an update

    DEFF Research Database (Denmark)

    Hartmann, Marc; Huisman, Jennifer; Böse, Dirk

    2011-01-01

    This manuscript reviews the use of serial intravascular ultrasound (IVUS) examination of coronary atherosclerosis in recent observational studies and randomized trials that revealed the effects of cholesterol-lowering and lipid-modifying therapies and offered novel insight into plaque progression....... Finally, we report on the evaluation of true vessel remodelling in recent serial IVUS trials and discuss the future perspective of serial invasive imaging of coronary atherosclerosis....

  15. Optical measurement of arterial mechanical properties: from atherosclerotic plaque initiation to rupture.

    Science.gov (United States)

    Nadkarni, Seemantini K

    2013-12-01

    During the pathogenesis of coronary atherosclerosis, from lesion initiation to rupture, arterial mechanical properties are altered by a number of cellular, molecular, and hemodynamic processes. There is growing recognition that mechanical factors may actively drive vascular cell signaling and regulate atherosclerosis disease progression. In advanced plaques, the mechanical properties of the atheroma influence stress distributions in the fibrous cap and mediate plaque rupture resulting in acute coronary events. This review paper explores current optical technologies that provide information on the mechanical properties of arterial tissue to advance our understanding of the mechanical factors involved in atherosclerosis development leading to plaque rupture. The optical approaches discussed include optical microrheology and traction force microscopy that probe the mechanical behavior of single cell and extracellular matrix components, and intravascular imaging modalities including laser speckle rheology, optical coherence elastography, and polarization-sensitive optical coherence tomography to measure the mechanical properties of advanced coronary lesions. Given the wealth of information that these techniques can provide, optical imaging modalities are poised to play an increasingly significant role in elucidating the mechanical aspects of coronary atherosclerosis in the future.

  16. 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)

  17. Magnetic Resonance Imaging Plaque Hemorrhage for Risk Stratification in Carotid Artery Disease With Moderate Risk Under Current Medical Therapy.

    Science.gov (United States)

    Hosseini, Akram A; Simpson, Richard J; Altaf, Nishath; Bath, Philip M; MacSweeney, Shane T; Auer, Dorothee P

    2017-03-01

    Magnetic resonance imaging (MRI)-defined carotid plaque hemorrhage (MRIPH) can predict recurrent cerebrovascular ischemic events in severe symptomatic carotid stenosis. It is less clear whether MRIPH can improve risk stratification despite optimized medical secondary prevention in those with moderate risk. One-hundred fifty-one symptomatic patients with 30% to 99% carotid artery stenosis (median age: 77, 60.5% men) clinically deemed to not benefit from endarterectomy were prospectively recruited to undergo MRI and clinical follow-up (mean, 22 months). The clinical carotid artery risk score could be evaluated in 88 patients. MRIPH+ve was defined as plaque intensity >150% that of adjacent muscle. Survival analyses were performed with recurrent infarction (stroke or diffusion-positive cerebral ischemia) as the main end point. Fifty-five participants showed MRIPH+ve; 47 had low, 36 intermediate, and 5 high carotid artery risk scores. Cox regression showed MRIPH as a strong predictor of future infarction (hazard ratio, 5.2; 95% confidence interval, 1.64-16.34; P =0.005, corrected for degree of stenosis), also in the subgroup with 50% to 69% stenosis (hazard ratio, 4.1; 95% confidence interval, 1-16.8; P =0.049). The absolute risk of future infarction was 31.7% at 3 years in MRIPH+ve versus 1.8% in patients without ( P medication with clinically uncertain benefit from recanalization, that is, those with moderate degree stenosis and intermediate carotid artery risk scores, MRIPH offers additional risk stratification. © 2017 American Heart Association, Inc.

  18. 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.

  19. Coincidence of calcified carotid atheromatous plaque, osteoporosis, and periodontal bone loss in dental panoramic radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Ramesh, Aruna; Ganguly, Rumpa [Dept. of Diagnosis and Health Promotion, Division of Oral and Maxillofacial Radiology, Tufts University School of Dental Medicine, Boston (United States); Soroushian, Sheila [Dept. of Orthodontics, Howard University College of Dentistry, Washington, DC(United States)

    2013-12-15

    This study was performed to assess the correlation of calcified carotid atheromatous plaque (CCAP), the mandibular cortical index, and periodontal bone loss in panoramic radiographs. One hundred eighty-five panoramic radiographs with CCAP and 234 without this finding were evaluated by 3 observers for the presence of osseous changes related to osteoporosis and periodontal bone loss. Chi-squared and Mann-Whitney U tests were used to compare the two groups for an association of CCAP with the mandibular cortical index and periodontal bone loss, respectively. There was a statistically significant coincidence of CCAP and osseous changes related to osteopenia/osteoporosis, with a p-value <0.001. There was no statistically significant coincidence of CCAP and periodontal bone loss. When comparing the 2 groups, 'With CCAP' and 'Without CCAP', there was a statistically significant association with the mean body mass index (BMI), number of remaining teeth, positive history of diabetes mellitus, and vascular accidents. There was no statistically significant association with gender or a history of smoking. This study identified a possible concurrence of CCAP and mandibular cortical changes secondary to osteopenia/osteoporosis in panoramic radiographs. This could demonstrate the important role of dental professionals in screening for these systemic conditions, leading to timely and appropriate referrals resulting in early interventions and thus improving overall health.

  20. Coincidence of calcified carotid atheromatous plaque, osteoporosis, and periodontal bone loss in dental panoramic radiographs

    International Nuclear Information System (INIS)

    Ramesh, Aruna; Ganguly, Rumpa; Soroushian, Sheila

    2013-01-01

    This study was performed to assess the correlation of calcified carotid atheromatous plaque (CCAP), the mandibular cortical index, and periodontal bone loss in panoramic radiographs. One hundred eighty-five panoramic radiographs with CCAP and 234 without this finding were evaluated by 3 observers for the presence of osseous changes related to osteoporosis and periodontal bone loss. Chi-squared and Mann-Whitney U tests were used to compare the two groups for an association of CCAP with the mandibular cortical index and periodontal bone loss, respectively. There was a statistically significant coincidence of CCAP and osseous changes related to osteopenia/osteoporosis, with a p-value <0.001. There was no statistically significant coincidence of CCAP and periodontal bone loss. When comparing the 2 groups, 'With CCAP' and 'Without CCAP', there was a statistically significant association with the mean body mass index (BMI), number of remaining teeth, positive history of diabetes mellitus, and vascular accidents. There was no statistically significant association with gender or a history of smoking. This study identified a possible concurrence of CCAP and mandibular cortical changes secondary to osteopenia/osteoporosis in panoramic radiographs. This could demonstrate the important role of dental professionals in screening for these systemic conditions, leading to timely and appropriate referrals resulting in early interventions and thus improving overall health.

  1. Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment

    Directory of Open Access Journals (Sweden)

    Manish Jain

    2016-09-01

    Full Text Available Photodynamic therapy (PDT, which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus this intra-arterial PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. Aim: We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®, efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Methods and Results: Visudyne® (100, 200 and 500 ng/ml was perfused for 5-30 minutes in atherosclerotic aorta isolated from ApoE-/- mice. The fluorescence Intensity (FI after 15 minutes of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8, 200 (FI-31.9 ± 1.9 or 500 ng/ml (FI-42.9 ± 1.2. Visudyne® (500 ng/ml uptake also increased with the administration time from 5 minutes (FI-9.8 ± 2.5 to 10 minutes (FI-23.3 ± 3.0 and 15 minutes (FI-42.9 ± 3.4 before reaching saturation at 30 minutes (FI-39.3 ± 2.4 contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm2, irradiance-334 mW/cm2 applied immediately after Visudyne® perfusion (500 ng/ml for 15 minutes using a cylindrical light diffuser coupled to a diode laser (690 nm, led to an increase of ROS (Dihydroethidium (FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9 and apoptotic cells (TUNEL (2.5 ± 1.6 %, 41.3 ± 15.3 %, 58.9 ± 6 %, mainly plaque macrophages (immunostaining (0.3 ± 0.2 %, 37.6 ± 6.4 %, 45.3 ± 5.4 % at light doses of 0, 100 or 200 J/cm2 respectively. Limited apoptosis was observed in the medial wall (0.5 ± 0.2 %, 8.5 ± 4.7 %, 15.3 ± 12.7 %. Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram. Conclusion: We demonstrated that sufficient accumulation of

  2. Intra-Arterial Drug and Light Delivery for Photodynamic Therapy Using Visudyne®: Implication for Atherosclerotic Plaque Treatment.

    Science.gov (United States)

    Jain, Manish; Zellweger, Matthieu; Frobert, Aurélien; Valentin, Jérémy; van den Bergh, Hubert; Wagnières, Georges; Cook, Stéphane; Giraud, Marie-Noelle

    2016-01-01

    Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus, this "intra-arterial" PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®), efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Visudyne® (100, 200, and 500 ng/ml) was perfused for 5-30 min in atherosclerotic aorta isolated from ApoE(-/-) mice. The fluorescence Intensity (FI) after 15 min of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8), 200 (FI-31.9 ± 1.9) or 500 ng/ml (FI-42.9 ± 1.2). Visudyne® (500 ng/ml) uptake also increased with the administration time from 5 min (FI-9.8 ± 2.5) to 10 min (FI-23.3 ± 3.0) and 15 min (FI-42.9 ± 3.4) before reaching saturation at 30 min (FI-39.3 ± 2.4) contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm(2), irradiance-334 mW/cm(2)) was applied immediately after Visudyne® perfusion (500 ng/ml for 15 min) using a cylindrical light diffuser coupled to a diode laser (690 nm). PDT led to an increase of ROS (Dihydroethidium; FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9) and apoptotic cells (TUNEL; 2.5 ± 1.6, 41.3 ± 15.3, 58.9 ± 6%), mainly plaque macrophages (immunostaining; 0.3 ± 0.2, 37.6 ± 6.4, 45.3 ± 5.4%) respectively without laser irradiation, or at 100 and 200 J/cm(2). Limited apoptosis was observed in the medial wall (0.5 ± 0.2, 8.5 ± 4.7, 15.3 ± 12.7%). Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram). We demonstrated that sufficient accumulation of Visudyne® within plaque could be achieved in short

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    Oxidation is believed to play a role in atherosclerosis. Oxidized lipids, sterols and proteins have been detected in early, intermediate and advanced human lesions at elevated levels. The spectrum of oxidized side-chain products detected on proteins from homogenates of advanced human lesions has...... been interpreted in terms of the occurrence of two oxidative mechanisms, one involving oxygen-derived radicals catalysed by trace transition metal ions, and a second involving chlorinating species (HOCl or Cl2), generated by the haem enzyme myeloperoxidase (MPO). As MPO is released extracellularly...... for 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...

  4. Non-Lethal Sonodynamic Therapy Inhibits Atherosclerotic Plaque Progression in ApoE-/- Mice and Attenuates ox-LDL-mediated Macrophage Impairment by Inducing Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2017-05-01

    Full Text Available Background: Previous studies from our group showed that low-intensity sonodynamic therapy (SDT has protective effects on atherosclerosis (AS. However, because the intensity of ultrasound passing through tissue is attenuated, the consequences of very low-intensity SDT, referred to as non-lethal SDT (NL-SDT, on atherosclerotic plaques are unclear. The aim of this study was to determine whether NL-SDT affects atherosclerotic plaques and to elucidate the possible underlying mechanisms. Methods: An AS model was established using ApoE-/- mice fed a western diet. En face Oil Red O staining was used to measure atherosclerotic plaque size. Hematoxylin and eosin staining and immunohistochemical staining were used to observe plaque morphology and assess the location of macrophages and heme oxygenase 1 (HO-1. HO-1 mRNA and protein levels in AS plaques were evaluated by real-time PCR and western blotting. Human THP-1 cells and mouse peritoneal macrophages were used in this study. Western blotting was used to investigate the expression of cellular proteins after NL-SDT. Macrophage apoptosis was evaluated by TUNEL assays and flow cytometry with Annexin V/PI double staining. Intracellular reactive oxygen species (ROS and mitochondrial membrane potential (MMP were measured with 2′-7′-dichlorofluorescein diacetate (DCFH-DA and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl benzimidazolyl carbocyanine iodide (JC-1 staining, respectively. Results: NL-SDT significantly inhibited AS progression and reduced the necrotic core area. NL-SDT induced HO-1 expression in lesional macrophages and in cultured macrophages. NL-SDT activated the protein kinase B (AKT and extracellular signal-related protein kinase (ERK pathways and the transcription factor NF-E2-related factor 2 (Nrf2.NL-SDT significantly reduced oxidized LDL (ox-LDL-induced macrophage MMP collapse, ROS production and cell apoptosis. Zinc protoporphyrin (ZnPP, a HO-1-specific inhibitor, reversed the

  5. 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

    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 disea......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 diseased human arteries but have often used methods that release metal ions from proteins. METHODS AND RESULTS: In this study, we have used the minimally invasive technique of electron paramagnetic resonance (EPR) spectroscopy and inductively coupled plasma mass spectroscopy (ICPMS) to quantify iron...... and 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...

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

    Directory of Open Access Journals (Sweden)

    Ivanović Miloš

    2013-01-01

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

  7. Dual-energy CT head bone and hard plaque removal for quantification of calcified carotid stenosis: utility and comparison with digital subtraction angiography

    International Nuclear Information System (INIS)

    Uotani, Kensuke; Watanabe, Yoshiyuki; Higashi, Masahiro; Nakazawa, Tetsuro; Kono, Atsushi K.; Hori, Yoshiro; Fukuda, Tetsuya; Kanzaki, Suzu; Yamada, Naoaki; Naito, Hiroaki; Itoh, Toshihide; Sugimura, Kazuro

    2009-01-01

    We evaluated quantification of calcified carotid stenosis by dual-energy (DE) CTA and dual-energy head bone and hard plaque removal (DE hard plaque removal) and compared the results to those of digital subtraction angiography (DSA). Eighteen vessels (13 patients) with densely calcified carotid stenosis were examined by dual-source CT in the dual-energy mode (tube voltages 140 kV and 80 kV). Head bone and hard plaques were removed from the dual-energy images by using commercial software. Carotid stenosis was quantified according to NASCET criteria on MIP images and DSA images at the same plane. Correlation between DE CTA and DSA was determined by cross tabulation. Accuracies for stenosis detection and grading were calculated. Stenosis could be evaluated in all vessels by DE CTA after applying DE hard plaque removal. In contrast, conventional CTA failed to show stenosis in 13 out of 18 vessels due to overlapping hard plaque. Good correlation between DE plaque removal images and DSA images was observed (r 2 =0.9504) for stenosis grading. Sensitivity and specificity to detect hemodynamically relevant (>70%) stenosis was 100% and 92%, respectively. Dual-energy head bone and hard plaque removal is a promising tool for the evaluation of densely calcified carotid stenosis. (orig.)

  8. Intermittent cold stress enhances features of atherosclerotic plaque instability in apolipoprotein E‑deficient mice.

    Science.gov (United States)

    Zheng, Xi; Wang, Qiang; Zhang, Yan; Yang, Dachun; Li, De; Tang, Bing; Li, Xiuchuan; Yang, Yongjian; Ma, Shuangtao

    2014-10-01

    The cold weather is associated with an increased occurrence of acute coronary events. However, the mechanisms underlying cold‑induced myocardial infarctions have not yet been fully elucidated. In the present study, 20 male, eight week‑old, apolipoprotein E (ApoE)‑deficient mice were subjected to either control conditions or intermittent cold exposure for eight weeks. Mice in the cold group were placed in a cold room at 4˚C for 4 h per day, while the mice in the control group were kept in a room at 24˚C. Cold‑exposed mice did not significantly differ from control mice in body weight, fasting glucose concentration and plasma lipid levels, including triglyceride, total cholesterol, low‑density lipoprotein and high‑density lipoprotein. The hematoxylin and eosin‑stained sections of the aortic root demonstrated increased plaque size in the cold group compared with the control group (Pinstability. Additionally, the protein expression of matrix metalloproteinase (MMP)‑2, MMP‑9 and MMP‑14 were significantly increased (Pinstability in ApoE‑deficient mice by altering the balance of MMPs and TIMPs. These findings may provide mechanistic insights into sudden cardiac death in cold environments.

  9. Current smoking is associated with extracranial carotid atherosclerotic stenosis but not with intracranial large artery disease.

    Science.gov (United States)

    Ji, Ruijun; Pan, Yuesong; Yan, Hongyi; Zhang, Runhua; Liu, Gaifen; Wang, Penglian; Wang, Yilong; Li, Hao; Zhao, Xingquan; Wang, Yongjun

    2017-06-26

    Accumulating evidence has shown that cigarette smoking is an important risk factor for ischemic stroke. However, it is not clear about the potential mechanisms through which cigarette smoking affects stroke risk. In the study, we aimed to investigate the relationship between cigarette smoking and the occurrence of extracranial (ECAS) and intracranial atherosclerotic stenosis (ICAS). We analyzed patients enrolled in the Chinese intracranial atherosclerosis (CICAS), which was a prospective, multicenter, hospital-based cohort study. Smoking status was classified into never, former and current smoking. For those patients with current smoking, data on time duration (year) and extent (the number of cigarette smoked per day) was recorded and pack year of smoking was calculated. ICAS was evaluated with 3-dimentional time-of-flight MRA and ECAS was evaluated with cervical ultrasonography or contrast-enhanced MRA. Multivariable Logistic regression was performed to identify the association between smoking status and the occurrence of ECAS and ICAS. A total of 2656 patients (92.7%) of acute ischemic stroke and 208 (7.3%) of transient ischemic attack were analyzed. The mean age was 61.9 ± 11.2 and 67.8% were male. There were 141 (4.9%) patients had only ECAS, 1074 (37.5%) had only ICAS, and 261 (9.1%) had both ECAS and ICAS. Current smoking was significantly associated with the occurrence of ECAS (adjusted OR = 1.47, 95% CI = 1.09-1.99, P smoking increment, the risk of ECAS increased by 1.1% (adjusted OR = 1.011; 95% CI = 1.003-1.019; P = 0.005); with one cigarette smoked per day increment, the risk of ECAS increased by 1.0% (adjusted OR = 1.010; 95% CI = 1.001-1.020; P = 0.03); and with one pack year of smoking increment, the risk of ECAS increased by 0.7% (adjusted OR = 1.007; 95% CI = 1.002-1.012; P smoking status and the occurrence of ICAS. A dose-response relationship was identified between cigarette smoking and the occurrence of ECAS, but not ICAS

  10. Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by Regulating NF-κB Dependent Matrix Metalloproteinase-9 Expression via LPA2 in Macrophages

    Directory of Open Access Journals (Sweden)

    Xi Chen

    2017-04-01

    Full Text Available Lysophosphatidic acid (LPA, one of the simplest phospholipid signaling molecules, participates in formation and disruption of atherosclerotic plaque. Matrix metalloproteinases (MMPs contribute to atherosclerotic plaque rupture by involving in extracellular matrix (ECM degradation and then thinning fibrous cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated with coronary plaque instability, but the relationship between LPA and MMP-9 remains unclear. The present work therefore aimed at elucidating association between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in macrophages. We found that plasma LPA and MMP-9 levels were correlated positively (r = 0.31, P < 0.05 and both elevated significantly in patients with acute myocardial infarct (AMI. Consistent with peripheral blood levels, histochemical staining indicated that autotaxin (ATX, LPA-producing ectoenzyme, and MMP-9 were expressed frequently in the necrotic core and fibrous cap of human unstable plaques, which might increase the instability of plaque. Experiments in vitro were done with THP-1-derived macrophages and showed that LPA enhanced the expression, secretion and activity of MMP-9 in a time- and dose-dependent manner. Induction of LPA on pro-MMP-9 and active-MMP-9 was confirmed in human peripheral blood monocyte-derived macrophages. PDTC, NF-κB inhibitor, but not inhibitor of AP-1 and PPARγ, effectively prevented LPA-induced MMP-9 expression and NF-κB p65 siRNA decreased MMP-9 transcription, confirming that LPA might induce MMP-9 elevation by activating NF-κB pathway. In addition, knockdown of LPA2 attenuated LPA-induced MMP-9 expression and nucleus p65 levels. These findings revealed that LPA upregulated the expression of MMP-9 through activating NF-κB pathway in the LPA2 dependent manner, hence blocking LPA receptors signaling may provide therapeutic strategy to target plaque destabilization.

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

    International Nuclear Information System (INIS)

    Kuge, Yuji; Takai, Nozomi; Ogawa, Yuki; Temma, Takashi; Nishigori, Kantaro; Ishino, Seigo; Kamihashi, Junko; Saji, Hideo; Zhao, Yan; Kiyono, Yasushi; Shiomi, Masashi

    2010-01-01

    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 99m Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG 3 and negative control IgG 3 were radiolabelled with 99m Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield 99m Tc-MT1-MMP mAb and 99m Tc-IgG 3 , 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. 99m Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional 99m Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p 99m Tc-IgG 3 accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest 99m Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 ± 1.9, %ID x BW/mm 2 x 10 2 ), 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, 99m Tc-IgG 3 accumulation was almost independent of the histological grade of lesions. Higher 99m Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with 99m Tc-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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Kuge, Yuji [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Takai, Nozomi; Ogawa, Yuki; Temma, Takashi; Nishigori, Kantaro; Ishino, Seigo; Kamihashi, Junko; Saji, Hideo [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Zhao, Yan [Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Kiyono, Yasushi [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); University of Fukui, Biomedical Imaging Research Center, Fukui (Japan); Shiomi, Masashi [Kobe University Graduate School of Medicine, Institute for Experimental Animals, Kobe (Japan)

    2010-11-15

    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 {sup 99m}Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG{sub 3} and negative control IgG{sub 3} were radiolabelled with {sup 99m}Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield {sup 99m}Tc-MT1-MMP mAb and {sup 99m}Tc-IgG{sub 3}, 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. {sup 99m}Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional {sup 99m}Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p < 0.0001), while {sup 99m}Tc-IgG{sub 3} accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest {sup 99m}Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 {+-} 1.9, %ID x BW/mm{sup 2} x 10{sup 2}), 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, {sup 99m}Tc-IgG{sub 3} accumulation was almost independent of the histological grade of lesions. Higher {sup 99m}Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with {sup 99m}Tc-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.)

  13. Association of egg consumption and calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study.

    Science.gov (United States)

    Robbins, Jeremy M; Petrone, Andrew B; Ellison, R Curtis; Hunt, Steven C; Carr, J Jeffrey; Heiss, Gerardo; Arnett, Donna K; Gaziano, J Michael; Djoussé, Luc

    2014-06-01

    Eggs are a ubiquitous and important source of dietary cholesterol and nutrients, yet their relationship to coronary heart disease (CHD) remains unclear. While some data have suggested a positive association between egg consumption and CHD, especially among diabetic subjects, limited data exist on the influence of egg consumption on subclinical disease. Thus, we sought to examine whether egg consumption is associated with calcified atherosclerotic plaques in the coronary arteries. In a cross-sectional design, we studied 1848 participants of the NHLBI Family Heart Study without known CHD. Egg consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age was 56.5 years and 41% were male. Median consumption of eggs was 1/week. There was no association between frequency of egg consumption and prevalent CAC. Odds ratios (95% CI) for CAC were 1.0 (reference), 0.95 (0.66-1.38), 0.94 (0.63-1.40), and 0.90 (0.57-1.42) for egg consumption of almost never, 1-3 times per month, once per week, and 2+ times per week, respectively (p for trend 0.66), adjusting for age, sex, BMI, smoking, alcohol, physical activity, income, field center, total calories, and bacon. Additional control for hypertension and diabetes mellitus, or restricting the analysis to subjects with diabetes mellitus or fasting glucose >126 mg/dL did not alter the findings. These data do not provide evidence for an association between egg consumption and prevalent CAC in adult men and women.

  14. Lower prevalence of carotid plaque hemorrhage in women, and its mediator effect on sex differences in recurrent cerebrovascular events.

    Directory of Open Access Journals (Sweden)

    Neghal Kandiyil

    Full Text Available Women are at lower risk of stroke, and appear to benefit less from carotid endarterectomy (CEA than men. We hypothesised that this is due to more benign carotid disease in women mediating a lower risk of recurrent cerebrovascular events. To test this, we investigated sex differences in the prevalence of MRI detectable plaque hemorrhage (MRI PH as an index of plaque instability, and secondly whether MRI PH mediates sex differences in the rate of cerebrovascular recurrence.Prevalence of PH between sexes was analysed in a single centre pooled cohort of 176 patients with recently symptomatic, significant carotid stenosis (106 severe [≥70%], 70 moderate [50-69%] who underwent prospective carotid MRI scanning for identification of MRI PH. Further, a meta-analysis of published evidence was undertaken. Recurrent events were noted during clinical follow up for survival analysis.Women with symptomatic carotid stenosis (50%≥ were less likely to have plaque hemorrhage (PH than men (46% vs. 70% with an adjusted OR of 0.23 [95% CI 0.10-0.50, P<0.0001] controlling for other known vascular risk factors. This negative association was only significant for the severe stenosis subgroup (adjusted OR 0.18, 95% CI 0.067-0.50 not the moderate degree stenosis. Female sex in this subgroup also predicted a longer time to recurrent cerebral ischemic events (HR 0.38 95% CI 0.15-0.98, P = 0.045. Further addition of MRI PH or smoking abolished the sex effects with only MRI PH exerting a direct effect. Meta-analysis confirmed a protective effect of female sex on development of PH: unadjusted OR for presence of PH = 0.54 (95% CI 0.45-0.67, p<0.00001.MRI PH is significantly less prevalent in women. Women with MRI PH and severe stenosis have a similar risk as men for recurrent cerebrovascular events. MRI PH thus allows overcoming the sex bias in selection for CEA.

  15. Fractalkine is expressed in early and advanced atherosclerotic lesions and supports monocyte recruitment via CX3CR1.

    Directory of Open Access Journals (Sweden)

    Moritz Stolla

    Full Text Available Fractalkine (CX3CL1, FKN is expressed in the inflamed vascular wall and absence of FKN reduces atherogenesis. Whether FKN is expressed throughout all stages of atherosclerotic disease and whether it directly contributes to monocyte recruitment to atherosclerotic lesions is not known. We collected human atherosclerotic plaque material and blood samples from patients with carotid artery disease undergoing endarterectomy. Plaques were analyzed by immunohistochemistry and qPCR. We found that FKN is expressed at all stages of atherosclerotic lesion formation, and that the number of FKN-expressing cells positively correlates with the number of CX3CR1-positive cells in human carotid artery plaques. In the circulation, soluble FKN levels are significantly elevated in the presence of high-grade (sub-occlusive stenosis. To determine the role of the FKN-CX3CR1 axis for monocyte adhesion in vivo we then performed intravital videofluorescence microscopy of the carotid artery in ApoE(-/- mice. Notably, FKN-CX3CR1 interactions are critical for recruitment of circulating monocytes to the injured atherosclerotic vascular wall. Thus, this chemokine dyad could represent an attractive target for anti-atherosclerotic strategies.

  16. Non-invasive carotid artery imaging to identify the vulnerable plaque : Current status and future goals

    NARCIS (Netherlands)

    Huibers, A.; De Borst, G. J.|info:eu-repo/dai/nl/237108151; Wan, S.; Kennedy, F.; Giannopoulos, A.; Moll, F. L.|info:eu-repo/dai/nl/070246882; Richards, T.

    2015-01-01

    Background The current clinical practise to determine if a patient should undergo carotid intervention to prevent stroke is to determine the clinical features combined with degree of carotid stenosis. However, this does not accurately determine the individual patient's risk for future stroke. A thin

  17. SMARTool: A tool for clinical decision support for the management of patients with coronary artery disease based on modeling of atherosclerotic plaque process.

    Science.gov (United States)

    Sakellarios, Antonis I; Rigas, George; Kigka, Vassiliki; Siogkas, Panagiotis; Tsompou, Panagiota; Karanasiou, Georgia; Exarchos, Themis; Andrikos, Ioannis; Tachos, Nikolaos; Pelosi, Gualtriero; Parodi, Oberdan; Fotiaids, Dimitrios I

    2017-07-01

    SMARTool aims to the development of a clinical decision support system (CDSS) for the management and stratification of patients with coronary artery disease (CAD). This will be achieved by performing computational modeling of the main processes of atherosclerotic plaque growth. More specifically, computed tomography coronary angiography (CTCA) is acquired and 3-dimensional (3D) reconstruction is performed for the arterial trees. Then, blood flow and plaque growth modeling is employed simulating the major processes of atherosclerosis, such as the estimation of endothelial shear stress (ESS), the lipids transportation, low density lipoprotein (LDL) oxidation, macrophages migration and plaque development. The plaque growth model integrates information from genetic and biological data of the patients. The SMARTool system enables also the calculation of the virtual functional assessment index (vFAI), an index equivalent to the invasively measured fractional flow reserve (FFR), to provide decision support for patients with stenosed arteries. Finally, it integrates modeling of stent deployment. In this work preliminary results are presented. More specifically, the reconstruction methodology has mean value of Dice Coefficient and Hausdorff Distance is 0.749 and 1.746, respectively, while low ESS and high LDL concentration can predict plaque progression.

  18. Association between body mass index and presence of carotid plaque among low-income adults aged 45 years and older: a population-based cross-sectional study in rural China.

    Science.gov (United States)

    Lou, Yongzhong; Li, Bin; Su, Lan; Mu, Zhenhong; Sun, Minghao; Gu, Hongfei; Ni, Jingxian; Wu, Yanan; Tu, Jun; Wang, Jinghua; Ning, Xianjia

    2017-10-06

    Carotid plaque is a good surrogate endpoint for assessing arterial atherosclerosis, and atherosclerosis is a reliable predictor of cardiovascular diseases. However, the effect of body mass index on carotid plaque is unknown. Therefore, we aimed to explore the association between body mass index and carotid plaque in a low-income Chinese population. Residents aged ≥45 years and free of stroke and cardiovascular diseases were enrolled and divided into four groups based on body mass index. B-mode ultrasonography was performed to measure carotid plaque. The mean age of participants was 59.92 years overall. Significant correlations were observed between the presence of carotid plaque and male sex, older age, systolic blood pressure, fasting plasma glucose, and low-density lipoprotein cholesterol among the different BMI subgroups. Male sex increased the risk of carotid plaque in the overweight and obese groups. Older age and high level of low-density lipoprotein cholesterol were the independent risk factor for carotid plaque in four groups. Increased systolic blood pressure was an independent risk factor in the normal-weight, overweight, and obese groups; however, fasting plasma glucose was only significant in the normal-weight group. Thus, controlling the levels of low-density lipoprotein cholesterol, systolic blood pressure, and fasting plasma glucose is required to reduce carotid plaque risk.

  19. 3D black blood MR angiography of the carotid arteries. A simple sequence for plaque hemorrhage and stenosis evaluation.

    Science.gov (United States)

    Sigovan, Monica; Bidet, Clément; Bros, Sébastien; Boussel, Loic; Mechtouff, Laura; Robson, Philip M; Fayad, Zahi A; Millon, Antoine; Douek, Philippe

    2017-10-01

    To evaluate the diagnostic performance of a new three-dimensional T1-weighted turbo-spin-echo sequence (3D T1-w TSE) compared to 3D contrast-enhanced angiography (CE-MRA) for stenosis measurement and compared to 2D T1-w TSE for intra-plaque hemorrhage (IPH) detection. Eighty three patients underwent carotid MRI, using a new elliptic-centric phase encoding T1-weighted 3D TSE sequence in addition to the clinical protocol. Two observers evaluated image quality, presence of flow artifacts, and presence of intra-plaque hemorrhage, and computed the NASCET degree of stenosis for CE-MRA and for the new sequence. Inter-observer agreement and correlation between 3D TSE and CE-MRA for NASCET stenosis was estimated using Cohen's kappa, and correlation using linear regression and Bland-Altman plots. Histology was performed on endarterectomy samples for 18 patients. Sensitivity and specificity of 2D and 3D TSE for IPH diagnosis were computed. 3D TSE showed better image quality than 2D TSE (pw TSE allows both reliable measures of carotid stenosis, with a slight overestimation compared to CE-MRA (5%), and improved IPH identification, compared to 2D TSE. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Endothelial dysfunction, carotid artery plaque burden, and conventional exercise-induced myocardial ischemia as predictors of coronary artery disease prognosis

    Directory of Open Access Journals (Sweden)

    Ishihara Masayuki

    2008-12-01

    Full Text Available Abstract Background While both flow-mediated vasodilation (FMD in the brachial artery (BA, which measures endothelium-dependent vasodilatation, and intima-media thickness (IMT in the carotid artery are correlated with the prognosis of coronary artery disease (CAD, it is not clear which modality is a better predictor of CAD. Furthermore, it has not been fully determined whether either of these modalities is superior to conventional ST-segment depression on exercise stress electrocardiogram (ECG as a predictor. Thus, the goal of the present study was to compare the predictive value of FMD, IMT, and stress ECG for CAD prognosis. Methods and Results A total of 103 consecutive patients (62 ± 9 years old, 79 men with clinically suspected CAD had FMD and nitroglycerin-induced dilation (NTG-D in the BA, carotid artery IMT measurement using high-resolution ultrasound, and exercise treadmill testing. The 73 CAD patients and 30 normal coronary patients were followed for 50 ± 15 months. Fifteen patients had coronary events during this period (1 cardiac death, 2 non-fatal myocardial infarctions, 3 acute heart failures, and 9 unstable anginas. On Kaplan-Meier analysis, only FMD and stress ECG were significant predictors for cardiac events. Conclusion Brachial endothelial function as reflected by FMD and conventional exercise stress testing has comparable prognostic value, whereas carotid artery plaque burden appears to be less powerful for predicting future cardiac events.

  1. Effect of ginkgo capsules combined with secondary preventive drugs on the endothelial injury and plaque properties of patients with hypertension complicated by carotid atherosclerosis

    Directory of Open Access Journals (Sweden)

    Wei Li

    2017-10-01

    Full Text Available Objective: To study the effect of ginkgo capsules combined with secondary preventive drugs on the endothelial injury and plaque properties of patients with hypertension complicated by carotid atherosclerosis. Methods: A total of 178 patients with hypertension complicated by carotid atherosclerosis who were treated in Chengyue Community Health Service Center of Xisaishan District Huangshi City Hubei Province between February 2015 and January 2017 were collected and randomly divided into two groups. Control group were treated with conventional secondary preventive drugs, and observation group were treated with ginkgo capsules combined with secondary preventive drugs. The differences in serum endothelial injury indexes and lipid metabolism indexes as well as carotid artery ultrasound parameters were compared between the two groups before and after treatment. Results: Before treatment, endothelial injury indexes and lipid metabolism indexes as well as carotid artery ultrasound parameters were not significantly different between two groups. After treatment, serum ET, AngⅡ, TC, LDL-C and LpA contents as well as carotid artery ultrasound parameters DS and AS levels of observation group were lower than those of control group while serum NO and HDL-C contents as well as carotid artery ultrasound parameter MLD level were higher than those of control group. Conclusion: Ginkgo capsule combined with secondary preventive drugs can effectively reduce the endothelial injury and stabilize the plaques in patients with hypertension complicated by carotid atherosclerosis.

  2. Plaque Tissue Morphology-Based Stroke Risk Stratification Using Carotid Ultrasound: A Polling-Based PCA Learning Paradigm.

    Science.gov (United States)

    Saba, Luca; Jain, Pankaj K; Suri, Harman S; Ikeda, Nobutaka; Araki, Tadashi; Singh, Bikesh K; Nicolaides, Andrew; Shafique, Shoaib; Gupta, Ajay; Laird, John R; Suri, Jasjit S

    2017-06-01

    Severe atherosclerosis disease in carotid arteries causes stenosis which in turn leads to stroke. Machine learning systems have been previously developed for plaque wall risk assessment using morphology-based characterization. The fundamental assumption in such systems is the extraction of the grayscale features of the plaque region. Even though these systems have the ability to perform risk stratification, they lack the ability to achieve higher performance due their inability to select and retain dominant features. This paper introduces a polling-based principal component analysis (PCA) strategy embedded in the machine learning framework to select and retain dominant features, resulting in superior performance. This leads to more stability and reliability. The automated system uses offline image data along with the ground truth labels to generate the parameters, which are then used to transform the online grayscale features to predict the risk of stroke. A set of sixteen grayscale plaque features is computed. Utilizing the cross-validation protocol (K = 10), and the PCA cutoff of 0.995, the machine learning system is able to achieve an accuracy of 98.55 and 98.83%corresponding to the carotidfar wall and near wall plaques, respectively. The corresponding reliability of the system was 94.56 and 95.63%, respectively. The automated system was validated against the manual risk assessment system and the precision of merit for same cross-validation settings and PCA cutoffs are 98.28 and 93.92%for the far and the near wall, respectively.PCA-embedded morphology-based plaque characterization shows a powerful strategy for risk assessment and can be adapted in clinical settings.

  3. In vivo inhibition of nuclear factor of activated T-cells leads to atherosclerotic plaque regression in IGF-II/LDLR-/-ApoB100/100 mice.

    Science.gov (United States)

    Blanco, Fabiana; Heinonen, Suvi E; Gurzeler, Erika; Berglund, Lisa M; Dutius Andersson, Anna-Maria; Kotova, Olga; Jönsson-Rylander, Ann-Cathrine; Ylä-Herttuala, Seppo; Gomez, Maria F

    2018-03-01

    Despite vast clinical experience linking diabetes and atherosclerosis, the molecular mechanisms leading to accelerated vascular damage are still unclear. Here, we investigated the effects of nuclear factor of activated T-cells inhibition on plaque burden in a novel mouse model of type 2 diabetes that better replicates human disease. IGF-II/LDLR -/- ApoB 100/100 mice were generated by crossbreeding low-density lipoprotein receptor-deficient mice that synthesize only apolipoprotein B100 (LDLR -/- ApoB 100/100 ) with transgenic mice overexpressing insulin-like growth factor-II in pancreatic β cells. Mice have mild hyperglycaemia and hyperinsulinaemia and develop complex atherosclerotic lesions. In vivo treatment with the nuclear factor of activated T-cells blocker A-285222 for 4 weeks reduced atherosclerotic plaque area and degree of stenosis in the brachiocephalic artery of IGF-II/LDLR -/- ApoB 100/100 mice, as assessed non-invasively using ultrasound biomicroscopy prior and after treatment, and histologically after termination. Treatment had no impact on plaque composition (i.e. muscle, collagen, macrophages). The reduced plaque area could not be explained by effects of A-285222 on plasma glucose, insulin or lipids. Inhibition of nuclear factor of activated T-cells was associated with increased expression of atheroprotective NOX4 and of the anti-oxidant enzyme catalase in aortic vascular smooth muscle cells. Targeting the nuclear factor of activated T-cells signalling pathway may be an attractive approach for the treatment of diabetic macrovascular complications.

  4. Inter-Scan Reproducibility of Carotid Plaque Volume Measurements by 3-D Ultrasound

    DEFF Research Database (Denmark)

    Sandholt, Benjamin V; Collet-Billon, Antoine; Entrekin, Robert

    2018-01-01

    (PPV) measure centered on MPT. Total plaque volume (TPV), PPV from a 10-mm segment and MPT were measured using dedicated semi-automated software on 38 plaques from 26 patients. Inter-scan reproducibility was assessed using the t-test, Bland-Altman plots and Pearson's correlation coefficient...

  5. When to image carotid plaque inflammation with FDG PET/CT

    DEFF Research Database (Denmark)

    Græbe, Martin; Borgwardt, Lise; Højgaard, Liselotte

    2010-01-01

    the contrast between the plaque and blood-pool FDG activity. However, for prospective studies the late acquisition is inconvenient for the patient and staff, and most retrospective studies of plaque uptake use data from early acquisition protocols. The objective was to evaluate changes in the quantification...

  6. Lack of association between ABO, PPAP2B, ADAMST7, PIK3CG, and EDNRA and carotid intima-media thickness, carotid plaques, and cardiovascular disease in patients with rheumatoid arthritis.

    Science.gov (United States)

    López-Mejías, Raquel; Genre, Fernanda; García-Bermúdez, Mercedes; Ubilla, Begoña; Castañeda, Santos; Llorca, Javier; González-Juanatey, Carlos; Corrales, Alfonso; Miranda-Filloy, José A; Pina, Trinitario; Gómez-Vaquero, Carmen; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Pascual-Salcedo, Dora; López-Longo, Francisco J; Carreira, Patricia; Blanco, Ricardo; Martín, Javier; González-Gay, Miguel A

    2014-01-01

    Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. Recent studies have identified the ABO rs579459, PPAP2B rs17114036, and ADAMTS7 rs3825807 polymorphisms as genetic variants associated with coronary artery disease and the PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms as the most significant signals related to the presence of carotid plaque in nonrheumatic Caucasian individuals. Accordingly, we evaluated the potential relationship between these 5 polymorphisms and subclinical atherosclerosis (assessed by carotid intima-media thickness (cIMT) and presence/absence of carotid plaques) and CV disease in RA. 2140 Spanish RA patients were genotyped for the 5 polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 620 of these patients by carotid ultrasonography technology. No statistically significant differences were found when each polymorphism was assessed according to cIMT values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV disease after adjusting for potential confounders. Our results do not confirm association between ABO rs579459, PPAP2B rs17114036, ADAMTS7 rs3825807, PIK3CG rs17398575, and EDNRA rs1878406 and subclinical atherosclerosis and CV disease in RA.

  7. Haploinsufficiency of E-selectin ligand-1 is Associated with Reduced Atherosclerotic Plaque Macrophage Content while Complete Deficiency Leads to Early Embryonic Lethality in Mice

    Science.gov (United States)

    Luo, Wei; Wang, Hui; Guo, Chiao; Wang, Jintao; Kwak, Jeffrey; Bahrou, Kristina L; Eitzman, Daniel T.

    2012-01-01

    E-selectin-1 (ESL-1), also known as golgi complex-localized glycoprotein-1 (GLG1), homocysteine-rich fibroblast growth factor receptor (CGR-1), and latent transforming growth factor-β complex protein 1 (LTCP-1), is a multifunctional protein with widespread tissue distribution. To determine the functional consequences of ESL-1 deficiency, mice were generated carrying an ESL-1 gene trap. After backcrossing to C57BL6/J for 6 generations, mice heterozygous for the gene trap (ESL-1+/-) were intercrossed to produce ESL-1-/- mice, however ESL-1-/- mice were not viable, even at embryonic day E10.5. To determine the effect of heterozygous ESL-1 deficiency on atherosclerosis, apolipoprotein E deficient (ApoE-/-), ESL-1+/- mice were generated and fed western diet. Compared to ApoE-/-, ESL-1++ mice, atherosclerotic lesions from ApoE-/-, ESL-1+/- contained more collagen and fewer macrophages, suggesting increased plaque stability. In conclusion, heterozygous deficiency of ESL-1 is associated with features of increased atherosclerotic plaque stability while complete deficiency of ESL-1 leads to embryonic lethality. PMID:22939356

  8. Integrated System for the Complete Segmentation of the Common Carotid Artery Bifurcation in Ultrasound Images

    OpenAIRE

    Loizou , Christos ,; Kasparis , Takis; Spyrou , Christina; Pantziaris , Marios

    2013-01-01

    Part 8: Third Workshop on Artificial Intelligence Applications in Biomedicine (AIAB 2013); International audience; The complete segmentation of the common carotid artery (CCA) bifurcation in ultrasound images is important for the evaluation of atherosclerosis disease and the quantification of the risk of stroke. This requires the extraction of the intima-media complex (IMC), the delineation of the lumen the atherosclerotic carotid plaque and measurement of the artery stenosis. The current res...

  9. Human antimicrobial peptide LL-37 is present in atherosclerotic plaques and induces death of vascular smooth muscle cells: a laboratory study

    Directory of Open Access Journals (Sweden)

    Sternby Nils H

    2006-12-01

    Full Text Available Abstract Background Death of smooth muscle cells in the atherosclerotic plaques makes the plaques more prone to rupture, which can initiate an acute ischemic event. The development of atherosclerosis includes the migration of immune cells e.g. monocytes/macrophages and T lymphocytes into the lesions. Immune cells can release antimicrobial peptides. One of these, human cathelicidin antimicrobial peptide hCAP-18, is cleaved by proteinase 3 generating a 4.5 kDa C-terminal fragment named LL-37, which has been shown to be cytotoxic. The aim of the study was to explore a potential role of LL-37 in the pathophysiology of atherosclerosis. Methods We investigated the presence of LL-37 in human atherosclerotic lesions obtained at autopsy using immunohistochemistry. The direct effects of LL-37 on cultured vascular smooth muscle cells and isolated neutrophil granulocytes were investigated with morphological, biochemical and flow cytometry analysis. Results The neointima of atherosclerotic plaques was found to contain LL-37-like immunoreactivity, mainly in macrophages. In cultured smooth muscle cells, LL-37 at 30 μg/ml caused cell shrinkage, membrane blebbing, nuclear condensation, DNA fragmentation and an increase in caspase-3 activity as studied by microscopy, ELISA and enzyme activity assay, respectively. Flow cytometry demonstrated that LL-37 in a subset of the cells caused a small but rapidly developing increase in membrane permeability to propidium iodide, followed by a gradual development of FITC-annexin V binding. Another cell population stained heavily with both propidium iodide and FITC-annexin V. Neutrophil granulocytes were resistant to these effects of LL-37. Conclusion This study shows that LL-37 is present in atherosclerotic lesions and that it induces death of vascular smooth muscle cells. In a subset of cells, the changes indicate the development of apoptosis triggered by an initial mild perturbation of plasma membrane integrity. The

  10. Characterization and morphology of atherosclerotic plaque of coronary arteries: utility of electron-beam tomography to detect non-calcified plaque: a comparison with conventional coronary angiography and intravascular ultrasound.

    Science.gov (United States)

    Funabashi, Nobusada; Misumi, Kazuo; Ohnishi, Hiroyuki; Asano, Miki; Komuro, Issei

    2007-01-31

    Electron-beam tomography (EBT) may provide useful information about characterization and morphology of atherosclerotic plaque of coronary arteries. Twenty-six subjects (20 male, 6 female) with suspected coronary heart disease had two routine (r) and one enhanced (e) EBT scans to detect non-calcified plaque (NCP) in the coronary arterial lumen, and were compared with conventional coronary angiograms (CAG) and intravascular ultrasound (IVUS). Three had the sites, which did not have high CT values suggesting calcification in rEBT, nor which was not enhanced by contrast material in eEBT. One had the site with positive CT values that were supposed to be the proliferation intima or organized thrombus and at the corresponding site mixed plaque was observed in the IVUS image. The other two had the site with negative CT values that were supposed to be fat tissue with significant stenosis in CAG. We also made the cross-sectional images of the vessel and the morphology of the NCP, which projected into the lumen, could be evaluated. We could detect the NCP, differentiate fat tissue from soft tissue and evaluate the morphology of the plaque in EBT.

  11. Negative MR contrast caused by USPIO uptake in lymph nodes may lead to false positive observations with in vivo visualization of murine atherosclerotic plaque.

    Science.gov (United States)

    te Boekhorst, Bernard C M; Bovens, Sandra M; Nederhoff, Marcel G J; van de Kolk, Kees W A; Cramer, Maarten J M; van Oosterhout, Matthijs F M; Ten Hove, Michiel; Doevendans, Pieter A; Pasterkamp, Gerard; van Echteld, Cees J A

    2010-05-01

    USPIOs are used clinically as contrast agent for magnetic resonance imaging (MRI) of lymph nodes, and in research settings for MRI of macrophages in atherosclerotic lesions. However, T2* weighted (T2*w) imaging can lead to "blooming" with overestimation of the area occupied by USPIOs. In this study, plaque uptake of USPIOs in atherosclerotic mice was investigated in the presence and absence of circulating monocytes. The influence of peri-aortic lymph node uptake on the interpretation of T2*w images of the aortic wall was studied. Atherosclerotic mice were fed an atherogenic diet and were randomized to total body irradiation or non-irradiation. After 2 days, T2*w MRI of the abdominal aorta was performed, followed by intravenous administration of 100mumol/kg USPIOs (t=0). At t=3 and 5 days MRI of the abdominal aorta was repeated. Animals were sacrificed and histological evidence for iron uptake by aortic wall and lymph nodes was compared with the degree of focal signal loss on in vivo MR images. Aortic walls in irradiated and non-irradiated mice, but also in healthy wild-type mice, showed signal loss on T2*w MRI. Signal loss however did not correspond with histological evidence of USPIO uptake by aortic wall but by peri-aortic lymph nodes. The versatility of USPIOs as a negative MR contrast agent for both lymph node staging and atherosclerosis may limit the use for detection of atherosclerotic lesions in vessels where lymph nodes are highly prevalent. Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.

  12. The proportion of total C18:1 trans-fatty acids in red blood cell membranes relates to carotid plaque prevalence.

    Science.gov (United States)

    Herreras, Zoe; Cofán, Montserrat; Catalan, Marta; Calvo, Carlos; Pinyol, Montserrat; Amor, Antonio J; Gilabert, Rosa; Ros, Emilio; Sala-Vila, Aleix; Ortega, Emilio

    2016-12-01

    Consistent evidence supports the pro-atherogenic properties of dietary trans-fatty acids (TFAs). However, there are no clinical data on TFA intake and atheroma plaque. We cross sectionally investigated whether the proportion of total C18:1 TFA in red blood cells (RBCs), which mirrors dietary TFA intake, independently relates to carotid plaque prevalence in subjects with new-onset type 2 diabetes mellitus without prior cardiovascular disease (n=101, 56% men, mean age 61 years) and age- and sex-matched controls (n=96). RBC fatty acid composition was determined by gas chromatography. Plaque (defined as carotid intima-media thickness ≥1.5 mm) was sonographically assessed at three bilateral carotid segments. In multivariate models adjusting for group (diabetes or control) and classical cardiovascular risk factors, for each 0.1% increase in RBC total C18:1 TFA isomers, plaque prevalence increased by 53% (P=.002). In contrast, for each 0.1% increase in RBC alpha-linolenic acid, the vegetable omega-3 fatty acid, plaque prevalence decreased by 43% (PC18:1 TFA, considered a proxy of intake, directly relates to the ultrasound feature that best predicts future cardiovascular events. Our findings support current recommendations to limit TFA intake for cardiovascular health promotion. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. [Qualitative and quantitative diagnostic performance of 320-slice computed tomography for detecting coronary artery disease with respect to atherosclerotic plaque characteristics].

    Science.gov (United States)

    Li, Suhua; Liu, Jinlai; Peng, Long; Dong, Ruimin; Wu, Huilan; Wang, Chenlin; Ni, Qiongqiong; Luo, Yanting; Zhu, Jieming; Chen, Lin

    2014-10-28

    To investigate qualitatively and quantitatively the diagnostic performance of 320-slice CT for detection of coronary artery disease with respect to different atherosclerotic plaque characteristics. A retrospective search was performed for inpatients underwent both coronary CT and further coronary angiography (CAG) from December 1, 2008 to December 31, 2012. The diagnostic performance of 320-slice CTA for detecting significant stenosis ( ≥ 50% diameter) with respect to atherosclerotic plaque characteristics were analyzed by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, kappa index (κ), and area under the receiver operating characteristic curve (AUC). Chi-square test was used to evaluate whether there were significant differences of the true-case frequency (true positive + true negative) and false-case frequency (false positive + false negative) among groups. Bland-Altman analysis was used to determine limits of agreement between CTA and CAG. A total of 454 patients and 6 779 segments were analyzed. Diagnostic accuracy was higher in non-calcified segments; whereas they decreased in the presence of both mild-moderately and heavily calcified plaques. Excellent agreement (κ = 0.810) between CT and CAG was observed for non-calcified segments, while good agreement was observed for both mild-moderately (κ = 0.701) and heavily calcified segments (κ = 0.750). Both mild-moderate (P = 0.000) and heavy (P = 0.000) calcification decreased the true-case frequency and increased the false-case frequency when compared to non-calcification. There were no significant underestimation or overestimation for non-calcified (P = 0.087) and mild-moderately calcified (P = 0.704) segments, while there was significant overestimation for heavily calcified segments (P = 0.001). Great qualitative and quantitative diagnostic performances of 320-slice CT were observed in non-calcified coronary segments. However, qualitative

  14. 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....

  15. 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

    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...

  16. Dual energy computed tomography quantification of carotid plaques calcification: comparison between monochromatic and polychromatic energies with pathology correlation

    Energy Technology Data Exchange (ETDEWEB)

    Mannelli, Lorenzo [University of Washington, Departments of Radiology, Seattle, WA (United States); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY (United States); MacDonald, Lawrence; Ferguson, Marina; Shuman, William P.; Xu, Dongxiang; Yuan, Chun; Mitsumori, Lee M. [University of Washington, Departments of Radiology, Seattle, WA (United States); Mancini, Marcello; Ragucci, Monica; Monti, Serena [IRCCS Fondazione SDN, Naples (Italy)

    2015-05-01

    We compared carotid plaque calcification detection sensitivity and apparent cross-sectional area on CT as a function of CT beam energy using conventional CT techniques and virtual mono-energetic CT images generated from dual-energy acquisitions. Five ex-vivo carotid endarterectomy (CEA) specimens were imaged with dual-energy computed tomography. Virtual monochromatic spectrum (VMS) CT images were reconstructed at energies between 40-140 keV. The same specimens were imaged using conventional polyenergetic spectrum (PS) CT with peak beam energies 80, 100, 120, and 140 kVp. The histological calcium areas on each corresponding CEA specimen were traced manually on digitized images of Toluidine-Blue/Basic-Fuchsin stained plastic sections. 40 keV VMS CT images provided high detection sensitivity (97 %) similar to conventional PS CT images (∝96 %). The calcification size measured on CT decreased systematically with increasing CT beam energy; the rate of change was larger for the VMS images than for PS images. From a single dual-energy CT, multiple VMS-CT images can be generated, yielding equivalent detection sensitivity and size correlations as conventional PS-CT in CEA calcification imaging. VMS-CT at 80-100 keV provided the most accurate estimates of calcification size, as compared to histology, but detection sensitivity was reduced for smaller calcifications on these images. (orig.)

  17. AN ULTRASONOGRAPHIC STUDY OF CAROTID ARTERY PATHOLOGY IN ISCHAEMIC STROKE PATIENTS

    Directory of Open Access Journals (Sweden)

    Puthiya Maliyakkal

    2016-03-01

    Full Text Available BACKGROUND Majority of ischaemic strokes are due to extracranial carotid artery disease. Ultrasonography of the carotid arteries is easily available, cost-effective noninvasive method of evaluation in preventing ischaemic strokes. OBJECTIVES To evaluate the carotid artery pathology, and grade the stenotic lesions by ultrasonography in ischaemic stroke patients. MATERIAL AND METHODS In 25 patients of clinically diagnosed cerebrovascular insufficiency, carotid and vertebral arteries on both sides were examined. The site, size, echogenicity, luminal narrowing and velocity changes at the site of atherosclerotic plaque was recorded. The observations in percentages were compared and analysed. RESULTS Hemiparesis was the commonest presenting complaint. Among these 25 patients, 58% of them had atheromatous plaque. Smoking had a strong association with the development of plaque. 64% of these patients with atheromatous plaque were males with a sex ratio of 1.8:1, 57% of plaques were found at carotid bifurcation predominantly on left side, 57% of these plaques had significant stenosis and one had complete occlusion. Predominant type of these plaque were strongly echogenic with calcification (52%, 35% of these patients had a PSV ratio of 2-4 and 14% >4. CONCLUSION The study showed atheromatous plaque changes with significant stenosis among cerebrovascular insufficiency patients. The findings were consistent with the other studies.

  18. Colour Doppler evaluation of extracranial carotid artery in patients presenting with features of cerebrovascular disease: A clinical and radiological correlation

    Directory of Open Access Journals (Sweden)

    Sanjeev Sehrawat

    2012-01-01

    Full Text Available Aim: To evaluate the morphological and hemodynamic changes that take place in carotid arteries by colour Doppler in patients presenting with features of stroke. Background and Objectives: Cerebrovascular accidents constitute a major cause of adult mortality. The principal indication for cerebrovascular Doppler examination is stroke prevention. Colour Doppler sonography is a sensitive method for detection of atherosclerotic plaque and provides considerable information about the extent and severity of plaque as well as the resulting diminution of arterial lumen. The main strengths of sonography of carotid arteries are patient comfort, lack of risk and accuracy in detecting carotid stenosis. Material and Methods: A prospective study of Colour Doppler in carotid arteries was carried out for 12 months from 1 st July 2009 to 1 st July 2010. The study was carried out on 40 individuals, suspected of cerebrovascular insufficiency and having one or the other risk factors for cerebrovascular disease. A detailed clinical history, CNS examination findings and evidence of hypertension, diabetes mellitus, hyperlipidemia and ischemic heart disease were noted. Carotid Doppler evaluation was done by using Siemens Antares Ultrasound system. The data gathered were grey scale and Doppler findings of common carotid artery, internal carotid artery and external carotid arteries. Doppler findings were correlated with clinical features and risk factors. Results: In our study of 40 patients, the commonest lesion found was the atherosclerotic plaque. Highest incidence of plaque was seen in males 41% in the age group of 60-70 years and in females 37% in age group of 70-80 years. Cigarette smoking was the most common risk factor (60% associated with stroke/ Transient Ischaemic Attacks (TIA. Hemiparesis was the most common presenting symptom (35% among the symptomatic cases. Atheromatous plaque was most commonly found in the right carotid system (60%. Most common site for

  19. Relationship between the Levels of MMP-9, TIMP-1, and Zinc in Biological Samples of Patients with Carotid Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Zakhro A. Usmanova

    2015-06-01

    Full Text Available The aim our study was to evaluate the levels of zinc in blood serum, hair, and specimens of carotid artery atherosclerotic plaques (CAAPs and their relationship to levels of MMP-9 and TIMP-1 in the serum of patients with stable and unstable CAAPs. Material and Methods: The study included 73 patients (55 men and 18 women aged from 46 to 88 years (mean age 65.96±1.07 years with CAAPs. The control group consisted of 10 healthy subjects of similar age and gender. Written informed consent was obtained from each patient. The patients were divided into two groups depending on their atherosclerotic plaque stability according to prior duplex ultrasonography. Group 1 consisted of 45 patients with stable atherosclerotic plaque, and Group 2 included 28 patients with unstable AP. Patients with hemodynamically significant carotid stenosis and unstable atherosclerotic plaques underwent carotid endarterectomy. The serum concentration of MMP-9 and TIMP-1 was determined using the standard test systems for immunoassay. Quantitative determination of the zinc level in hair and atherosclerotic plaque was carried out by optical emission spectrometry; the serum Zn was determined colorimetrically. Results: The serum levels of MMP-9 and TIMP-1 were significantly higher in Group 2 compared to Group1 and the control group. The index of MMP-9/TIMP-1 was 1.6 times higher in Group 2 compared to the control group. The level of Zn in serum and hair was not significantly different between Groups 1 and 2. However, Zn levels in unstable atherosclerotic plaque were lower than in the control group. Reducing the concentration of zinc in the hair was accompanied by a decrease in zinc level in atherosclerotic plaque specimens. With the progression of atherosclerosis and increasing the intima-media thickness of the common carotid artery, the level of zinc in serum and atherosclerotic plaques decreased. Increasing the serum concentration of MMP-9 was accompanied by decreasing the zinc

  20. Arteria carótida y placa "carótida un órgano" Carotid artery and plaque. "carotid: an organ"

    Directory of Open Access Journals (Sweden)

    Juan G Barrera

    2006-10-01

    Full Text Available En estos momentos es posible hacer recomendaciones sobre las indicaciones de la endarterectomía carotídea, basadas en los ensayos clínicos publicados y en la revisión de grandes series quirúrgicas. Las indicaciones para la cirugía dependerán del grado de estenosis y de la morfología de la placa, así como del estado clínico del paciente y de la morbi-mortalidad del equipo quirúrgico. Este al igual que otros estudios con grandes series de casos, evidencia que la endarterectomía carotídea y/o el manejo endovascular, realizado por equipos expertos, es un procedimiento seguro en pacientes con indicación quirúrgica.It is now possible to recommend indications for aortic endarterectomy, based on published clinical essays and revision of large surgical series. Surgery indications will depend on the stenosis degree and the plaque morphology, as well as on the patient's clinical state and the morbid-mortality in this surgical team. As other studies with large case series, evidences that carotid endarterectomy and/or endovascular management, when realized by expert teams, is a safe procedure in patients with surgical indication.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Wen-yi Wang

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

  3. Antioxidized LDL Antibodies Are Associated With Different Metabolic Pathways in Patients With Atherosclerotic Plaque and Type 2 Diabetes

    OpenAIRE

    Bernal-Lopez, M. Rosa; Garrido-Sanchez, Lourdes; Gomez-Carrillo, Victor; Gallego-Perales, Jose Luis; Llorente-Cortes, Vicenta; Calleja, Fernando; Gomez-Huelgas, Ricardo; Badimon, Lina; Tinahones, Francisco J.

    2013-01-01

    OBJECTIVE Oxidized lipoproteins and antioxidized LDL antibodies (antioxLDL abs) have been detected in human plasma and atherosclerotic lesions. The principle aim of this study was to analyze the possible relationship between IgG and IgM antioxLDL abs and factors involved in different metabolic pathways (inflammation, lipid metabolism, apoptosis, and cell cycle arrest profile) in the occluded popliteal artery (OPA) compared with the femoral vein (FV). RESEARCH DESIGN AND METHODS Fifteen patien...

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

    DEFF Research Database (Denmark)

    Karadimou, Glykeria; Folkersen, Lasse; Berg, Martin

    2016-01-01

    cells, macrophages and endothelial cells in capillaries, as shown by immunohistochemistry. In short-term tissue cultures, ex vivo treatment of plaques with the TLR7 ligand imiquimod elicited dose-dependent secretion of IL-10, TNF-α, GM-CSF, and IL-12/IL-23p40. This secretion was blocked with a TLR7...... inhibitor. Immunofluorescent tissue analysis after TLR7 stimulation showed IL-10 expression in T cells, macrophages and vascular smooth muscle cells. TLR7 mRNA levels in the plaques were correlated with IL-10 receptor (r=0.4031, p

  5. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

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    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.)

  6. Autologous Bone Marrow Mononuclear Cell Transplantation Delays Progression of Carotid Atherosclerosis in Rabbits.

    Science.gov (United States)

    Cui, Kefei; Ma, Xiao; Yu, Lie; Jiang, Chao; Fu, Chao; Fu, Xiaojie; Yu, Xiaofang; Huang, Yuanjing; Hou, Suyun; Si, Caifeng; Chen, Zhengguang; Yu, Jing; Wan, Jieru; Wang, Jian

    2016-09-01

    Bone marrow mononuclear cells (BMMNCs) can counteract oxidative stress and inhibit the inflammatory response in focal ischemic stroke models. However, the effect of BMMNC transplantation on carotid atherosclerosis needs to be determined. The carotid atherosclerotic plaque model was established in New Zealand White rabbits by balloon injury and 8 weeks of high-fat diet. Rabbits were randomized to receive an intravenous injection of autologous bromodeoxyuridine (BrdU)-labeled BMMNCs or an equal volume of phosphate-buffered saline. Plaques were evaluated for expression of proinflammatory and anti-inflammatory cytokines, anti-oxidant proteins, and markers of cell death. BMMNCs migrated into atherosclerotic plaque on the first day after cell transplantation. BMMNC-treated rabbits had smaller plaques and more collagen deposition than did the vehicle-treated controls on day 28 (p Autologous BMMNC transplantation can suppress the process of atherosclerotic plaque formation and is associated with enhanced anti-oxidative effect, reduced levels of inflammatory cytokines and cleaved caspase-3, and increased expression of insulin-like growth factor-1 and its receptor. BMMNC transplantation represents a novel approach for the treatment of carotid atherosclerosis.

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

    Science.gov (United States)

    Kim, Christine H J; Mitchell, James B; Bursill, Christina A; Sowers, Anastasia L; Thetford, Angela; Cook, John A; van Reyk, David M; Davies, Michael J

    2015-05-01

    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 in apoE-/- mice fed a high fat diet (HFD). ApoE-/- mice were fed for 12 weeks on standard chow diet or a high-fat diet. Half the mice were supplemented with 10 mg/g TEMPOL in their food. Plasma samples were analysed for triglycerides, cholesterol, low- and high-density lipoprotein 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. 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 decrease in adiponectin. TEMPOL supplementation reversed these effects. When compared to HFD-fed mice, TEMPOL supplementation increased plaque collagen content, decreased lipid content and increased macrophage numbers. These data indicate that in a well-established model of obesity-associated hyperlipidaemia and atherosclerosis, TEMPOL had a significant impact on body mass, atherosclerosis, hyperlipidaemia and inflammation. TEMPOL may therefore be of value in suppressing obesity, metabolic disorders and increasing atherosclerotic plaque stability. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Characterization of carotid artery plaque components on magnetic resonance imaging using signal intensity of the phantom as a reference.

    Science.gov (United States)

    Ogura, Akio; Hayakawa, Katsumi; Maeda, Fumie; Kajihara, Mariko; Takatsu, Yasuo; Yamamura, Ken'ichiro

    2013-12-01

    To evaluate the properties of plaque by the use of magnetic resonance imaging (MRI), it is necessary to use a material with stable signal intensity (eg, muscle or submandibular gland) as a reference. However, there may be differences between individuals. Therefore, we used a small phantom set on the circumference of the neck as a reference. The signal intensity ratio (SIR) methods using the phantom as a reference were reviewed for discrimination of the properties of plaque in the carotid artery. Three phantoms (phantom 1: water; phantom 2: 5 μmol gadopentetate dimeglumine; and phantom 3: 2.5 μmol gadopentetate dimeglumine) were set around the neck. SIR was calculated for each region of interest and compared according to pathological grade. The method using a phantom as a reference reduced the standard deviations of tissue ratios to 0.16 from 0.27 in comparison with the method using muscle and showed a close correlation with pathological grade. In addition, the agreement rates with pathological grade and grades from each SIR using signal intensity of the phantom as a reference were higher than using signal intensity of the muscle as a reference to 0.86 from 0.63 for two-dimensional images and to 0.86 from 0.71 for three-dimensional images. The method described here reduced error compared to the method using muscle as a reference, and the results were closely correlated with pathological grade. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVES: The aim of this study was to investigate whether subclinical vascular damage improved traditional risk prediction, reclassifying individuals with regard to primary prevention. METHODS: Two thousand and fifty-nine healthy individuals aged 41, 51, 61, and 71 years were divided into age,...

  10. Enhanced base excision repair capacity in carotid atherosclerosis may protect nuclear DNA but not mitochondrial DNA

    DEFF Research Database (Denmark)

    Skarpengland, Tonje; B. Dahl, Tuva; Skjelland, Mona

    2016-01-01

    Lesional and systemic oxidative stress has been implicated in the pathogenesis of atherosclerosis, potentially leading to accumulation of DNA base lesions within atherosclerotic plaques. Although base excision repair (BER) is a major pathway counteracting oxidative DNA damage, our knowledge on BER...... and accumulation of DNA base lesions in clinical atherosclerosis is scarce. Here, we evaluated the transcriptional profile of a wide spectrum of BER components as well as DNA damage accumulation in atherosclerotic and non-atherosclerotic arteries. BER gene expression levels were analyzed in 162 carotid plaques, 8...... genes in atherosclerosis may contribute to lesional nuclear DNA stability but appears insufficient to maintain mtDNA integrity, potentially influencing mitochondrial function in cells within the atherosclerotic lesion....

  11. Application of the lattice Boltzmann model to simulated stenosis growth in a two-dimensional carotid artery

    International Nuclear Information System (INIS)

    Boyd, J; Buick, J; Cosgrove, J A; Stansell, P

    2005-01-01

    The lattice Boltzmann model is used to observe changes in the velocity flow and shear stress in a carotid artery model during a simulated stenosis growth. Near wall shear stress in the unstenosed artery is found to agree with literature values. The model also shows regions of low velocity, rotational flow and low near wall shear stress along parts of the walls of the carotid artery that have been identified as being prone to atherosclerosis. These regions persist during the simulated stenosis growth, suggesting that atherosclerotic plaque build-up creates regions of flow with properties that favour atherosclerotic progression

  12. Stresses in Carotid Plaques using MRI-based Fluid Structure Interaction Models

    DEFF Research Database (Denmark)

    Samuel, Samuel Alberg; Fründ, Torben; Kim, Won Yong

    2006-01-01

    the morphology of the plaque into account. Indeed, unstable or vulnerable plaques are known to possess large lipid cores and thin fibrous caps (3). A morphology such as this generates severe internal stresses in the fibrous cap. In vitro studies have shown that cap rupture predominantly occur when static...... in the pressure outlets was set to 10666 Pa. The Neo-Hookean hyper-elastic model was used to specify the material properties (5) of surrounding tissue (µ=6.20e6, κ=1.24e8, ρ=960) and vessel wall (µ=7.20e5, κ=1.44e7, ρ=1200). Lipid was treated as an isotropic materiel (6) with Young’s modulus set to 1....../100 of that of the equivalent Young’s modulus of the vessel wall (E=1e5, ν=0.45, ρ=900). To facilitate convergence, the fluid was simulated using artificial high viscosity and low velocity which were gradually changed to the correct values. An initial simulation employing the stationary linear solver SPOOLES was performed...

  13. Expression of Egr1 and p53 in human carotid plaques and apoptosis induced by 7-oxysterol or p53.

    Science.gov (United States)

    Miah, Sayem; Zadeh, Shahram Nour Mohammad; Yuan, Xi-Ming; Li, Wei

    2013-07-01

    Egr-1 and p53 are involved in pathology of both atherosclerosis and cancer. However, it is unknown whether p53 and Egr1 are interactively involved in apoptosis in atherosclerosis. We found that in human carotid plaques, the expression of p53 was inversely correlated with Egr1. In U937 cells, 7β-hydroxycholesterol and 7-ketocholesterol induced production of reactive oxygen species (ROS), transient up-regulation of Egr1 followed by late induction of p53 and apoptosis. Cells with nuclear fragmentation induced by 7-oxysterol or p53 showed increased levels of p53, but decreased levels of Egr1. In conclusion, ROS induced by 7-oxysterols may function as an early initiator of Egr1 expression. The late induced p53 by 7-oxysterols contributes to apoptotic cell death and is linked to the reduction of Egr1 levels, which resembles the differential expression of p53 and Egr1 in human atheroma progression. Copyright © 2012 Elsevier GmbH. All rights reserved.

  14. Utility of 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines in HIV-Infected Adults With Carotid Atherosclerosis

    Science.gov (United States)

    Phan, Binh An P.; Weigel, Bernard; Ma, Yifei; Scherzer, Rebecca; Li, Danny; Hur, Sophia; Kalapus, S.C.; Deeks, Steven

    2017-01-01

    Background— Although HIV is associated with increased atherosclerotic cardiovascular disease (CVD) risk, it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. We compared the 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III recommendations in HIV-infected adults and evaluated associations with carotid artery intima-media thickness and plaque. Methods and Results— Carotid artery intima-media thickness was measured at baseline and 3 years later in 352 HIV-infected adults without clinical atherosclerotic CVD and not on statins. Plaque was defined as IMT >1.5 mm in any segment. At baseline, the median age was 43 (interquartile range, 39–49), 85% were men, 74% were on antiretroviral medication, and 50% had plaque. The American College of Cardiology/American Heart Association guidelines were more likely to recommend statins compared with the Adult Treatment Panel III guidelines, both overall (26% versus 14%; PCardiology/American Heart Association guidelines recommended statins to a greater number of HIV-infected adults compared with the Adult Treatment Panel III guidelines, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Baseline carotid atherosclerosis but not atherosclerotic CVD risk scores was an independent predictor of mortality. HIV-specific guidelines that include detection of subclinical atherosclerosis may help to identify HIV-infected adults who are at increased atherosclerotic CVD risk and may be considered for statins. PMID:28674084

  15. In-111 platelet scintigraphy: carotid atherosclerosis and stroke

    International Nuclear Information System (INIS)

    Powers, W.J.

    1984-01-01

    An association between atherosclerosis of the internal carotid artery and ischemia or infarction of the ipsilateral cerebral hemisphere has been demonstrated by numerous radiographic and pathologic studies. The precise mechanism by which carotid atherosclerosis causes these problems, however, remains unclear. Several observations suggest that fibrin-platelet thrombi form on atherosclerotic plaques in the neck arteries and then embolize distally into the intracranial circulation. Unfortunately, platelet embolization does not adequately explain a variety of clinical and pathological findings in patients with cerebrovascular disease. This editorial will discuss these findings. It is obvious that the understanding of the role of platelets in the pathogenesis of ischemic cerebrvascular disease is far from complete

  16. The Burden of Hard Atherosclerotic Plaques Does Not Promote Endoleak Development After Endovascular Aortic Aneurysm Repair: A Risk Stratification

    International Nuclear Information System (INIS)

    Petersen, Johannes; Glodny, Bernhard

    2011-01-01

    Purpose: To objectify the influence of the atherosclerotic burden in the proximal landing zone on the development of endoleaks after endovascular abdominal aortic aneurysm repair (EVAR) or thoracic endovascular aneurysm repair (TEVAR) using objective aortic calcium scoring (ACS). Materials and Methods: This retrospective observation study included 267 patients who received an aortic endograft between 1997 and 2010 and for whom preoperative computed tomography (CT) was available to perform ACS using the CT-based V600 method. The mean follow-up period was 2 ± 2.3 years. Results: Type I endoleaks persisted in 45 patients (16.9%), type II in 34 (12.7%), type III in 8 (3%), and type IV or V in 3 patients, respectively (1.1% each). ACS in patients with type I endoleaks was not increased: 0.029 ± 0.061 ml compared with 0.075 ± 0.1349 ml in the rest of the patients, (p > 0.05; Whitney–Mann U-Test). There were significantly better results for the indication “traumatic aortic rupture” than for the other indications (p < 0.05). In multivariate logistic regression analyses, age was an independent risk factor for the development of type I endoleaks in the thoracic aorta (Wald 9.5; p = 0.002), whereas ACS score was an independent protective factor (Wald 6.9; p = 0.009). In the abdominal aorta, neither age nor ACS influenced the development of endoleaks. Conclusion: Contrary to previous assumptions, TEVAR and EVAR can be carried out without increasing the risk of an endoleak of any type, even if there is a high atherosclerotic “hard-plaque” burden of the aorta. The results are significantly better for traumatic aortic.

  17. The perimenopausal atherosclerosis transition: relationships between calcified and noncalcified coronary, aortic, and carotid atherosclerosis and risk factors and hormone levels.

    Science.gov (United States)

    Munir, Jamalah A; Wu, Hongyan; Bauer, Kelly; Bindeman, Jody; Byrd, Carole; Feuerstein, Irwin M; Villines, Todd C; Taylor, Allen J

    2012-01-01

    Women of perimenopause age experience an upward transition of cardiovascular risk possibly in association with changing hormonal status. We examined the cross-sectional relationships between the atherosclerotic plaque within the coronary and carotid arteries and aorta and the menopausal hormone levels among asymptomatic perimenopausal women. The Assessment of the Transition of Hormonal Evaluation with Noninvasive Imaging of Atherosclerosis was a prospective substudy of the Prospective Army Coronary Calcium project. We screened 126 asymptomatic perimenopausal women (mean age, 50 y) using contrast-enhanced CT angiography (multidetector CT) and carotid ultrasound. Women had coronary calcium data from 5 to 10 years earlier. The measures included cardiovascular risk factors, serum hormone levels, 64-slice multidetector CT, and carotid ultrasound. The prevalence of any coronary plaque was 35.5%. The prevalence of noncalcified plaque was 30.2%, and noncalcified plaque was the only manifestation of coronary artery disease in 10.7%. Markers of androgenicity (increased free testosterone and reduced sex hormone-binding globulin) were associated with an increased extent of calcified and noncalcified coronary artery plaque and aortic plaque. However, these relationships were not independent of cardiovascular risk factors. Follicle-stimulating hormone was directly associated with the number of aortic plaques. The levels of estrogen hormones were unrelated to plaque presence or extent. Coronary, aortic, and carotid arterial plaque is prevalent in perimenopausal women without cardiac symptoms. The assessment of perimenopausal hormone status was not independently associated with subclinical atherosclerosis beyond standard cardiovascular risk factors.

  18. Relationship between markers of plaque vulnerability in optical coherence tomography and atherosclerotic progression in adult patients with heart transplantation.

    Science.gov (United States)

    Park, Kyoung-Ha; Sun, Tao; Liu, Zhi; Yang, Shi-Wei; Lennon, Ryan J; Lerman, Lilach O; Kushwaha, Sudhir S; Lerman, Amir

    2017-02-01

    Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease, and optical coherence tomography (OCT) provides detailed microstructural information. The current study was designed to test the hypothesis that markers of plaque vulnerability derived from OCT could predict CAV progression after heart transplantation (HTx). In 34 consecutive patients (median 3.1 years from HTx), intravascular ultrasound (IVUS) and OCT were performed in the left anterior descending artery (LAD) during routine annual coronary angiography. The presence of vulnerability markers, such as lipid pools, thin-cap fibroatheroma, macrophages and microchannels, was assessed in 100 consecutive frames of OCT in 20-mm segments of proximal LAD. The total number of appearances of vulnerable markers was defined as the vulnerability score (VS). Plaque volume (PV) was measured in the same study segment using IVUS at baseline and at 1-year follow-up, and the association between the baseline VS and the subsequent change in percent PV (PV / vessel volume × 100 [%PV]) was evaluated. Follow-up IVUS study was conducted after 12.5 ± 1.3 months. The mean VS was 59.9 ± 44.6. Compared with the initial %PV, the follow-up %PV increased in the study segment (25.6 ± 13.7% to 31.8 ± 17.5%, p markers of plaque vulnerability in OCT can predict the progression of CAV. Therefore, in patients with HTx, OCT may aid in determining prognosis and guiding therapy related to CAV. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  19. Does oral hygiene trigger carotid artery intima-media thickness?

    Science.gov (United States)

    Uyar, Ihsan Sami; Sahin, Veysel; Akpinar, Mehmet Besir; Abacilar, Feyzi; Okur, Faik Fevzi; Ozdemir, Ugur; Ates, Mehmet; Yasa, Elif Filiz

    2013-08-01

    The aim of this study was to evaluate whether poor oral hygiene is associated with the intima-media thickness of the carotid arteries, which is one of the predictors of future progression of subclinical atherosclerosis. We selected 108 patients during periodontal examinations according to their oral hygiene. The patients had no history of atherosclerotic disease. The results of carotid artery B-mode ultrasonography examinations were analyzed at baseline and after a mean of 7.8 months. Patients were scored on the DMFT index for the number of decayed (D), missing (M), and filled (F) teeth (T). We also used the Silness-Loe plaque index (SLI) to evaluate oral hygiene and dental plaque. The patients were divided into 2 groups according to DMFT and SLI criteria. Group I had a DMFT index of 0 to 3 and an SLI score of 0 or 1; group II had a DMFT index of 4 to 28 and an SLI score of 2 or 3. Dental status and oral hygiene were significantly associated with carotid artery intima-media thickness. Patients with increasing DMFT and SLI indices were correlated with intima-media thickness of the carotid artery. Chronic poor oral hygiene and tooth loss are related to subclinical atherosclerotic changes in the carotid arteries and might be indicative of future progression of atherosclerosis.

  20. Assessing carotid atherosclerosis by fiber-optic multispectral photoacoustic tomography

    Science.gov (United States)

    Hui, Jie; Li, Rui; Wang, Pu; Phillips, Evan; Bruning, Rebecca; Liao, Chien-Sheng; Sturek, Michael; Goergen, Craig J.; Cheng, Ji-Xin

    2015-03-01

    Atherosclerotic plaque at the carotid bifurcation is the underlying cause of the majority of ischemic strokes. Noninvasive imaging and quantification of the compositional changes preceding gross anatomic changes within the arterial wall is essential for diagnosis of disease. Current imaging modalities such as duplex ultrasound, computed tomography, positron emission tomography are limited by the lack of compositional contrast and the detection of flow-limiting lesions. Although high-resolution magnetic resonance imaging has been developed to characterize atherosclerotic plaque composition, its accessibility for wide clinical use is limited. Here, we demonstrate a fiber-based multispectral photoacoustic tomography system for excitation of lipids and external acoustic detection of the generated ultrasound. Using sequential ultrasound imaging of ex vivo preparations we achieved ~2 cm imaging depth and chemical selectivity for assessment of human arterial plaques. A multivariate curve resolution alternating least squares analysis method was applied to resolve the major chemical components, including intravascular lipid, intramuscular fat, and blood. These results show the promise of detecting carotid plaque in vivo through esophageal fiber-optic excitation of lipids and external acoustic detection of the generated ultrasound. This imaging system has great potential for serving as a point-ofcare device for early diagnosis of carotid artery disease in the clinic.

  1. 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.

  2. Protective role of parnaparin in reducing systemic inflammation and atherosclerotic plaque formation in ApoE-/- mice.

    Science.gov (United States)

    Artico, Marco; Riganò, Rachele; Buttari, Brigitta; Profumo, Elisabetta; Ionta, Brunella; Bosco, Sandro; Rasile, Manuela; Bianchi, Enrica; Bruno, Moira; Fumagalli, Lorenzo

    2011-04-01

    Atherosclerosis is a degenerative disease whose role in the onset and development of cardiovascular pathologies and complications is of importance. Due to its silent but progressive development, and considering the endothelial, immunological and inflammatory processes that are involved in its clinical course, this still relatively unknown pathological condition has been and continues to be a matter of investigation worldwide. Our experience with previous studies on atherosclerosis led us to investigate the possible influence of a low molecular weight heparin (LMWH) - Parnaparin® on the development and clinical course of atherosclerosis in double knock-out laboratory animals (ApoE-/- mice). Our experiments demonstrated a possible role of Parnaparin (PNP) in the control of atherogenic disease. In fact, in treated mice vs. untreated ones, PNP reduced the number and the size of atherosclerotic lesions in the aortic wall, as well as the development of liver steatosis, which was massive in untreated animals and moderate in treated ones. These preliminary observations require further clinical studies, but demonstrate a possible role of Parnaparin in the control of the development and clinical evolution of atherosclerosis and liver steatosis in laboratory animals.

  3. The lipid-rich core region of human atherosclerotic fibrous plaques. Prevalence of small lipid droplets and vesicles by electron microscopy.

    Science.gov (United States)

    Guyton, J. R.; Klemp, K. F.

    1989-01-01

    Abundant extracellular lipid deposits are associated with cell necrosis and tissue weakening in the core region of human atherosclerotic fibrous plaques. The ultrastructural morphology of the core region, previously undefined because of lipid extraction artifacts, was studied with the aid of new osmium-thiocarbohydrazide-osmium and osmium-tannic acid-paraphenylenediamine sequences for tissue processing. Small droplets of neutral lipid (30 to 400 nm profile diameter) and lipid vesicles with aqueous centers accounted for more than 90% of the area occupied by lipid-rich structures in the core region. No foam cells were present. Cholesterol crystals, lipid droplets of a size similar to those in foam cells (0.4 to 6 mu), and larger neutral lipid deposits (greater than 6 mu) together occupied less than 10% of the total area of lipid structures. Abundant lipid vesicles were associated with the nearby presence of cholesterol crystals, whereas small lipid droplets were predominant in areas without crystals. Many droplets had surface defects in the form of pits and vesicular blebs. These morphologic findings are explained most concisely by postulating direct accumulation of extracellular lipid from interstitial lipoproteins as a major process in core region formation. Moreover, a dynamic state of ongoing physical/metabolic transformation of extracellular lipid deposits is suggested. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 Figure 8 Figure 9 PMID:2646938

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Science.gov (United States)

    Bouvier, Adeline; Deleaval, Flavien; Doyley, Marvin M.; Yazdani, Saami K.; Finet, Gérard; Le Floc'h, Simon; Cloutier, Guy; Pettigrew, Roderic I.; Ohayon, Jacques

    2013-12-01

    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.

  6. 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

  7. Yellow wine polyphenolic compounds inhibit matrix metalloproteinase-2, -9 expression and improve atherosclerotic plaque in LDL-receptor-knockout mice.

    Science.gov (United States)

    Zhai, Xiaoya; Chi, Jufang; Tang, Weiliang; Ji, Zheng; Zhao, Fei; Jiang, Chengjian; Lv, Haitao; Guo, Hangyuan

    2014-01-01

    Many epidemiological studies have strongly suggested an inverse correlation between dietary polyphenol consumption and reduced risks of cardiovascular diseases. Yellow rice wine is a Chinese specialty and one of the three most ancient wines in the world (Shaoxing rice wine, beer, and grape wine). There is a large amount of polyphenol substances in yellow rice wine. This experiment was designed to study the potential beneficial effects of yellow wine polyphenolic compounds (YWPC) from yellow rice wine on progression of atherosclerosis in vivo and to further explore its underlying mechanisms. Six-week-old male LDL-receptor-knockout mice were treated with high-fat diet to establish the mouse model with atherosclerosis. Animals received 10, 30, or 50 mg/kg per day of YWPC or 10 mg/kg per day rosuvastatin or water (vehicle) for 14 weeks. The results indicated that YWPC and rosuvastatin significantly decreased circulating total cholesterol and low-density lipoprotein cholesterol. Compared to the control group, the atherosclerosis lesion area in the rosuvastatin-intervention group and YWPC at doses of 10, 30, and 50 mg/kg per day intervention groups decreased by 74.14%, 18.51%, 40.09%, and 38.42%, respectively. YWPC and rosuvastatin decreased the expression and activity of matrix metalloproteinases (MMP)-2, 9, whereas the expression of the endogenous inhibitors of these proteins, namely, tissue inhibitors of matrix metalloproteinases (TIMP)-1, 2, increased when compared to the control group. It can be concluded that the YWPC is similar to the benefic effects of rosuvastatin on cardiovascular system. These effects may be attributed to their anti-atherosclerotic actions by lowering lipid and modulating the activity and expression of MMP-2, 9 and TIMP-1, 2.

  8. David M. Hume Memorial Lecture. An overview of the stroke problem in the carotid territory.

    Science.gov (United States)

    Callow, A D

    1980-08-01

    In a review of 1,000 carotid endarterectomies performed over a 20 year period, there was relief of transient ischemic attacks in approximately 85% of patients, an operative mortality of 1.3%, due almost exclusively to myocardial infarction, and a recurrent stenosis rate of 3.1%. Coexisting cardiac disease constitutes the greatest operative hazard. Continuous electroencephalographic monitoring is a reliable method of detecting inadequate cerebral perfusion during carotid cross clamping and for the selective use of a temporary inlying carotid shunt. An atherosclerotic plaque in the carotid system constitutes a greater risk than elsewhere in the peripheral arterial system and should not be considered an innocent lesion. Prophylactic carotid endarterectomy can be performed with almost no mortality and morbidity. Antiplatelet agents, while useful in reducing the incidence of transient ischemic attacks, do not seem to provide equal protection against stroke and death from stroke.

  9. What do carotid intima-media thickness and plaque add to the prediction of stroke and cardiovascular disease risk in older adults? The cardiovascular health study.

    Science.gov (United States)

    Gardin, Julius M; Bartz, Traci M; Polak, Joseph F; O'Leary, Daniel H; Wong, Nathan D

    2014-09-01

    The aim of this study was to evaluate whether the addition of ultrasound carotid intima-media thickness (CIMT) measurements and risk categories of plaque help predict incident stroke and cardiovascular disease (CVD) in older adults. Carotid ultrasound studies were recorded in the multicenter Cardiovascular Health Study. CVD was defined as coronary heart disease plus heart failure plus stroke. Ten-year risk prediction Cox proportional-hazards models for stroke and CVD were calculated using Cardiovascular Health Study-specific coefficients for Framingham risk score factors. Categories of CIMT and CIMT plus plaque were added to Framingham risk score prediction models, and categorical net reclassification improvement (NRI) and Harrell's c-statistic were calculated. In 4,384 Cardiovascular Health Study participants (61% women, 14% black; mean baseline age, 72 ± 5 years) without CVD at baseline, higher CIMT category and the presence of plaque were both associated with higher incidence rates for stroke and CVD. The addition of CIMT improved the ability of Framingham risk score-type risk models to discriminate cases from noncases of incident stroke and CVD (NRI = 0.062, P = .015, and NRI = 0.027, P adults, the addition of CIMT modestly improves 10-year risk prediction for stroke and CVD beyond a traditional risk factor model, mainly by down-classifying risk in those without stroke or CVD; the addition of plaque to CIMT adds no statistical benefit in the overall cohort, although there is evidence of down-classification in those without events. Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  10. ADMA/SDMA in Elderly Subjects with Asymptomatic Carotid Atherosclerosis: Values and Site-Specific Association

    Directory of Open Access Journals (Sweden)

    Graziano Riccioni

    2014-04-01

    Full Text Available Asymmetric dimethylarginine (ADMA is an endogenous nitric oxide synthase (NOS inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT and plaque in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI. All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque (p < 0.001, with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p < 0.001. High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects.

  11. ADMA/SDMA in Elderly Subjects with Asymptomatic Carotid Atherosclerosis: Values and Site-Specific Association

    Science.gov (United States)

    Riccioni, Graziano; Scotti, Luca; D’Orazio, Nicolantonio; Gallina, Sabina; Speziale, Giuseppe; Speranza, Lorenza; Bucciarelli, Tonino

    2014-01-01

    Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque) (p < 0.001), with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p < 0.001). High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects. PMID:24739810

  12. 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.

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2016-07-01

    Full Text Available 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

  13. PCA-based polling strategy in machine learning framework for coronary artery disease risk assessment in intravascular ultrasound: A link between carotid and coronary grayscale plaque morphology.

    Science.gov (United States)

    Araki, Tadashi; Ikeda, Nobutaka; Shukla, Devarshi; Jain, Pankaj K; Londhe, Narendra D; Shrivastava, Vimal K; Banchhor, Sumit K; Saba, Luca; Nicolaides, Andrew; Shafique, Shoaib; Laird, John R; Suri, Jasjit S

    2016-05-01

    Percutaneous coronary interventional procedures need advance planning prior to stenting or an endarterectomy. Cardiologists use intravascular ultrasound (IVUS) for screening, risk assessment and stratification of coronary artery disease (CAD). We hypothesize that plaque components are vulnerable to rupture due to plaque progression. Currently, there are no standard grayscale IVUS tools for risk assessment of plaque rupture. This paper presents a novel strategy for risk stratification based on plaque morphology embedded with principal component analysis (PCA) for plaque feature dimensionality reduction and dominant feature selection technique. The risk assessment utilizes 56 grayscale coronary features in a machine learning framework while linking information from carotid and coronary plaque burdens due to their common genetic makeup. This system consists of a machine learning paradigm which uses a support vector machine (SVM) combined with PCA for optimal and dominant coronary artery morphological feature extraction. Carotid artery proven intima-media thickness (cIMT) biomarker is adapted as a gold standard during the training phase of the machine learning system. For the performance evaluation, K-fold cross validation protocol is adapted with 20 trials per fold. For choosing the dominant features out of the 56 grayscale features, a polling strategy of PCA is adapted where the original value of the features is unaltered. Different protocols are designed for establishing the stability and reliability criteria of the coronary risk assessment system (cRAS). Using the PCA-based machine learning paradigm and cross-validation protocol, a classification accuracy of 98.43% (AUC 0.98) with K=10 folds using an SVM radial basis function (RBF) kernel was achieved. A reliability index of 97.32% and machine learning stability criteria of 5% were met for the cRAS. This is the first Computer aided design (CADx) system of its kind that is able to demonstrate the ability of coronary

  14. Changes in ultrasound-assessed carotid intima-media thickness and plaque with a Mediterranean diet: a substudy of the PREDIMED trial.

    Science.gov (United States)

    Sala-Vila, Aleix; Romero-Mamani, Edwin-Saúl; Gilabert, Rosa; Núñez, Isabel; de la Torre, Rafael; Corella, Dolores; Ruiz-Gutiérrez, Valentina; López-Sabater, María-Carmen; Pintó, Xavier; Rekondo, Javier; Martínez-González, Miguel-Ángel; Estruch, Ramon; Ros, Emilio

    2014-02-01

    The Prevención con Dieta Mediterránea (PREDIMED) trial showed that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or 30 g/d of mixed nuts reduced incident cardiovascular events compared with a control (low fat) diet. The mechanisms of cardiovascular protection afforded by MedDiets remain to be uncovered. We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height, the ultrasound features that best predict future cardiovascular events, in subjects at high cardiovascular risk. In a PREDIMED subcohort (n=175), plaque height and carotid IMT of 3 prespecified segments (ICA, bifurcation, and common) were sonographically assessed at baseline and after intervention for a mean of 2.4 years. We evaluated 164 subjects with complete data. In a multivariate model, mean ICA-IMT progressed in the control diet group (mean [95% confidence interval], 0.052 mm [-0.014 to 0.118 mm]), whereas it regressed in the MedDiet+nuts group (-0.084 mm [-0.158 to -0.010 mm]; P=0.024 versus control). Similar results were observed for maximum ICA-IMT (control, 0.188 mm [0.077 to 0.299 mm]; MedDiet+nuts, -0.030 mm [-0.153 to 0.093 mm]; P=0.034) and maximum plaque height (control, 0.106 mm [0.001 to 0.210 mm]; MedDiet+nuts, -0.091 mm [-0.206 to 0.023 mm]; P=0.047). There were no changes in ICA-IMT or plaque after the MedDiet+extra virgin olive oil. Compared with a control diet, consumption of a MedDiet supplemented with nuts is associated with delayed progression of ICA-IMT and plaque. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial. http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.

  15. Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice.

    Science.gov (United States)

    Nencioni, Alessio; da Silva, Rafaela F; Fraga-Silva, Rodrigo A; Steffens, Sabine; Fabre, Mathias; Bauer, Inga; Caffa, Irene; Magnone, Mirko; Sociali, Giovanna; Quercioli, Alessandra; Pelli, Graziano; Lenglet, Sébastien; Galan, Katia; Burger, Fabienne; Vázquez Calvo, Sara; Bertolotto, Maria; Bruzzone, Santina; Ballestrero, Alberto; Patrone, Franco; Dallegri, Franco; Santos, Robson A; Stergiopulos, Nikolaos; Mach, François; Vuilleumier, Nicolas; Montecucco, Fabrizio

    2014-02-01

    Pharmacological treatments targeting CXC chemokines and the associated neutrophil activation and recruitment into atherosclerotic plaques hold promise for treating cardiovascular disorders. Therefore, we investigated whether FK866, a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with anti-inflammatory properties that we recently found to reduce neutrophil recruitment into the ischaemic myocardium, would exert beneficial effects in a mouse atherosclerosis model. Atherosclerotic plaque formation was induced by carotid cast implantation in ApoE-/- mice that were fed with a Western-type diet. FK866 or vehicle were administrated intraperitoneally from week 8 until week 11 of the diet. Treatment with FK866 reduced neutrophil infiltration and MMP-9 content and increased collagen levels in atherosclerotic plaques compared to vehicle. No effect on other histological parameters, including intraplaque lipids or macrophages, was observed. These findings were associated with a reduction in both systemic and intraplaque CXCL1 levels in FK866-treated mice. In vitro, FK866 did not affect MMP-9 release by neutrophils, but it strongly reduced CXCL1 production by endothelial cells which, in the in vivo model, were identified as a main CXCL1 source at the plaque level. CXCL1 synthesis inhibition by FK866 appears to reflect interference with nuclear factor-κB signalling as shown by reduced p65 nuclear levels in endothelial cells pre-treated with FK866. In conclusion, pharmacological inhibition of NAMPT activity mitigates inflammation in atherosclerotic plaques by reducing CXCL1-mediated activities on neutrophils. These results support further assessments of NAMPT inhibitors for the potential prevention of plaque vulnerability.

  16. Microparticles of Human Atherosclerotic Plaques Enhance the Shedding of the Tumor Necrosis Factor-α Converting Enzyme/ADAM17 Substrates, Tumor Necrosis Factor and Tumor Necrosis Factor Receptor-1

    Science.gov (United States)

    Canault, Matthias; Leroyer, Aurélie S.; Peiretti, Franck; Lesèche, Guy; Tedgui, Alain; Bonardo, Bernadette; Alessi, Marie-Christine; Boulanger, Chantal M.; Nalbone, Gilles

    2007-01-01

    Human atherosclerotic plaques express the metalloprotease tumor necrosis factor (TNF)-α converting enzyme (TACE/ADAM-17), which cleaves several transmembrane proteins including TNF and its receptors (TNFR-1 and TNFR-2). Plaques also harbor submicron vesicles (microparticles, MPs) released from plasma membranes after cell activation or apoptosis. We sought to examine whether TACE/ADAM17 is present on human plaque MPs and whether these MPs would affect TNF and TNFR-1 cellular shedding. Flow cytometry analysis detected 12,867 ± 2007 TACE/ADAM17+ MPs/mg of plaques isolated from 25 patients undergoing endarterectomy but none in healthy human internal mammary arteries. Plaque MPs harbored mainly mature active TACE/ADAM17 and dose dependently cleaved a pro-TNF mimetic peptide, whereas a preferential TACE/ADAM17 inhibitor (TMI-2) and recombinant TIMP-3 prevented this cleavage. Plaque MPs increased TNF shedding from the human cell line ECV-304 overexpressing TNF (ECV-304TNF), as well as TNFR-1 shedding from activated human umbilical vein endothelial cells or ECV-304TNF cells, without affecting TNF or TNFR-1 synthesis. MPs also activated the shedding of the endothelial protein C receptor from human umbilical vein endothelial cells. All these effects were inhibited by TMI-2. The present study shows that human plaque MPs carry catalytically active TACE/ADAM17 and significantly enhance the cell surface processing of the TACE/ADAM17 substrates TNF, TNFR-1, and endothelial protein C receptor, suggesting that TACE/ADAM17+ MPs could regulate the inflammatory balance in the culprit lesion. PMID:17872973

  17. Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Sharma, Ravi K; Donekal, Sirisha; Rosen, Boaz D; Tattersall, Matthew C; Volpe, Gustavo J; Ambale-Venkatesh, Bharath; Nasir, Khurram; Wu, Colin O; Polak, Joseph F; Korcarz, Claudia E; Stein, James H; Carr, James; Watson, Karol E; Bluemke, David A; Lima, João A C

    2015-04-01

    The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    OpenAIRE

    Huang, Xueying; Teng, Zhongzhao; Canton, Gador; Ferguson, Marina; Yuan, Chun; Tang, Dalin

    2010-01-01

    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...

  19. Toward the detection of intraplaque hemorrhage in carotid artery lesions using photoacoustic imaging

    Science.gov (United States)

    Arabul, Mustafa Umit; Heres, Maarten; Rutten, Marcel C. M.; van Sambeek, Marc R.; van de Vosse, Frans N.; Lopata, Richard G. P.

    2017-04-01

    Photoacoustic imaging (PAI) may have the ability to reveal the composition and the anatomical structure of carotid plaques, which determines its mechanical properties and vulnerability. We used PAI and plane wave ultrasound (PUS) imaging to obtain three-dimensional (3-D) images of endarterectomy samples ex vivo and compared the results with histology to investigate the potential of PAI-based identification of intraplaque hemorrhage. Seven carotid plaque samples were obtained from patients undergoing carotid endarterectomy and imaged with a fully integrated hand-held photoacoustic (PA) probe, consisting of a pulsed diode laser (tpulse=130 ns, Epulse=1 mJ, λ=808 nm) and a linear array transducer (fc=7.5 MHz). The samples were rotated 360 deg with 10 deg steps, and data were spatially compounded to obtain complete 3-D images of the plaques. Areas of high absorption in the 3-D datasets were identified and compared to histological data of the plaques. Data in six out of seven endarterectomy samples revealed the presence of intraplaque hemorrhages that were not visible in the PUS images. Due to the noninvasive nature of PAI, this ex vivo study may elucidate preclinical studies toward the in vivo, noninvasive, vulnerability assessment of the atherosclerotic carotid plaque.

  20. Targeting macrophage Histone deacetylase 3 stabilizes atherosclerotic lesions

    NARCIS (Netherlands)

    Hoeksema, Marten A.; Gijbels, Marion J. J.; van den Bossche, Jan; van der Velden, Saskia; Sijm, Ayestha; Neele, Annette E.; Seijkens, Tom; Stöger, J. Lauran; Meiler, Svenja; Boshuizen, Marieke C. S.; Dallinga-Thie, Geesje M.; Levels, Johannes H. M.; Boon, Louis; Mullican, Shannon E.; Spann, Nathanael J.; Cleutjens, Jack P.; Glass, Chris K.; Lazar, Mitchell A.; de Vries, Carlie J. M.; Biessen, Erik A. L.; Daemen, Mat J. A. P.; Lutgens, Esther; de Winther, Menno P. J.

    2014-01-01

    Macrophages are key immune cells found in atherosclerotic plaques and critically shape atherosclerotic disease development. Targeting the functional repertoire of macrophages may hold novel approaches for future atherosclerosis management. Here, we describe a previously unrecognized role of the

  1. Acute perioperative-stress-induced increase of atherosclerotic plaque volume and vulnerability to rupture in apolipoprotein-E-deficient mice is amenable to statin treatment and IL-6 inhibition

    Directory of Open Access Journals (Sweden)

    Henrike Janssen

    2015-09-01

    Full Text Available Myocardial infarction and stroke are frequent after surgical procedures and consume a considerable amount of benefit of surgical therapy. Perioperative stress, induced by surgery, is composed of hemodynamic and inflammatory reactions. The effects of perioperative stress on atherosclerotic plaques are ill-defined. Murine models to investigate the influence of perioperative stress on plaque stability and rupture are not available. We developed a model to investigate the influence of perioperative stress on plaque growth and stability by exposing apolipoprotein-E-deficient mice, fed a high cholesterol diet for 7 weeks, to a double hit consisting of 30 min of laparotomy combined with a substantial blood loss (approximately 20% of total blood volume; 400 µl. The innominate artery was harvested 72 h after the intervention. Control groups were sham and baseline controls. Interleukin-6 (IL-6 and serum amyloid A (SAA plasma levels were determined. Plaque load, vascular smooth muscle cell (VSMC and macrophage content were quantified. Plaque stability was assessed using the Stary score and frequency of signs of plaque rupture were assessed. High-dose atorvastatin (80 mg/kg body weight/day was administered for 6 days starting 3 days prior to the double hit. A single dose of an IL-6-neutralizing antibody or the fusion protein gp130-Fc selectively targeting IL-6 trans-signaling was subcutaneously injected. IL-6 plasma levels increased, peaking at 6 h after the intervention. SAA levels peaked at 24 h (n=4, P<0.01. Plaque volume increased significantly with the double hit compared to sham (n=8, P<0.01. More plaques were scored as complex or bearing signs of rupture after the double hit compared to sham (n=5-8, P<0.05. Relative VSMC and macrophage content remained unchanged. IL-6-inhibition or atorvastatin, but not blocking of IL-6 trans-signaling, significantly decreased plaque volume and complexity (n=8, P<0.01. Using this model, researchers

  2. [Regional and peripheral arterial stiffness measured by pOpmetre® in patients with Cvx risk factor, link with carotid plaques].

    Science.gov (United States)

    Hallab, M; Collette, M; Terrier-Barbeau, C; Legrand, M; Ducluzeau, P-H; Berrut, G; Lefthériotis, G

    2013-06-01

    Aortic stiffness is a functional and structural consequence of ageing and arteriosclerosis. Regional arterial stiffness can be easily evaluated using pOpmetre(®) (Axelife SAS, France). This new technique assesses the pulse wave transit time (TT) between the finger (TTf) and the toe (TTt). Based on height chart, regional pulse wave velocity (PWV) between the toe and the finger can be estimated (PWVtf). pOpscore(®) index is also calculated as the ratio between PWVtoe and PWVfinger and can be considered as a peripheral vascular stiffness index. The aim of the study was to evaluate the relationship between pOpmetre(®) indices and the presence of carotid plaques in a population with cardiovascular risk factors. In 77 consecutive patients recruited for a vascular screening for atherosclerosis (46 men aged 54 ± 2 years; 31 women aged 49 ± 3 years; ns), the difference between TTt and TTf (called Dt-f), the regional pulse wave velocity between the toe and the finger (PWVtf = constant × height/Dt-fm/s) and pOpscore(®) were measured by pOpmetre(®). Presence of carotid plaques was assessed using ultrasound imaging. The local aortic stiffness (AoStiff) was evaluated by the Physioflow(®) system. No difference was found between patients with or without carotid plaques (n=25 versus 52) for Ankle-Brachial Pressure Index (ABPI: 1.15 ± 0.04 versus 1.12 ± 0.03), nor for diastolic or systolic blood pressure (87 ± 3 versus 82 ± 2; 137 ± 3 versus 132 ± 2 mmHg). The first group was older than the second (59 ± 2 versus 49 ± 2 years, P<0.002) with a larger intimae media thickness (0.69 ± 0.02 versus 0.63 ± 0.01 mm, P<0.004), a higher AoStiff (10.4 ± 0.7 versus 8.2 ± 0.5m/s, P<0.02), and PWVtf (14.3 ± 1.0 versus 10.7 ± 0.7 m/s, P<0.004) and a shorter Dt-f (57.9 ± 5.1 versus 73.5 ± 3.5 ms, P<0.01). PWVtf (r(2)=0.49, P<0.0001) and Dt-f (r(2)=0.54, P<0.0001) correlated with age. A significant difference in pOpscore(®) index was observed between both groups (1.51 ± 0

  3. Definition of common carotid wall thickness affects risk classification in relation to degree of internal carotid artery stenosis: the Plaque At RISK (PARISK) study.

    Science.gov (United States)

    Steinbuch, J; van Dijk, A C; Schreuder, Fhbm; Truijman, Mtb; Hendrikse, J; Nederkoorn, P J; van der Lugt, A; Hermeling, E; Hoeks, Apg; Mess, W H

    2017-04-04

    Mean or maximal intima-media thickness (IMT) is commonly used as surrogate endpoint in intervention studies. However, the effect of normalization by surrounding or median IMT or by diameter is unknown. In addition, it is unclear whether IMT inhomogeneity is a useful predictor beyond common wall parameters like maximal wall thickness, either absolute or normalized to IMT or lumen size. We investigated the interrelationship of common carotid artery (CCA) thickness parameters and their association with the ipsilateral internal carotid artery (ICA) stenosis degree. CCA thickness parameters were extracted by edge detection applied to ultrasound B-mode recordings of 240 patients. Degree of ICA stenosis was determined from CT angiography. Normalization of maximal CCA wall thickness to median IMT leads to large variations. Higher CCA thickness parameter values are associated with a higher degree of ipsilateral ICA stenosis (p risk marker for having moderate ipsilateral ICA stenosis (>50%), 55 arteries (15%) are reclassified to another risk category. It is more reasonable to normalize maximal wall thickness to end-diastolic diameter rather than to IMT, affecting risk classification and suggesting modification of the Mannheim criteria. Clinical trials.gov NCT01208025 .

  4. Biomarkers related to carotid intima-media thickness and plaques in long-term survivors of ischemic stroke

    OpenAIRE

    Waje-Andreassen, Ulrike; Næss, Halvor; Thomassen, Lars; Marøy, Tove Helene; Mazengia, Kibret Yimer; Eide, Geir Egil; Vedeler, Christian A.

    2015-01-01

    Lifestyle risk factors, inflammation and genetics play a role in the development of atherosclerosis. We therefore studied Fc gamma receptor (FcγR) polymorphisms, interleukin (IL)-10 polymorphisms and other biomarkers related to carotid intima-media thickness (cIMT) in patients with ischemic stroke at a young age. Patients were evaluated 12 years after stroke occurrence. Patients (n = 232) 49 years of age or younger with an index stroke between 1988 and 1997 were retrospectively selected. Bloo...

  5. Diagnóstico y tratamiento de la enfermedad carotídea aterosclerótica extracraneal asintomática Diagnosis and treatment of asymptomatic extracranial atherosclerotic carotid artery disease

    Directory of Open Access Journals (Sweden)

    Luciano A. Sposato

    2011-12-01

    Full Text Available La enfermedad aterosclerótica asintomática de la arteria carótida interna extracraneal alcanza una prevalencia de hasta el 12.5%. La angioplastia carotídea todavía no ha demostrado ser lo suficientemente segura y eficaz para prevenir el ACV isquémico en estos pacientes. Estudios aleatorizados demostraron que la endarterectomía carotídea es superior al tratamiento médico en cuanto a reducción del riesgo de ACV isquémico si es realizada por equipos con tasas de complicaciones (ACV o muerte menores que 3%. Sin embargo, los pacientes evaluados en estos estudios comenzaron a reclutarse hace más de 25 años, cuando la utilización de antiagregantes plaquetarios era menor que la actual, el tratamiento de la hipertensión arterial era menos efectivo y todavía no se usaban estatinas como componentes fundamentales de los esquemas de prevención vascular. La optimización de la calidad del tratamiento médico en las últimas décadas ha llevado a una significativa reducción del riesgo de ACV en pacientes no intervenidos quirúrgicamente. En base a estas observaciones y con la excepción de casos específicos, el tratamiento médico es la opción terapéutica de elección en pacientes con enfermedad aterosclerótica carotídea extracraneal asintomática.The reported prevalence of asymptomatic atherosclerotic disease of the extracranial internal carotid artery is up to 12.5%. Carotid angioplasty has not yet proven safe and effective enough to prevent ischemic stroke in these patients. Randomized studies showed that carotid endarterectomy is superior to medical therapy in reducing the risk of ischemic stroke when performed by surgical teams with complication rates (stroke or death of less than 3%. However, recruitment of these patients began more than 25 years ago, when the use of antiplatelet agents was lower than today, the treatment of hypertension was less effective than currently, and statins were not considered as key components of

  6. Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

    Science.gov (United States)

    2013-01-01

    Background The features of carotid atherosclerosis in ketosis-onset diabetes have not been investigated. Our aim was to evaluate the prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed Chinese diabetic patients with ketosis but without islet-associated autoantibodies. Methods In total, 423 newly diagnosed Chinese patients with diabetes including 208 ketosis-onset diabetics without islet-associated autoantibodies, 215 non-ketotic type 2 diabetics and 79 control subjects without diabetes were studied. Carotid atherosclerosis was defined as the presence of atherosclerotic plaques in any of the carotid vessel segments. Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on Doppler ultrasound examination. The clinical features of carotid atherosclerotic lesions were analysed, and the risk factors associated with carotid atherosclerosis were evaluated using binary logistic regression in patients with diabetes. Results The prevalence of carotid atherosclerosis was significantly higher in the ketosis-onset diabetic group (30.80%) than in the control group (15.2%, p=0.020) after adjusting for age- and sex-related differences, but no significant difference was observed in comparison to the non-ketotic diabetic group (35.8%, p=0.487). The mean CIMT of the ketosis-onset diabetics (0.70±0.20 mm) was markedly higher than that of the control subjects (0.57±0.08 mm, pketosis-onset and the non-ketotic diabetes, the prevalence of carotid atherosclerosis was markedly increased with age (both pketosis-onset diabetics, the presence of carotid atherosclerosis was significantly associated with age, hypertension, low-density lipoprotein cholesterol and mean CIMT. Conclusions The prevalence and risk of carotid atherosclerosis were significantly higher in the ketosis-onset diabetics than in the control subjects but similar to that in the non-ketotic type 2

  7. Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery

    NARCIS (Netherlands)

    Pasterkamp, G.; Schoneveld, A. H.; Hijnen, D. J.; de Kleijn, D. P.; Teepen, H.; van der Wal, A. C.; Borst, C.

    2000-01-01

    Atherosclerotic luminal narrowing is determined by plaque mass and the mode of geometrical remodeling. Recently, we reported that the type of atherosclerotic remodeling is associated with the presence of histological markers for plaque vulnerability. Inflammation and matrix degrading proteases

  8. Prediction of fibre architecture and adaptation in diseased carotid bifurcations.

    LENUS (Irish Health Repository)

    Creane, Arthur

    2011-12-01

    Many studies have used patient-specific finite element models to estimate the stress environment in atherosclerotic plaques, attempting to correlate the magnitude of stress to plaque vulnerability. In complex geometries, few studies have incorporated the anisotropic material response of arterial tissue. This paper presents a fibre remodelling algorithm to predict the fibre architecture, and thus anisotropic material response in four patient-specific models of the carotid bifurcation. The change in fibre architecture during disease progression and its affect on the stress environment in the plaque were predicted. The mean fibre directions were assumed to lie at an angle between the two positive principal strain directions. The angle and the degree of dispersion were assumed to depend on the ratio of principal strain values. Results were compared with experimental observations and other numerical studies. In non-branching regions of each model, the typical double helix arterial fibre pattern was predicted while at the bifurcation and in regions of plaque burden, more complex fibre architectures were found. The predicted change in fibre architecture in the arterial tissue during plaque progression was found to alter the stress environment in the plaque. This suggests that the specimen-specific anisotropic response of the tissue should be taken into account to accurately predict stresses in the plaque. Since determination of the fibre architecture in vivo is a difficult task, the system presented here provides a useful method of estimating the fibre architecture in complex arterial geometries.

  9. IAP survivin regulates atherosclerotic macrophage survival

    NARCIS (Netherlands)

    Blanc-Brude, Olivier P.; Teissier, Elisabeth; Castier, Yves; Lesèche, Guy; Bijnens, Ann-Pascal; Daemen, Mat; Staels, Bart; Mallat, Ziad; Tedgui, Alain

    2007-01-01

    Inflammatory macrophage apoptosis is critical to atherosclerotic plaque formation, but its mechanisms remain enigmatic. We hypothesized that inhibitor of apoptosis protein (IAP) survivin regulates macrophage death in atherosclerosis. Western blot analysis revealed discrete survivin expression in

  10. 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.)

  11. Differential incremental value of ultrasound carotid intima-media thickness, carotid plaque, and cardiac calcium to predict angiographic coronary artery disease across Framingham risk score strata in the APRES multicentre study.

    Science.gov (United States)

    Gaibazzi, Nicola; Rigo, Fausto; Facchetti, Rita; Carerj, Scipione; Giannattasio, Cristina; Moreo, Antonella; Mureddu, Gian Francesco; Salvetti, Massimo; Grolla, Elisabetta; Faden, Giacomo; Cesana, Francesca; Faggiano, Pompilio

    2016-09-01

    According to recent data, more accurate selection of patients undergoing coronary angiography for suspected coronary artery disease (CAD) is needed. From the Active PREvention Study multicentre prospective study, we further analyse whether carotid intima-media thickness (cIMT), carotid plaques (cPL), and echocardiographic cardiac calcium score (eCS) have incremental discriminatory and reclassification predictive value for CAD over clinical risk score in subjects undergoing coronary angiography, specifically depending on their low, intermediate, or high class of clinical risk. In eight centres, 445 subjects without history of prior CAD but with chest pain of recent onset and/or a positive/inconclusive stress test for ischaemia prospectively underwent clinically indicated elective coronary angiography after cardiac and carotid ultrasound assessments with measurements of cIMT, cPL, and eCS. The study population was divided into subjects at low (10%), intermediate (10-20%), and high (>20%) Framingham risk score (FRS). Ultrasound parameters were tested for their incremental value to predict CAD over FRS, in each pre-test risk category. No significant difference could be appreciated between the discrimination value of FRS and Diagnostic Imaging for Coronary Artery Disease score for the presence of CAD. eCS or cPL demonstrated significant incremental prediction over FRS, consistently in the three FRS categories (P risk subjects, in whom cPL was apparently not incremental over FRS, and eCS was only of borderline significance for better discrimination. Ultrasound eCS and cPL assessments were significant predictors of angiographic CAD in patients without prior CAD but with signs or symptoms suspect for CAD, independently and incrementally to FRS, across all pre-test risk probability strata, although in high-risk subjects, only eCS maintained an incremental value. The use of cIMT was not significantly incrementally useful in any FRS risk category. Published on behalf of the

  12. Association of carotid atherosclerosis and stiffness with abdominal aortic aneurysm: The atherosclerosis risk in communities (ARIC) study.

    Science.gov (United States)

    Yao, Lu; Folsom, Aaron R; Alonso, Alvaro; Lutsey, Pamela L; Pankow, James S; Guan, Weihua; Cheng, Susan; Lederle, Frank A; Tang, Weihong

    2018-03-01

    Individuals with atherosclerosis and stiffness often have increased abdominal aortic diameters, but prospective evidence linking them to the risk of abdominal aortic aneurysm (AAA) is limited. We prospectively examined the relationship of carotid atherosclerosis and stiffness with future risk of AAA in ARIC. At Visits 1 (1987-89) or 2 (1990-1992), we assessed carotid atherosclerosis (represented by greater carotid intima-media thickness [cIMT] or presence of atherosclerotic plaque) and lower carotid distensibility (reflected by a higher carotid Beta Index). We identified incident, clinical AAAs during follow-up through 2011 using hospital discharge codes, Medicare outpatient diagnoses, or death certificates. Participants' mean age at baseline was 54.2 years (SD 5.8), 45% were male and 73% white. During a median of 22.5 years of follow-up, 542 clinical AAAs were ascertained. After multivariable adjustment, the presence of carotid atherosclerotic plaque at baseline was associated with 1.31 (95% CI: 1.10-1.57; p = 0.003) times higher risk of clinical AAA. Greater cIMT and Beta Index were also associated with clinical AAA with a dose-response across quartiles (p trend for both: 0.006; hazard ratios [95% CI] for the highest vs. lowest quartiles: 1.55 [1.13-2.11] and 1.68 [1.16-2.43], respectively). The associations of cIMT and Beta Index with AAA were independent of each other. This prospective population-based study found that indices of greater carotid atherosclerosis and lower carotid distensibility are markers of increased AAA risk. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Association of systemic inflammatory activity with coronary and carotid atherosclerosis in the very elderly.

    Science.gov (United States)

    Freitas, Wladimir M; Quaglia, Luiz A; Santos, Simone N; Soares, Alexandre A S; Japiassú, André V T; Boaventura, Vinicius; dos Santos Barros, Edilberto; Córdova, Cláudio; Nóbrega, Otávio T; Sposito, Andrei C

    2011-05-01

    To verify the existence of association between plasma levels of pro- or anti-inflammatory mediators and